Clinically normal dogs were evaluated in states of dehydration, euhydration, and after fluid administration to determine effects of hydration state on renal clearance values. Endogenous creatinine, exogenous creatinine, and [(14)C]inulin clearances, were determined to measure glomerular filtration rate (GFR); in some experiments p-aminohippurate clearance was determined to measure renal plasma flow. Dehydration caused significant (P < 0.05) decrease in clearance values, compared with euhydration, and clearance values during euhydration were significantly (P < 0.05) less than values obtained after a single gavage with water (30 ml/kg of body weight). Sustained administration of 3 fluid regimens was evaluated for effects on clearance values (treatment A = 30 ml of lactated Ringer's solution/kg/h; treatment B = 30 ml of water/kg by gavage hourly; treatment C = 10 ml of glucose:lactated Ringer's solution/ kg/h). All regimens of fluid therapy caused significant P < 0.05), progressive increases in GFR, but treatment C resulted in the most stable GFR values. Increases in clearance values were associated with positive fluid balance; the rate of fluid administration was greater than the rate of urine formation. Data from 285 GFR determinations on 85 dogs were evaluated retrospectively. For each determination, three 20-minute urine collections were made beginning 40 minutes after 30 mi of water/kg was given by gavage. Values between collections were significantly (P < 0.05) different, but varied by < 3%. Comparison of methods for measurement of GFR indicated that endogenous creatinine clearance and [14)C]inulin clearance were highly correlated (R(2) = 0.82), but mean clearance values were markedly different (mean +/- SEM, 28.70 +/- 0.01 and 37.07 +/- 1.29 ml/min, respectively). Exogenous creatinine clearance and [(14)C]inulin clearance were highly correlated (R(2) = 0.95), and mean values were 40.54 +/- 0.70 and 41.02 +/- 0.70 ml/min respectively. We conclude that: state of hydration has a marked effect on GFR; rate of fluid administration that exceeds rate of urine production results in progressive increases in GFR; a single water gavage of 30 ml/kg gives stable GFR values for three 20-minute collection periods, may avoid subclinical states of dehydration, and facilitates accurate urine collections; and endogenous creatinine clearance, as conducted in this study, does not accurately measure GFR.

Age, species, and disease state may substantially alter the disposition and clearance of pharmacologic agents. This is particularly important when drugs with low therapeutic index are used in ill neonates. Pharmacokinetic variables for phenylbutazone were determined in 24- to 32-hour-old healthy and endotoxemic calves after IV administration of a single dose (5 mg/kg of body weight, IV). Elimination halflife was 207 and 168 hours, and clearance was 0.708 and 0.828 ml/kg/h in healthy and endotoxemic calves, respectively. Intravenous infusion of endotoxin at the dose (2 micrograms/kg over 4 hours) given did not significantly alter any of the calculated pharmacokinetic variables. Serum thromboxane B2 concentration was significantly (P = 0.05) suppressed for 3 hours after phenylbutazone administration in healthy calves and for 4 hours in endotoxin-challenged calves. Daily administration of phenylbutazone (10 mg/kg loading, then 5 mg/kg for 9 days) to healthy and endotoxemic calves failed to induce any lesions consistent with nonsteroidal anti-inflammatory drug toxicosis.

Right dorsal colon fistulas, 2.5 cm in diameter, were created in 2 healthy ponies, using a 2-stage surgical procedure. The first stage consisted of resection of portions of the 16th and 17th ribs on the right side, followed by surgical creation of a 6- to 8-cm-diameter adhesion between the right dorsal colon and the body wall. Fistulas were created approximately 2 weeks after the first surgery by sharp dissection through the adhesion into the lumen of the colon. The fistulas have been satisfactorily maintained for > 2 years by de Pezzer catheters (45 F). Ponies with fistulas have been used for gastrointestinal experiments.

