Objective-To determine expression of folate receptors (FRs) and folate uptake in multicentric lymphomas in dogs. Sample-10 dogs with histopathologically confirmed multicentric lymphoma and 20 archival lymph node biopsy specimens from dogs with multicentric lymphoma. Procedures-Multicentric lymphomas in 10 dogs were prospectively evaluated for FR expression by use of immunohistochemical analysis and for in vivo folate uptake by use of nuclear scintigraphy. Dogs with FR-expressing tumors were eligible for FR-targeted chemotherapy. Twenty archival lymphoma biopsy specimens were also evaluated with immunohistochemical analysis. Results-FRs were not detected with immunohistochemical analysis in lymph node samples obtained from the 10 dogs or in archival biopsy specimens. However, nuclear scintigraphy revealed uptake of radioactive tracer in 6 of 10 dogs. Five of these 6 dogs were treated with an FR-targeted chemotherapeutic agent; results of treatment were complete remission in 1 dog, stable disease in 2 dogs, and progressive disease in 2 dogs. Treatment-related toxicoses generally were mild. Conclusions and Clinical Relevance-This study provided strong evidence for folate uptake in a substantial portion of multicentric lymphomas of dogs and indicated the antitumor activity of FR-targeted chemotherapeutics for these cancers. Use of FR-targeted chemotherapeutics may be promising for the treatment of FR-expressing multicentric lymphomas in dogs. Further studies are needed to determine reasons for lack of immunoreactivity to currently identified anti-FR antibodies and to develop improved methods for detecting FRs in lymphomas of dogs.

Objective- To evaluate anatomic landmarks to define the ideal suture placement location to achieve appropriate and consistent arytenoid cartilage abduction via unilateral cricoarytenoid lateralization (UCL) in dogs. Sample- 6 cadaveric canine larynges. Procedures- Laryngeal airway resistance (LAR) was determined for each specimen before (baseline) and after suture placements with the epiglottis open and closed. To achieve UCL, suture was placed through the cricoid cartilage just caudal to the cricoarytenoid articulation (suture placement position [SPP] 1), one-fourth of the distance caudally between the cricoarytenoid and cricothyroid articulations (SPP 2), and three-fourths of the distance caudally between the cricoarytenoid and cricothyroid articulations (SPP 3). The LAR was again calculated after tensioning of each suture separately. Results- With a closed epiglottis, median LAR was 30.0, 20.4, 11.4, and 3.3 cm H2O/L/s at baseline and SPPs 1, 2, and 3, respectively. After UCL at SPP 1, LAR with the epiglottis closed was not significantly different from that at baseline. With an open epiglottis, median LAR was 2.0, 0.4, 0.2, and 0.0 cm H(2)O/L/s at baseline and SPPs 1, 2, and 3, respectively. After UCL at SPPs 1, 2, or 3, LAR with an open epiglottis was significantly lower than that at baseline. Conclusions and Clinical Relevance- Results indicated that placement of suture through the cricoid cartilage at the caudal border of the cricoarytenoid articulation was appropriate to sufficiently reduce LAR without increasing the risk of aspiration pneumonia through overabduction of the arytenoid cartilage.

Objective-To investigate age-related and regional differences in estimated metabolite concentrations in the brain of healthy dogs by means of magnetic resonance spectroscopy (MRS). Animals-15 healthy Beagles. Procedures-Dogs were grouped according to age as young (n = 5; all dogs were 2 months old), adult (5; mean age, 4.5 years), or geriatric (5; all dogs were 12 years old). Imaging was performed by use of a 1.5-T MRI system with T1- and T2-weighted spin-echo and fluid-attenuated inversion recovery sequences. Signal intensity measurements for N-acetyl aspartate, creatine, choline, and lactate-alanine (the spectroscopic peaks associated with alanine and lactate could not be reliably differentiated) were determined with MRS, and areas under the spectroscopic peaks (representing concentration estimates) were calculated. Ratios of these metabolite values were compared among age groups and among brain regions with regression analysis. Results-The choline-to-creatine ratio was significantly higher in young dogs, compared with other age groups. The N-acetyl aspartate-to-choline ratio was significantly lower in young dogs and geriatric dogs than in adult dogs. When all age groups were considered, the choline-to-creatine ratio was significantly higher and N-acetyl aspartate-to-choline ratio was significantly lower in the frontal lobe than in all other regions. The N-acetyl aspartate-to-creatine ratio was significantly lower in the cerebellum than in other regions. Conclusions and Clinical Relevance-Metabolite ratios varied significantly among age groups and brain regions in healthy dogs. Future studies should evaluate absolute concentration differences in a larger number of dogs and assess clinical applications in dogs with neurologic diseases.

