Vestibulotoxic and ototoxic effects often are seen after long-term, high-dose systemic treatment with gentamicin, but toxic effects after topical use have not been reported in animals, to the authors' knowledge. Vestibular and auditory effects of twice daily otic gentamicin treatment for 21 days were evaluated in 10 dogs with intact tympanic membranes and in the same 10 dogs after experimental bilateral myringotomy. Each dog served as its own control; 7 drops of gentamicin sulfate (3 mg/ml in a buffered aqueous vehicle) were placed in 1 ear, and 7 drops of vehicle were placed in the opposite ear. Treatment and control ears were reversed after myringotomy. Vestibular function was evaluated daily by neurologic examination and behavioral assessment Auditory function was evaluated twice weekly by determination of brain stem auditory evoked potentials. Gentamicin sulfate placed in the ear of clinically normal dogs with intact or ruptured tympanic membranes, in the quantities used in this study, did not induce detectable alteration of cochlear or vestibular function. Serum gentamicin concentration after 21 days of treatment was detectable in only 2 dogs and was an order of magnitude below documented toxic concentrations.

Because caffeine is metabolized by the hepatic P-450 cytochrome oxidase system, clearance of caffeine is an excellent quantitative test of hepatic function in human beings. It is currently used in much the same way that creatinine clearance is used to assess renal function. Caffeine clearance was measured in lactating dairy cows initially to determine the suitability of caffeine clearance as an indicator of hepatic function in cattle. Pharmacokinetic variables of caffeine were studied in 6 adult lactating dairy cows after IV administration of a single dose of caffeine sodium benzoate (2 mg of caffeine/kg of body weight). Caffeine concentration was analyzed by use of an automated enzyme immunoassay. The lower limit of detection of the assay for caffeine in serum was 0.079 micrograms/ml. Serum caffeine concentration-time curves best fit an open two-compartment pharmacokinetic model. Harmonic mean elimination half-life was 3.8 (range, 2.6 to 6.9) hours, and total clearance was 0.118 (range, 0.090 to 0.197) L/kg/h. Milk caffeine concentration was similar to serum concentration 1.5 to 24 hours after caffeine administration. Adverse effects were not observed in cows given caffeine.

Immunoglobulin E is produced in response to parasitic nematodes that undergo blood and tissue migrations. Results of our previous studies indicated that IgE and IgG respond to Dirofilaria immitis in experimentally infected dogs. To determine the association between treatment with the larvicide, diethylcarbamazine (DEC), and antibody responses and to examine the potential influence of infection with a nonfilarid intestinal nematode on isotype-specific immune responses, we monitored, by use of isotype-specific ELISA, separate IgE and IgG responses against D immitis in 4 groups (A-D) of 8 dogs experimentally coinfected with D immitis and Ancylostoma caninum. All dogs were monitored from 2 weeks before inoculation with D immitis, through postinoculation (PI) week 20. Group-B dogs received a daily regimen of 6.6 mg of DEC/kg of body weight. Group-C dogs received 4.95 mg of oxibendazole/kg daily. Group-D dogs received DEC and oxibendazole, equivalent to the daily doses given to dogs of groups B and C. All dogs given oxibendazole had no A caninum at necropsy. Of the groups receiving DEC, 3 group-B dogs each had 1 to 2 D immitis at necropsy. When results of chronologic IgE determination for all groups were statistically compared, only groups B and C had significant (P = 0.0148 and P << 0.00005, respectively) increases in IgE values. Group-C dogs had the highest IgE values from PI week 10 until the end of the study, whereas IgG values were statistically identical to those of group-A dogs. Group-B dogs given only DEC and having the least number of D immitis of all groups, had IgE values that peaked at PI week 6; values were significantly (P = 0.0002) higher than those for all other groups. In Group-B dogs, IgG values increased significantly (P << 0.00005) only at PI week 20 and were significantly (P << 0.00005) decreased after PI week 6, compared with values for all other groups. Group D containing 6 dogs infected with 1 to 18 D immitis found at necropsy had IgE values between those of group-B dogs and those of non-DEC-treated groups at PI week 6. There was no difference in IgG values between 3 groups at PI week 6, and IgE values were found to be a better correlator than were IgG values to the number of D immitis larvae killed in the tissues during this period. All differences in IgG and IgE values not only correlated with treatment status and number of D immitis adults found at necropsy, but also with the developmental stage of D immitis commonly present in the groups at each time point and the number of adult D immitis found at necropsy.

