Force platform analysis of gait provides ground reaction force information that can be used to study limbs with normal or abnormal function. When combined, the interrelated variables of ground reaction forces give a more thorough description of gait than when used individually. To describe the pattern of ground reaction forces in clinically normal, conditioned, mesomorphic dogs, we studied the data from platform gait analyses of 43 dogs. Mediolateral (Fx), craniocaudal (Fy), and vertical (Fz) forces were measured and recorded. Torque (Tz) around the vertical axis also was calculated. Mean stance times for forelimbs and hind limbs were 0.278 and 0.261 second, respectively. Among dogs, ground reaction forces were normalized and expressed as percentage of body weight (%bw). The vertical (Fz) peak, average force during stance phase, and force vs time impulses were 106.68, 60.82, and 17.2 %bw in forelimbs, and were 65.11, 35.3, and 9.33 %bw in hind limbs. The forelimb braking/ propulsive (Fy) peaks were -16.74 and +6,73 %bw. In hind limbs, these peaks were -3.76 and +7.69 %bw. The usual mediolateral force (Fx) pattern found in forelimbs was laterally directed, with average peak magnitude of 6.69 %bw, whereas the hind limb patterns were variable.

Pharmacokinetics and toxicity of a single dose of doxorubicin, at dosages of 30 mg/m2 of body surface area and 1 mg/kg of body weight, were compared in 17 dogs. Effects of doxorubicin on complete blood cell count, platelet count, and the dogs' clinical condition were evaluated for 14 days. Cluster analysis, on the basis of clinical signs of doxorubicin toxicosis at the 30-mg/m2 dosage, revealed that 6 of 7 small dogs (less than or equal to 10 kg) became ill, whereas 7 of 10 large dogs (> 10 kg) remained clinically normal. Small dogs that received doxorubicin at a dosage of 30 mg/m2 had higher peak plasma concentrations, greater area under the curve for plasma drug concentration vs time, longer drug elimination half-lives, greater volumes of distribution, and more clinical signs of toxicosis than had large dogs (P less than or equal to 0.05). Five of 9 small dogs that received doxorubicin at a dosage of 30 mg/m2 developed severe myelosuppression (< 1 X 103 granulocytes/microliter). In contrast to the toxicoses with body surface area-based dosing, myelosuppression was not induced in small dogs that received doxorubicin at a dosage of 1 mg/kg. In small and large dogs given doxorubicin at a dosage of 1 mg/kg, pharmacokinetic characteristics and clinical signs of toxicosis were similar. Mean WBC counts and granulocyte counts for all dogs were lower on day 7 with 30 mg of doxorubicin/ m2 (n = 17), compared with that for 1 mg of doxorubicin/kg (n = 14; P S 0.01). This study indicated that a body weight-based (milligram per kilogram) dosing regimen may result in more uniform therapeutic and toxic responses in dogs. Limited toxicosis was observed in dogs weighing > 10 kg treated with doxorubicin with either dosing scheme; however, differences in pharmacokinetic profiles suggested that 1 mg/kg may be an inappropriately low dosage.

A commercially available automated enzyme-multiplied immunoassay technique (EMIT) was used to determine serum caffeine concentration after oral and IV administrations of caffeine at dosage of 5 mg/ kg of body weight to 12 clinically normal dogs. Dogs were allotted to 2 groups of 6 dogs each; 1 group initially received caffeine orally and the other received caffeine IV. After 72 hours, caffeine administration was repeated in all dogs in the alternate manner. Serum samples were obtained at multiple intervals over 24 hours to determine distribution and elimination kinetics. Analysis of the drug concentration-time data indicated IV elimination half-life (t1/2) of 6.39 +/- 1.87 hours, volume of distribution at steady state of 685.3 +/- 132.2 ml/kg, total body clearance of 1.31 +/- 0.38 ml/min/kg, absorption t1/2 of 1.02 +/- 0.68 hour, oral elimination t1/2 of 6.53 +/ - 2.72 hours, lag time after oral administration of 0.0614 +/- 0.0661 hour, highest measured concentration of 5.29 +/- 1.17 micrograms/ml, time to peak concentration of 2.74 +/- 1.30 hours, and bioavailability of 99.4 +/- 19.4%. Data from 6 dogs best fit a 1-compartment open model and those from 6 other dogs best fit a 2-compartment open model. On the basis of data from the 6 dogs that best fit a 2-compartment model, t1/2 of distribution was 0.58 +/- 0.72 hour. Data for oral administration best fit a single absorption phase and a single elimination phase. The increased availability and simplicity of the EMIT offers an opportunity to study the application of caffeine elimination for clinical evaluation of dogs with liver disease. Data obtained from this study allow determination of t1/2 and clearance to be simplified by obtaining samples 4 and 8 hours after oral or IV administrations and establishes canine reference values for elimination kinetics of caffeine administered at dosage of 5 mg/kg and assayed by use of the EMIT.

