Objective-To measure concentrations of sucrose in the serum of captive dolphins after oral administration of a sucrose solution and determine the suitability of this method for use as a test to detect gastric ulcers. Animals-8 adult captive bottlenose dolphins (Tursiops truncatus). Procedures-Blood samples were collected from the ventral fluke vein of dolphins before and 45 minutes after oral administration of 500 mL of solution containing 25 or 50 g of sucrose; oral administration was achieved by use of gastric intubation. Serum was separated, diluted in a solution of 90% acetonitrile-to-10% water that contained 10 ng of an internal standard (trichlormethiazide)/microliter, mixed, and centrifuged. Supernatant was analyzed by use of liquid chromatography-mass spectrometry-mass spectrometry (LC-MS-MS). Results-Serum sucrose concentrations of dolphins were at or less than the limits of detection before oral administration. Values after administration of sucrose solution varied among dolphins and were higher and more variable after administration of 50 g, compared with concentrations after administration of 25 g. Conclusions and Clinical Relevance-Serum sucrose concentrations in samples collected during routine health evaluations of captive dolphins can be reliably measured by use of LC-MS-MS. Correlating serum sucrose concentrations with endoscopic observations of the gastric mucosa of dolphins will validate this approach for use in screening for the prevalence and severity of gastric ulcers and determining the efficacy of treatment regimens.

Objective-To study the pharmacokinetics of difloxacin (5 mg/kg) following IV, IM, and intragastric (IG) administration to healthy horses. Animals-6 healthy mature horses. Procedures-A crossover study design with 3 phases was used (15-day washout periods between treatments). An injectable formulation of difloxacin (5%) was administered IV and IM in single doses (5 mg/kg); for IG administration, an oral solution was prepared and administered via nasogastric tube. Blood samples were collected before and at intervals after each administration. A high-performance liquid chromatography assay with fluorescence detection was used to determine plasma difloxacin concentrations. Pharmacokinetic parameters of difloxacin were analyzed. Plasma creatine kinase activity was monitored to assess tissue damage. Results-Difloxacin plasma concentration versus time data after IV administration were best described by a 2-compartment open model. The disposition of difloxacin following IM or IG administration was best described by a 1-compartment model. Mean half-life for difloxacin administered IV, IM, and IG was 2.66, 5.72, and 10.75 hours, respectively. Clearance after IV administration was 0.28 L/kg.h. After IM administration, the absolute mean +/- SD bioavailability was 95.81 +/- 3.11% and maximum plasma concentration (C(max)) was 1.48 +/- 0.12 mg/L. After IG administration, the absolute bioavailability was 68.62 +/- 10.60% and C(max) was 0.732 +/- 0.05 mg/L. At 12 hours after IM administration, plasma creatine kinase activity had increased 7-fold, compared with the preinjection value. Conclusions and Clinical Relevance-Data suggest that difloxacin is likely to be effective for treating susceptible bacterial infections in horses.

Calves persistently infected (PI) with Bovine viral diarrhea virus (BVDV) represent an important source of infection for susceptible cattle. We evaluated vaccine efficacy using calves PI with noncytopathic BVDV2a for the challenge and compared tests to detect BVDV in acutely or transiently infected calves versus PI calves. Vaccination with 2 doses of modified live virus vaccine containing BVDV1a and BVDV2a protected the calves exposed to the PI calves: neither viremia nor nasal shedding occurred. An immunohistochemistry test on formalin-fixed ear notches and an antigen-capture enzyme-linked immunosorbent assay on fresh notches in phosphate-buffered saline did not detect BVDV antigen in any of the acutely or transiently infected calves, whereas both tests had positive results in all the PI calves.

The early interaction of Lawsonia intracellularis with host cells was examined with the use of porcine ileum models. Two conventional swine were anesthetized, and ligated ileum loops were prepared during abdominal surgery. The loops were inoculated with 10⁸ L. intracellularis or saline. After 60 min, samples of each loop were processed for routine histologic and electron microscopic study. Histologic and ultrathin sections of all the loops appeared normal, with no apposition of bacteria and host cells or bacterial entry events in any loop. Portions of ileum from a single gnotobiotic piglet were introduced as xenografts into the subcutis of each flank of 5 weaned mice with severe combined immunodeficiency disease. After 4 wk, 10⁸ L. intracellularis were inoculated into each of 4 viable xenografts with a sterile needle; the other 3 viable xenografts received saline. Histologic and ultrathin sections of all the xenografts 3 wk after inoculation showed relatively normal porcine intestinal architecture, with normal crypts, crypt cell differentiation, and low villous structures; the xenografts treated with the bacteria also showed intracytoplasmic L. intracellularis within crypt and villous epithelial cells. Thus, entry of L. intracellularis into target epithelial cells and multiplication may not be sufficient alone to directly cause cell proliferation. A proliferative response may require active division of crypt cells and differentiation in conjunction with L. intracellularis growth.