The percentage of limb contact time spent in braking and propulsion was determined for the forelimbs and hind limbs of Greyhounds at 2 walk speeds and 3 trot speeds. Limb contact times decreased significantly (P < 0.05) as velocity increased between each velocity range. At a slow walk (0.92 to 1.03 m/s), braking and propulsion were 56.1 and 43.6% of contact time in the forelimbs and 41.6 and 58.1% of contact time in the hind limbs, respectively. At a fast walk (1.06 to 1.17 m/s), braking and propulsion were 56.7 and 43.5% of contact time in the forelimbs and 41.5 and 58.4% of contact time in the hind limbs, respectively. There was no significant difference in the percentage of contact time that the forelimbs and hind limbs spent in braking and propulsion between the 2 walk velocities. At the slow trot (1.5 to 1.8 m/s), braking and propulsion were 56.8 and 43% of contact time in the forelimbs and 30.1 and 67.6% of contact time in the hind limbs, respectively. At the medium trot (2.1 to 2.4 m/s), braking and propulsion were 55.9 and 43.5% of contact time in the forelimbs and 33.8 and 63.2% of contact time in the hind limbs, respectively. At the fast trot (2.7 to 3.0 m/s), braking and propulsion were 57.2 and 43% of contact time in the forelimbs and 37.5 and 61.1% of contact time in the hind limbs, respectively. Braking percentage increased and propulsive percentage decreased significantly (P < 0.05) in the hind limbs between the slow and fast trot speeds. There was no significant difference in the percentage of forelimb contact time spent in braking and propulsion between the walk and the trot gaits or among the 3 trot velocities.

Intraocular pressure (IOP) was measured by use of Mackay-Marg applanation tonometry in 8 normal, manometrically controlled, enucleated, canine eyes with and without 1 of 2 piano therapeutic soft contact lenses (1 and 2) covering the cornea. Differences were not significant between measurements made without a contact lens and those made through either lens at manometer IOP < 30 mm of Hg. At manometer IOP greater than or equal to 30 mm of Hg, use of a contact lens tended to result in a statistically greater (P < 0.05) estimate of IOP than when a lens was not used. This difference, however, achieved only a maximum of 2.6 mm of Hg at the 80 mm of Hg value, and was not regarded as clinically important. Measurements obtained through lens 1 were not significantly different from those obtained through lens 2. The IOP can be accurately estimated in dogs; using the Mackay-Marg tonometer, without removing either type of bandage soft contact lens, thereby avoiding potential disruption of an already compromised cornea.

Reference values for hematologic variables change with increasing age in cattle. Therefore, the purpose of the study reported here was to describe the peritoneal fluid constitutents of clinically normal young calves, and to compare cellular concentration and distribution in blood and peritoneal fluid of young calves with those of adult cattle. Eight healthy 8-week-old male Holstein calves and 8 healthy 3- to 8-year-old Holstein cows were studied. Peritoneal fluid was collected from calves along the ventral midline, 4-cm cranial to the umbilicus. Abdominocentesis was performed in the region of the lower right flank in adult cattle. Correlation analysis, using the Pearson's correlation coefficient, and regression analysis were performed for blood and peritoneal fluid data from calves. Data from calves were compared with those of cows, using Wilcoxon's rank sum test. A P value < 0.05 was considered significant for all tests. Calves had significantly lower blood eosinophil count (P < 0.003) and plasma protein concentration (P < 0.001) than did cows. Calves had significantly higher peritoneal fluid nucleated cell (P < 0.05) and mononuclear cell (P < 0.05) counts, but lower peritoneal fluid eosinophil cell count (P < 0.003) than did cows. For calves, nulceated cell and lyhocyte cell counts in the blood had a high, positive correlation with those of peritoneal fluid. However, the prediction equation for nucleated cell count accounted for a modest proportion of variability. A prediction equation for peritoneal fluid lymphocyte cell count was established. On the basis of results of this study, reference ranges established for peritoneal fluid constituents of clinically normal adult cattle may not be appropriate for interpretation of peritoneal fluid analysis of calves.