Five strains of Actinobacillus pleuropneumoniae serotype 1 were used to intranasally infect 5 groups of pigs. Using each bacterial strain, infected pigs (termed seeder pigs) were commingled for 48 hours with 5 groups of noninfected test pigs, then were removed. Seeder and test pigs were maintained in isolation and were observed for 14 days. Seeder pigs had mortality that was threefold greater than that of test pigs (24% vs 8%). Rectal temperature in excess of 40.3 C was achieved for 84% of test pigs and 88% of seeder pigs. Neither of these 2 variables was statistically different between the 2 groups of pigs. Clinical impression scores greater than or equal to 2 (on a 0 to 3 scale) were three-fold (64% vs 20%) greater for seeder than for test pigs (P < 0.05). The total number of bacterial isolations or nonrecoverable isolates was tabulated for test and seeder pigs' lungs at necropsy, irrespective of the amount of lesions. The number of A pleuropneumoniae isolations was not statistically different between test and seeder pig populations. Recovery of Pasteurella multocida or other bacteria was greater from the seeder pigs (P < 0.05), whereas the number of non-recoverable isolates was greater from test pigs than from seeder pigs (P < 0.05). Assessment of lung lesions at necropsy by either visual estimation or on a weight basis were in agreement. Fewer test pigs had lung lesions in excess of 5% of total lung volume than did seeder pigs (40% vs 84%) and, according to the odds ratio estimation, seeder pigs were 7 times more likely than test pigs to have such lesions. These results indicate a predictable, moderate intensity, natural exposure model for use in the study of Actinobacillus pleuropneumoniae-induced pneumonia. The seeder pig model appears to mimic field infection in development of clinical illness, febrile response, lung lesions, mortality, and low potential for secondary pneumonic bacterial involvement, thus providing a useful tool for preliminary evaluation of anti-infective modalities.

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.

The safety of moxidectin 1% injectable anthelmintic (0.6 mg/kg of body weight, 3 times the recommended dose) was evaluated in 145 reproductively sound, beef cows undergoing estrous cycle. Five treatment groups received moxidectin 1% injectable at specific times relative to a synchronized estrus (day 0): preovulatory treatment (day -2, treatment group 1), treatment at ovulation (day 0, group 2), and treatment after ovulation (days 7, 14, and 28, group 3, 4, and 5, respectively). Two groups of control cows received an injection of vehicle only at times corresponding to treatment in the other groups (6 at days -2, 7, and 28; 7 at days 0, 7, and 14). A final control group (8) received neither product or vehicle. Adverse clinical reactions were not observed in moxidectin- or vehicle-treated cows. Cows were bred by artificial insemination between days -2 and 25 and, subsequently, by breeding-sound bulls through day 65 of the study. Treatment and control groups did not differ in pregnancy rate or time to conception. Moxidectin (at 3 times the therapeutic dose) did not have deleterious effects on cow reproductive performance as examined (eg, at folliculogenesis, ovulation, and the early embryonic phase of development).

Schirmer tear test (STT), intraocular pressure (IOP) measurement, slit-lamp biomicroscopy, and indirect ophthalmoscopy were performed on 8 dogs with (13)l-induced hypothyroidism and 4 euthyroid control dogs at weeks 0, 9, 13, 17, immediately prior to treatment with levothyroxine, after 5 weeks of levothyroxine administration (0.022 mg/kg of body weight, PO, q 12 h), and at euthanasia 7 weeks after discontinuation of replacement therapy. Although the control group had higher baseline STT values than the hypothyroid group after randomization of dogs into the 2 groups (P < 0.01), STT values remained unchanged from their respective baseline values at all time intervals for both groups. Hypothyroid and control dogs had significant (P < 0.05) reduction in IOP from baseline values at all subsequent time points, but differences were not observed when hypothroid dogs were compared with controls. Goblet cell indices determined from biopsy samples of the inferior-nasal conjunctival fornix obtained before induction of hypothyroidism (baseline), immediately prior to and at conclusion of levothyroxine therapy, and at euthanasia were not significantly different when values for hypothyroid dogs were compared with their own baseline values or with values for control dogs. Histologic examination of the globes and adnexa at euthanasia also failed to indicate consistent qualitative differences between hypothyroid and control dogs. Marked reduction in serum thyroid hormone concentrations had little effect on the eye and ocular adnexa over the course of the study.