In 6 cats, mean +/- SEM baseline plasma concentrations of cortisol, corticotropin, and alpha-melanocyte-stimulating hormone (alpha-MSH) were 87 +/- 16 nmol/L, 73 +/- 14 ng/L, and 129 +/- 12 ng/L, respectively. The cats were subjected to: handling and subsequent skin testing without anesthesia; anesthesia with 50 mg of ketamine HCl and 2.5 mg of diazepam given IV, immediately followed by handling and skin testing; and anesthesia and handling as previously described, but without skin testing. Significant (P < 0.05; multivariate analysis for repeated measures) increase in plasma cortisol, corticotropin, and alpha-MSH concentrations was observed until 20 minutes after the start of the experiments in cats undergoing physical restraint and subsequent skin testing with or without preceding anesthesia. These responses were largely abolished when anesthesia with ketamine and diazepam was only followed by handling. We conclude that, during stress in cats (in contrast to dogs), the pituitary intermediate lobe is activated to secrete alpha-MSH. In addition, the cortisol response after skin testing of cats under anesthesia may be a reasonable explanation for the reported weak skin test reactivity in cats.

Characteristic alterations in the serum and urine biochemical profiles of Doberman Pinschers with congestive heart failure (CHF) resulting from idiopathic dilated cardiomyopathy were determined. We compared these alterations with those observed in 2 other models of CHF: rate overload induced by rapid ventricular pacing in dogs, and biventricular hypertrophy and dilatation induced in turkey poults by furazolidone toxicosis. Serum and urine biochemical changes in both models of CHF in dogs were mild to moderate in degree, and were moderately consistent, They could be attributed to secondary neurohumoral, hepatic, and renal effects of heart failure. The most marked and consistent changes observed were mildly decreased anion gap that developed, in part, because of decreased serum sodium concentration, moderately increased catecholamine concentrations, moderate lactaciduria, hyposthenuria, and mildly increased urea concentrations and liver enzyme activities. In birds with furazolidone cardiomyopathy, we observed mild increases in serum urate concentration, liver and muscle enzyme activities, but moderately increased sodium concentration with decreased chloride concentration. In the pacing and furazolidone models, in which CHF was rapidly induced, moderate to marked hypoproteinemia was attributable to decreases in albumin and globulin concentrations. Using the avian model we found that the hypoproteinemia could be largely attributed to blood volume expansion, and to a lesser extent, inanition. Development of hypoalbuminemia during rapid ventricular pacing and furazolidone treatment may contribute to the effects of rate overload or drug toxicity in the pathogenesis of CHF, because hypoalbuminemia may contribute to altered hemodynamics and neuroendocrine system activation. Our data indicate that clinical biochemical analysis of serum and urine may be useful for assessing progression of CHF.

Lameness examinations and radiography of the distal phalanx and associated soft-tissue structures of the front feet of 103 Thoroughbred racehorses, 4 to 9 years old, were performed to determine normal radiographic appearance and morphometry. Of 103 horses examined, 41 were used in the study that were without clinical signs of foot problems or lameness, had raced at least twice prior to radiography, and had raced at least twice more in the 6 months after radiography. Lateromedial and dorsoproximal-palmarodistal radiographic views of each front distal phalanx were used to measure 28 bone and soft-tissue structures, and to evaluate 14 radiographic findings. Significant differences were not observed between left and right digits for any radiographic determination. Mean thickness of the soft tissues dorsal to the distal phalanx, which provides an evaluation of the epidermal laminae, was 14.6 +/- 1.0 mm when measured adjacent to the distal aspect of the distal phalanx. Most horses had straight, smooth hoof walls that were parallel to the dorsal cortex of the distal phalanx. The mean degree of palmar rotation of the distal phalanx was -0.5 +/- 1.3, and none was rotated more than 4 degrees. The dorsal cortex was smooth and straight, without bone deposition or reaction in either digit for only 5 of the 41 horses. Active bone formation was seen unilaterally along the middle portion of the dorsal cortex in 7 horses, and along the distal portion of the dorsal cortex in 4 of the phalanges from 3 horses. New bone formation along the distal dorsal cortex was often accompanied by resorption of the palmar cortex. For 26 of the 31 horses without active bone deposition, smooth inactive bone formation along the midportion of the dorsal cortex was identified in 1 or both distal phalanges. Bone at the solar margin of the distal phalanx was uniformly dense and finely trabeculated, without evidence of resorption or fractures. Severe irregularity of the solar margin was not found in any digit, and the margin of both phalanges was smooth in 8 horses. Various degrees of solar margin irregularity were observed in the other 33 horses. The mean number of vascular canals within the distal phalanx was 8.4 +/- 1.7, and the diameter of the largest canal was 3.4 +/- 0.6 mm. A mean number of 2.0 +/- 1.2 vascular canals was oriented parallel to the radiographic beam on the dorsoproximal-palmarodistal view, and these were termed end-on vessels, because they were visualized as radiolucent dots greater than or equal to 1 mm in diameter in the central portion of the distal phalanx. Racing performance of horses with subtle radiographic signs of laminitis (palmar rotation, hoof wall curvature or undulations, palmar cortical resorption, distal dorsal cortical bone deposition) was poorer than that of horses without these signs. These findings are suggestive of a subclinical laminitis condition, which may influence performance without causing overt clinical signs.