A matched case-control study design was used to assess the effects of long-term administration of a prolonged release formulation of bovine somatotropin (sometribove) on clinical lameness and limb lesions in dairy cows. Cows treated with sometribove for at least 2 lactations (cases) and nontreated dairy cows matched by herd, parity, age, and stage of lactation (controls) in 8 herds were evaluated for clinical lameness (as assessed by gait abnormality) and limb lesions by 2 observers, using a standardized scoring procedure at a single herd visit. Although a high proportion of the study cows were clinically lame (43%), an association was not detected between chronic administration of sometribove and prevalent lameness. Of 21 types of limb lesions identified, 2 were positively associated and 2 were negatively associated with long-term sometribove use. Superficial laceration of the tarsus (odds ratio [OR] = 2.1) and superficial swelling of the metatarsophalangeal joint (OR = 4.5) were positively associated with sometribove treatment, whereas femoral lesions (OR = 0.2) and superficial lacerations of the femur (OR = 0.14) were negatively associated with sometribove treatment.

Ultrasonographic cross-sectional area (CSA) measurements of equine superficial digital flexor (SDF) tendon were obtained to determine the feasibility of ultrasonography for CSA measurement of tendon in vivo and in vitro. Ultrasonographic measurements were compared with a more traditional CSA measurement method, ink-blot analysis. In addition, values for ultrasonographic SDF tendon mean echogenicity were obtained in vivo and in vitro. The left forelimb SDF tendons of 23 horses were evaluated ultrasonographically. Cross-sectional images were acquired at 4-cm intervals distal to the base of the accessory carpal bone (DACB) to the level of the proximal sesamoid bones while horses were standing squarely. After euthanasia, the left forelimbs were mounted in a materials testing system (MTS) and loaded under tension to standing load. Ultrasonographic images were again acquired at the same locations. The ultrasonographic images were digitized, and values for ultrasonographic CSA and mean echogenicity were obtained for each level. Immediately after mechanical testing, a 1-cm-thick transverse section of SDF tendon at 12 cm DACB was removed. Three ink blots were prepared from each end of the removed tendon section and digitized. The 6 CSA values were averaged to generate a value for morphologic CSA for each SDF tendon at 12 cm DACB. Standing ultrasonographic tendon CSA at 12 cm DACB was consistently smallest (mean +/- SD CSA = 86 +/- 11 mm2), followed by MTS ultrasonographic CSA (mean, 95 +/- 12 mm2), with ink-blot morphologic CSA being largest (mean, 99 +/- 15 mm2). Comparison of standing and MTS ultrasonographic values at 12 cm DACB revealed a strong positive linear correlation between methods (R2 = 0.74, P = 0.001). Comparison of ink-blot CSA at 12 cm DACB with standing and MTS ultrasonographic CSA revealed strong positive linear correlations (R2 = 0.64, P = 0.001 and R2 = 0.72, P = 0.001, respectively). For ultrasonographic mean echogenicity, standing values insignificantly exceeded MTS values at each level. The authors conclude that ultrasonography is a useful technique for the noninvasive assessment of SDF tendon CSA that can be applied in vivo and in vitro.