Objective-To evaluate canine histiocytic sarcoma cell lines and tumor samples for dysregulation of the Kit/stem-cell factor (SCF), Flt3/Flt3 ligand (Flt3L), and Met/hepatocyte growth factor (HGF) receptor tyrosine kinase signaling pathways, as these are known to contribute to the differentiation and survival of normal dendritic cells as well as malignant transformation of dendritic cells in mouse models. Sample Population-4 histiocytic sarcoma tumor cell lines and 35 formalin-fixed histiocytic sarcoma specimens obtained from dogs. Procedure-Histiocytic sarcoma cell lines were evaluated for expression of Kit/SCF, Flt3/Flt3L, and Met/HGF by use of reverse transcriptase-PCR procedures. Histiocytic sarcoma cell lines and tumor samples were evaluated for mutations in Kit, Flt3, and Met by use of PCR analysis of genomic DNA, followed by both sequencing and fluorescent PAGE for deletions or internal tandem duplications. The ability of the multitargeted split-kinase inhibitor SU11654 to block proliferation and induce apoptosis of histiocytic sarcoma cell lines was also evaluated. Results-No mutations in Kit, Flt3, and Met were identified in any of the cell lines or tumor samples evaluated. Furthermore, SU11654 did not induce cellcycle arrest or apoptosis of histiocytic sarcoma lines, even at supratherapeutic doses. Conclusions and Clinical Relevance-These data suggest that dysregulation of Kit/SCF, Flt3/Flt3L, and Met/HGF signaling pathways is unlikely to occur in histiocytic sarcomas of dogs and that inhibitors of the Kit, Flt3, and Met pathways are unlikely to provide clinical benefit to dogs with histiocytic sarcomas.

Objective-To describe a novel interlocking nail (ILN) and locking system and compare the torsional properties of constructs implanted with the novel ILN or a standard 8-mm ILN (ILN8) by use of a gap-fracture model. Sample Population-8 synthetic specimens modeled from canine tibiae. Procedures-An hourglass-shaped ILN featuring a tapered locking mechanism was designed. A synthetic bone model was custom-made to represent canine tibiae with a 50-mm comminuted diaphyseal fracture. Specimens were repaired by use of a novel ILN or an ILN8 with screws. Specimens were loaded for torsional measurements. Construct compliance and angular deformation were compared. Results-Compliance of the ILN8 was significantly smaller than that of the novel ILN. Mean +/- SD maximum angular deformation of the ILN8 construct (23.12 +/- 0.65 degrees) was significantly greater, compared with that of the novel ILN construct (9.45 +/- 0.22 degrees). Mean construct slack for the ILN8 group was 15.15 +/- 0.63 degrees, whereas no slack was detected for the novel ILN construct. Mean angular deformation for the ILN8 construct once slack was overcome was significantly less, compared with that of the novel ILN construct. Conclusions and Clinical Relevance-Analysis of results of this study suggests that engineering of the locking mechanism enabled the novel hourglass-shaped ILN system to eliminate torsional instability associated with the use of current ILNs. Considering the potential deleterious effect of torsional deformation on bone healing, the novel ILN may represent a biomechanically more effective fixation method, compared with current ILNs, for the treatment of comminuted diaphyseal fractures.

Objective-To describe the prevalence of antibodies against Salmonella spp in swine marketed in Iowa. Animals-Swine marketed by 1,044 low-volume producers and 45 high-volume producers. Procedure-Samples of diaphragm muscle collected from swine carcasses were tested by an indirect ELISA based on lipopolysaccharides from Salmonella spp, in particular Salmonella serovar Typhimurium. Prevalence of positive results for antibodies against Salmonella spp for carcasses, lots, and swine for each producer was determined. Producer-level seroprevalence was used to classify swine from producers as having negligible, low, moderate, or widespread evidence of previous or historical exposure to Salmonella spp. Results-From low-volume producers, 23,609 of 25,478 (92.7%; 95% confidence interval CI, 92.4% to 92.9%) samples had negative results, and 1,863 (7.3%; 95% CI, 7.05% to 7.56%) had antibodies against Salmonella spp. Of the 6,299 lots of swine tested, 1,191 (18.9%) contained at least 1 sample with positive results. From high-volume producers, 203 of 2,486 (8.1 %; 95% CI, 6.8% to 9.3%) samples had antibodies against Salmonella spp, and 124 of 629 lots had at least 1 sample with positive results for antibodies against Salmonella spp. Conclusions and Clinical Relevance-Less than 10% of pigs marketed in Iowa are apparently exposed to Salmonella spp. Most swine marketed by low-volume producers had negligible or little evidence of exposure to Salmonella spp, whereas a higher percentage of swine marketed by high-volume producers had positive results when tested to detect antibodies against Salmonella spp.