Drug-metabolizing enzyme activities were measured in livers from calves fed commercial milk replacer (nonfunctioning rumen [veal]), and those fed milk replacer supplemented with whole grain and hay from the first week of age (functioning rumen [ruminating calves]). After birth, cytochrome P450 and its NADPH-dependent reductase activities remained unchanged in veal calves; in ruminating calves they increased almost 50%. Cytochrome P450-mediated reactions, such as aniline hydroxylase activity, tripled in ruminating calves, but remained unchanged in veal calves. In both groups of calves, coumarin hydroxylase and 7-ethoxycoumarin 0-deethylase activities increased after birth, but maturation rates and activity values in ruminating calves were considerably greater than those of veal calves. The aminopyrine N-demethylase activity for veal calves was equal to that of calves with functioning rumen. Uridine diphosphoglucuronic acid glucuronyl transferase and glutathione-S-transferase activities also were higher in calves with functioning rumen than in veal calves. This increased activity in calves with functioning rumen probably represents a response to environmental exposure to xenobiotics. Compared with rumen-functional calves, bob veal (0 to 3 weeks old) and fancy veal (15 to 19 weeks old) calves fed commercial milk replacer have a significantly (P = 0.05) diminished capacity for metabolizing drugs and other xenobiotics. From a regulatory perspective, the variance in drug-metabolizing enzyme activities within these different market classes of calves suggests that specific studies designed to determine drug residue-depletion times in veal calves may be needed.

A bolus dose of methimazole (MMI) was administered IV over 1 minute to 5 healthy adult dogs at a dosage (40 mg/kg of body weight) known to impart protection against cisplatin-induced renal disease. Blood and urine samples for pharmacokinetic analysis were collected over a 24-hour period. Physical examination, CBC, determination of serum thyroid hormone concentrations, and serum biochemistry analysis were performed over a 10-day period to evaluate short-term toxicoses. At this dosage, MMI appears to be safe and well tolerated in dogs; only 1 of the 5 dogs had mild and transient increases in serum activity of hepatic enzymes. In addition, MMI did not alter serum thyroid hormone concentrations. Half-life of 8.82 hours and mean residence time of 12.18 hours were determined for MMI. Renal clearance of native MMI, along with sulfate and glucuronide conjugates, represented only 20% of total systemic clearance. Results of this study provide further information concerning clinical use of MMI in dogs and may contribute to better understanding of the mechanism of MMI protection against chemically induced nephrotoxicosis.

Although it is known that the QT interval is dependent on the preceding RR interval, QT interval does not vary during respiratory sinus arrhythmia, despite a wide variation in heart rate. To assess the rate of change of the QT interval following an abrupt increase or decrease in heart rate, QT intervals were measured from ECG of healthy, anesthetized, thoracotomized dogs in which a junctional rhythm had been induced by destroying the sinoatrial node. Atria were paced at 800- or 600-millisecond cycle durations until a steady state was reached, and then the cycle duration was changed suddenly to a new cycle duration (600 or 800 milliseconds, respectively). The time and number of heart beats required until the QT interval achieved a value of 63% (1 time constant) of the new steady state were calculated. Time constants for change in QT interval vs the number of beats following the change were 2.8 (SD = 1.3 s) seconds when heart rate was accelerated and 4.7 (SD = 2.1 s) seconds when heart rate was slowed. Differences were not statistically significant. The time constants for change in QT interval duration vs duration after the sudden change in heart rate were 1.7 (SD = 0.8 s) seconds when heart rate was accelerated and 3.7 (SD = 1.7 s) seconds when heart rate was slowed. These time constants differed significantly (P < 0.01). Response of QT interval, therefore, depended on the number of heart beats following sudden change in heart rate, but not time, except as time determined the number of heart beats. The QT interval did not change until 3 to 5 beats after the heart rate was suddenly changed. This number of beats would be more than that which would occur in 1 respiratory cycle in dogs; therefore, QT interval memory would prohibit changes in QT intervals that occur during respiratory sinus arrhythmia.