An epidemiologic study of Pasteurella haemolytica serovar 1 (Ph1) in market-stressed feeder calves from 7 farms in eastern Tennessee was conducted. The nasal mucus of each calf was cultured sequentially at the farm of origin (day 0), at an auction market (day 133), and at a feedyard in Texas (days 141, 148, 155, and 169). Of the 103 calves tested, 77 were culture-positive, including 1 on day 0, 1 on day 133, 20 on day 141, 57 on day 148, 50 on day 155, and 14 on day 169. From the 143 Ph1 isolates, 20 enzyme profiles were determined by use of a commercial enzyme system that detects 19 enzymatic reactions; 4 antimicrobial susceptibility profiles were obtained, using the disk-diffusion method, which evaluated susceptibility to 11 antibacterial drugs. All isolates were positive for acid phosphatase and alkaline phosphatase, but were negative for alpha-galactosidase, alpha-mannosidase, beta-glucosidase, beta-glucuronidase, cystine aminopeptidase, N-acetyl-beta-glucosaminidase, and trypsin. Other positive enzyme reactions included: leucine aminopeptidase, 140 Ph1 isolates; phosphohydrolase, 90 isolates; alpha-fucosidase, 63 isolates; esterase (C4), 59 isolates; valine aminopeptidase, 30 isolates; esterase lipase (C8), 24 isolates; beta-galactosidase, 2 isolates; and alpha-glucosidase, chymotrypsin and lipase (C14), 1 isolate each. Thirty-four Ph1 profiles were identified, using combined enzyme and antimicrobial susceptibility profiles. The data indicate that the strains isolated during the feedyard period may have been determined more by farm of origin (P < 0.001) than by habitation with calves from other farms while in the feedyard. The combined enzyme and antimicrobial susceptibility profile method is a rapid and simple epidemiologic technique for tracking Ph1 strains in market-stressed feeder calves.

Effects of strategic anthelmintic treatment on pathophysiologic and immunologic changes induced by infection with Ostertagia ostertagi and Cooperia oncophora were studied in 2 groups, of 12 calves each: an infected group, inoculated with 200,000 mixed O ostertagi and C oncophora third-stage larvae (L3) on day 1; and an infected-treated group, similarly inoculated, but treated with ivermectin at 9 and 33 days. All calves were also inoculated at 12 weeks with Brucella abortus vaccine, at 13 weeks with bovine rhinotracheitis vaccine (bovine herpesvirus 1), and at 14 weeks with a soluble O ostertagi L3 extract, then were allowed to graze on a contaminated pasture. Four calves from each group were slaughtered at 7, 11, and 19 weeks of the study. Calves of the infected group had significantly (P < 0.05) lower weight gain than did those in the infected-treated group (60.90 kg vs 75.86 kg). They also had high plasma pepsinogen and serum gastrin values, and low serum albumin concentration from 2 or 4 weeks. Calves in the infected-treated group had steady weight gain and no significant changes in albumin and gastrin values. They also had less severe abomasal lesions and higher carcass yield. Compared with calves of the infected-treated group, those of the infected group had significantly (P < 0.05) lower blood lymphocyte reactivity to phytohemagglutinin at 14 and 16 weeks, to concanavalin A at 10 weeks, to pokeweed mitogen at 14 weeks, and to soluble O ostertagi L3 extract at 2, 4, and 14 weeks. They also had significantly (P < 0.05) lower IgG1 concentration to excretory-secretory antigens of the fourth-stage larvae of O ostertagi at 13, 18, and 19 weeks. In addition, they had significantly (P < 0.05) higher total mean eosinophil count. Antibody responses to B abortus and bovine herpesvirus 1, however, were not different between the 2 groups.