Starling forces and hemodynamics in the digits of 5 horses were studied during early laminitis induced by oral administration of an aqueous extract of black walnut (Juglans nigra). The black walnut extract was prepared from heartwood shavings and was administered by nasogastric tube. Heart and respiratory rates, rectal temperature, central venous and arterial pressures, digital pulses, and signs of lameness were monitored. Blood samples were collected for determination of WBC count, hemoglobin concentration, and PCV and for endotoxin and tumor necrosis factor assays. Total WBC count and central venous pressure were monitored until they decreased by 30 or 20%, respectively. These decreases in WBC count and central venous pressure were observed 2 to 3 hours after dosing with black walnut extract. Respiratory and heart rates, body temperature, systolic and diastolic blood pressures, PCV, and hemoglobin concentration did not change significantly. Anesthesia was induced, heparin (500 IU/kg of body weight) was administered IV, and a pump-perfused extracorporeal digital preparation was established. Digital arterial and venous pressures were maintained at 100 and 30 mm of Hg, respectively. Blood flow, capillary pressure, lymph and plasma protein concentrations, and weight of the isolated digit during rapid increase in venous pressure were measured. Isogravimetric capillary filtration coefficient, vascular compliance, vascular and tissue oncotic pressures, tissue pressure, osmotic reflection coefficient, and precapillary and postcapillary resistances were calculated. Mean digital blood flow was 14 ml/min/100 g, capillary pressure was 52 mm of Hg, and vascular compliance was 0.06 ml/mm of Hg. The vascular and tissue oncotic pressures were 21.49 and 4.93 mm of Hg, respectively. The osmotic reflection coefficient was 0.71, and tissue pressure was 41 mm of Hg. The precapillary and postcapillary resistances were 7 and 2 mm of Hg/ml, respectively. Capillary permeability to proteins was not significantly different from that previously measured in healthy horses, suggesting that the increased capillary filtration coefficient reflected increased capillary hydrostatic pressure and perfusion of previously nonperfused capillaries. Neither endotoxin nor serum tumor necrosis factor activity was detected in any samples. The hemodynamic and Starling forces observed in this study were similar to those observed after laminitis was induced by administration of a carbohydrate gruel. Significant differences between the 2 models were detected for total vascular resistance, postcapillary resistance, and capillary filtration coefficient. It is likely that these differences were identified because the horses administered the black walnut extract were at an earlier stage in the disease process. The findings of this study suggest that the increase in capillary pressure causes transvascular fluid movement, resulting in increased tissue pressure and edema. We hypothesize that further increases in tissue pressure may collapse capillary beds and lead to tissue ischemia.

Twenty-four horses were randomly allocated to 3 groups. All horses underwent a ventral midline celiotomy, and the large colon was exteriorized and instrumented. Group-1 horses served as sham-operated controls, group-2 horses underwent 6 hours of colonic ischemia, and group-3 horses were subjected to 3 hours of ischemia and 3 hours of reperfusion. Baseline blood samples were collected, then low-flow colonic ischemia was induced in horses of groups 2 and 3 by reducing colonic arterial blood flow to 20% of baseline. All horses were monitored for 6 hours. Citrated systemic venous (SV) blood samples were collected from the main pulmonary artery, and colonic venous (CV) samples were collected from the colonic vein draining the ventral colon. Samples were collected at 0, and 2, 3, 3.25, 4, and 6 hours for determination of one-stage prothrombin time, activated partial thromboplastin time, antithrombin III activity, and fibrinogen concentration. Data were analyzed statistically, using two-way ANOVA for repeated measures, and post-hoc comparisons were made by use of Student Newman Keul's test. Statistical significance was set at P < 0.05. There were significant decreases in all hemostatic variables by 2 hours in SV and SV samples from horses of all 3 groups, but there were no differences among the 3 groups for any of these variables. These hemostatic alterations could have been secondary to a hypercoagulable state or to fluid therapy-induced hemodilution. Colonic ischemia-reperfusion was not the cause of these alterations because these alterations also were observed in the sham-operated control horses. Significant temporal alterations existed even after accounting for the hemodilution. The most plausible explanation for these alterations is that hemostatic activation was incited by the celiotomy and manipulation of the colon during exteriorization and instrumentation. Comparison of paired SV and CV samples for each hemostatic variable revealed significant differences for the absolute values of one-stage prothrombin time and fibrinogen concentration, but not for activated partial thromboplastin time or antithrombin III activity. This indicates that monitoring SV hemostatic variables does not necessarily provide an accurate assessment of hemostatic function in regional vascular beds. Large-colon ischemia with or without reperfusion did not alter hemostatic function.