Objective-To quantitatively assess distraction-induced bone formation in a crural lengthening model in dogs by use of delayed-image bone scintigraphy. Animals-12 mature Labrador Retrievers. Procedure-Dogs were randomly allocated to 1 of 3 groups. A circular external skeletal fixation system was mounted on the right crus of each dog. Osteotomy of the distal portion of the tibia and fibula was performed in groups 1 and 2 and was followed by a lengthening procedure of 10 mm in the first group only. The third group served as sham-operated controls. Delayed-image bone scintigraphy with technetium-99m hydroxy methylene diphosphonate was performed 2, 4, and 6 weeks after surgery. Delayed-image-to-region-of-interest, delayed-image-to-crural, and delayed-image-to-femoral scintigraphic activity ratios were calculated. New bone formation was quantified by use of densitometric image analysis, and values for the scintigraphic ratios were compared. Results-In the distraction and osteotomy groups, delayed-image-to-region-of-interest and delayed-image-to-crural ratios increased significantly. Although densitometric image analysis revealed increased bone formation after distraction, the region-of-interest ratios and crural ratios were similar in both groups. All dogs had increased delayed-image-to-femoral ratios. Conclusions and Clinical Relevance-Delayed-image bone scintigraphy ratios were not effective at differentiating between the amounts of distraction-induced bone and osteotomy-induced bone. Metabolic bone activity in the adjacent femur was increased as a consequence of circular external skeletal fixator placement. Delayed-image bone scintigraphy was not adequately sensitive to quantitatively monitor bone formation but may be useful as an early predictor of bone healing.

Objective-To compare the urodynamic and hemodynamic effects of different dosages of phenylpropanolamine and ephedrine and determine effective dosages in increasing urethral resistance in female dogs. Animals-20 sexually intact female Beagles. Procedure-Dogs were allocated into 4 groups and received phenylpropanolamine once, twice, or 3 times daily, or ephedrine twice daily, for 14 days. On days 0, 7, and 14, urethral pressure profiles were performed while dogs were anesthetized with propofol. Variables recorded included maximum urethral pressure, maximum urethral closure pressure, integrated pressure, functional profile length, anatomic profile length, plateau distance, distance before maximum urethral pressure, and maximum meatus pressure. Arterial and central venous pressures were measured before anesthetic induction and 10 and 35 minutes after induction. Results-Administration of phenylpropanolamine once daily or ephedrine twice daily significantly increased maximum urethral pressure and maximum urethral closure pressure. Values for integrated pressure were significantly increased after 14 days of once-daily administration of phenylpropanolamine. Variables did not change significantly from day 7 to day 14. Diastolic and mean arterial blood pressures increased significantly during the treatment periods, and arterial pressure decreased during propofol infusion. Conclusions and Clinical Relevance-Oral administration of phenylpropanolamine once daily or ephedrine twice daily increased urethral resistance in clinically normal dogs and may be recommended for management of urethral sphincter mechanism incompetence. Treatment efficacy may be assessed after 1 week. Dogs with concurrent cardiovascular disease should be monitored for blood pressure while receiving alpha-adrenergic agents because of the effects on diastolic and mean arterial pressure.

During the period between January 1999 and December 2000, the distribution and seasonal patterns of Fasciola gigantica infections in cattle in the highveld and lowveld communal grazing areas of Zimbabwe were determined through monthly coprological examination. Cattle faecal samples were collected from 12 and nine dipping sites in the highveld and lowveld communal grazing areas respectively. Patterns of distribution and seasonal fluctuations of the intermediate host-snail populations and the climatic factors influencing the distribution were also determined by sampling at monthly intervals for a period of 24 months (November 1998 to October 2000) in six dams and six streams in the highveld and in nine dams in the lowveld communal grazing areas. Each site was sampled for relative snail density and the vegetation cover and type, physical and chemical properties of water, and mean monthly rainfall and temperature were recorded. Aquatic vegetation and grass samples 0-1 m from the edges of the snail habitats were collected monthly to determine the presence or absence of F. gigantica metacercariae. Snails collected at the same time were individually checked for the emergence of larval stages of F. gigantica. A total of 16 264 (calves 5 418; weaners 5 461 and adults 5 385) faecal samples were collected during the entire period of the study and 2 500 (15.4 %) of the samples were positive for F. gigantica eggs. Significantly higher prevalences were found in the highveld compared to the lowveld (P < 0.001), for adult cattle than calves ( P < 0.01) and in the wet season over the dry season (P < 0.01). Faecal egg output peaked from August / September to March / April for both years of the study. Lymnaea natalensis, the snail intermediate host of F. gigantica was recorded from the study sites with the highveld having a significantly higher abundance of the snail species than the lowveld (P < 0.01). The snail population was low between December and March and started to increase in April reaching a peak in September / October. The number of juvenile snails peaked between April and August. The mean number of snails collected was negatively correlated with rainfall and positively correlated with temperature. Mean number of snails collected was also positively correlated with Potamogeton plant species and negatively correlated with Cyperus plant species. However, none of the L. natalensis collected from the habitats were found shedding Fasciola cercariae. Metacercariae were found on herbage from the fringes of the snail habitats between February and August for both years, with most of the metacercariae concentrated on herbage 0-1 m from the banks of the habitats. Based on the findings of this study, anthelmintic treatment should be administered in December / January to control chronic and mature fasciolosis. A second treatment should be given in April / May to reduce pasture contamination and subsequently snail infection, as this is the time the snail population starts to build up. To control acute fasciolosis due to the immature liver flukes a third treatment should be given in August. The first application of molluscicides to control the snail intermediate hosts can be done in June the time when the snail is harbouring the parasite and a second application in September in order to kill new generations of infected snails.