Spontaneous variations in ECG and continuous Holter monitor recordings of a colony of 31 male and 31 female cynomoigus monkeys were characterized. Electrocardiograms recorded for approximately 1 minute on 2 occasions in nonsedated monkeys were analyzed, and intervals (PR, QRS, and QT), amplitudes (P, Q, F, and T), and heart rate were determined from lead II of these tracings. In addition, Holter monitor recorders were placed on monkeys by use of carrying jackets for 16 to 24 hours of continuous recording twice during the study, and tapes were analyzed. Mean heart rate and intervals and amplitudes were similar for males and females on the first and the second recordings, Mean heart rate for males and females was 232 and 226 beats/min (bpm), respectively. The PR, QRS, and QT interval measurements, 77, 29, and 165 milliseconds, respectively, were recorded for males and 81, 30, and 162 milliseconds, respectively, were recorded for females. The P, Q, R, and T wave amplitudes were 0.16, 0.11, 0.64, and 0.28, mV respectively, for males and were 0.17, 0.10, 0.79 and 0.24 mV, respectively, for females. In addition, ventricular ectopic beats were observed in ECG from 5 females, but not in ECG from the males. Single ventricular ectopic beats were observed in 3 females for either the first or second tracing. One monkey had ectopic beats in both tracings, but in both instances, the number of ectopic beats was low (3 singles in the first and 1 in the second tracing). One monkey had runs of pairs and bigeminal beats in only the first tracing. One monkey had sporadic beats indicative of right bundle branch block morphology in both tracings. In Holter recordings, ventricular ectopic beats were identified in 47 monkeys. Ventricular ectopic beats were observed in only 1 of the 2 Holter monitor tapes for 53% of these monkeys. Most ventricular ectopic beats occurred as single beats, but pairs, ventricular tachycardia, and bigeminy also were observed. Ectopic beats were of a single morphology in 60% of the monkeys, but as many as 4 different morphologies were observed in a single tracing. Sinus arrhythmia or arrest was observed in 66% of the monkeys. Ventricular ectopic beats and sinus arrhythmia can occur without apparent cause in clinically normal monkeys. Higher prevalences of these abnormalities are identified by Holter monitoring relative to routine ECG procedures. These variables should be cautiously evaluated, because the lack of proper characterization of monkeys on test may mislead investigators as to the real importance of these findings.

Haptoglobin (HP), an acute-phase protein, is detected in serum of cows with hepatic lipidosis (fatty liver). To assess the relevance of Hp in fatty liver, induction of Hp was examined, using conditions similar to those involving development of fatty liver in cows. Induction of Hp was achieved by a combination of dexamethasone administration (0.1 mg/kg of body weight) and 2 days' starvation. Haptoglobin appearance in serum was not associated with the increase of alpha 1-acid glycoprotein (a marker for inflammation). This treatment increased serum nonesterified fatty acids concentration and decreased serum triglycerides concentration. Protein kinase C activity was decreased in the cytosolic fractions of liver and mononuclear cells. Reduction of protein kinase C-catalyzed endogenous protein phosphorylation also was observed, particularly in the cytosolic fractions of the tissue and cells. Detection of Hp in serum of cows with fatty liver appears to be explained by the fact that Hp is induced by dexamethasone administration and starvation, which are similar to the condition responsible for fatty liver development. The change of protein kinase C-catalyzed phosphorylation was suggested to be involved in the induction of Hp in cows.