This study aimed to investigate and compare the antagonistic effects of atipamezole, yohimbine, and prazosin on xylazine-induced diuresis in clinically normal cats. Five cats were repeatedly used in each of the 9 groups. One group was not medicated. Cats in the other groups received 2 mg/kg BW xylazine intramuscularly, and saline (as the control); 160 mg/kg BW prazosin; or 40, 160, or 480 mg/kg BW atipamezole or yohimbine intravenously 0.5 h later. Urine and blood samples were collected 10 times over 8 h. Urine volume, pH, and specific gravity; plasma arginine vasopressin (AVP) concentration; and creatinine, osmolality, and electrolyte values in both urine and plasma were measured. Both atipamezole and yohimbine antagonized xylazine-induced diuresis, but prazosin did not. The antidiuretic effect of atipamezole was more potent than that of yohimbine but not dose-dependent, in contrast to the effect of yohimbine at the tested doses. Both atipamezole and yohimbine reversed xylazine-induced decreases in both urine specific gravity and osmolality, and the increase in free water clearance. Glomerular filtration rate, osmolar clearance, and plasma electrolyte concentrations were not significantly altered. Antidiuresis of either atipamezole or yohimbine was not related to the area under the curve for AVP concentration, although the highest dose of both atipamezole and yohimbine increased plasma AVP concentration initially and temporarily, suggesting that this may in part influence antidiuretic effects of both agents. The diuretic effect of xylazine in cats may be mediated by a2-adrenoceptors but not a1-adrenoceptors. Atipamezole and yohimbine can be used as antagonistic agents against xylazine-induced diuresis in clinically normal cats.

Retinoids play an important role in lung development and immune response. The effects of retinoids are mediated through 2 families of retinoid receptors: retinoic acid receptors (RARs) and retinoid X receptors (RXRs), with alpha (α), beta (β), and gamma (γ) subtypes in each family. To date, no data exist on the expression pattern of retinoid receptors in lungs of cattle, dogs, and pigs. Because of the biomedical importance of retinoid receptors in inflammation and immune responses, Western blot, immunohistology, and immunoelectron microscopy were used to determine the expression of retinoid receptors in normal lungs of cattle, dogs, and pigs (n = 2 for each species). Western blot showed expression of all 6 retinoid receptor subtypes in pig lungs. Immunohistology data indicated differential expression of retinoid receptors in airway epithelium, vascular endothelium, alveolar/septal macrophages, and alveolar septum in all 3 species. Electron microscopy showed nuclear localization of retinoid receptors in neutrophils and pulmonary intravascular macrophages. Retinoic acid receptors (RAR) α subtype were localized in cytoplasmic vacuoles of pig monocytes. These data indicate constitutive expression of retinoid receptors in the lungs of cattle, dogs, and pigs.

Macrophages function as phagocytes and antigen-presenting cells in the body. As has been demonstrated in mammals, administration of clodronate [dichloromethylene bisphosphonate (Cl 2MBP)] encapsulated liposomes results in depletion of macrophages. Although this compound has been used in chickens, its effectiveness in depleting macrophages has yet to be fully determined. Here, we show that a single administration of clodronate liposomes to chickens results in a significant depletion of macrophages within the spleen and lungs of chickens up to 4 d post-treatment. This finding suggests that, in order to obtain depletion of macrophages in chickens for greater than 5 d, it is necessary to administer clodronate liposomes 4 d apart. The study also showed that 2 treatments of clodronate liposomes at 4-day intervals resulted in the depletion of macrophages for up to 10 d. The findings of the present study will encourage more precise studies to be done on the potential roles of macrophages in immune responses and in the pathogenesis of microbial infections in chickens.

Objective- To compare accuracy of a noninvasive single-plane fluoroscopic analysis technique with radiostereometric analysis (RSA) for determining 3-D femorotibial poses in a canine cadaver stifle joint treated by tibial-plateau-leveling osteotomy (TPLO). Sample- Left pelvic limb from a 25-kg adult mixed-breed dog. Procedures- A CT scan of the left pelvic limb was performed. The left cranial cruciate ligament was transected, and a TPLO was performed. Radiopaque beads were implanted into the left femur and tibia, and the CT scan was repeated. Orthogonal fluoroscopic images of the left stifle joint were acquired at 5 stifle joint flexion angles ranging from 110° to 150° to simulate a gait cycle; 5 gait cycles were completed. Joint poses were calculated from the biplanar images by use of a digitally modified RSA and were compared with measurements obtained by use of hybrid implant-bone models matched to lateral-view fluoroscopic images. Single-plane measurements were performed by 2 observers and repeated 3 times by the primary observer. Results- Mean absolute differences between results of the single-plane fluoroscopic analysis and modified RSA were 0.34, 1.05, and 0.48 mm for craniocaudal, proximodistal, and mediolateral translations, respectively, and 0.56°, 0.85°, and 1.08° for flexion-extension, abduction-adduction, and internal-external rotations, respectively. Intraobserver and interobserver mean SDs did not exceed 0.59 mm for all translations and 0.93° for all rotations. Conclusions and Clinical Relevance- Results suggested that single-plane fluoroscopic analysis by use of hybrid implant-bone models may be a valid, noninvasive technique for accurately measuring 3-D femorotibial poses in dogs treated with TPLO.

Objective-To develop a method for experimental induction of equine rhinitis A virus (ERAV) infection in equids and to determine the clinical characteristics of such infection. Animals-8 ponies (age, 8 to 12 months) seronegative for antibodies against ERAV. Procedures-Nebulization was used to administer ERAV (strain ERAV/ON/05; n = 4 ponies) or cell culture medium (control ponies; 4) into airways of ponies; 4 previously ERAV-inoculated ponies were reinoculated 1 year later. Physical examinations and pulmonary function testing were performed at various times for 21 days after ERAV or mock inoculation. Various types of samples were obtained for virus isolation, blood samples were obtained for serologic testing, and clinical scores were determined for various variables. Results-ERAV-inoculated ponies developed respiratory tract disease characterized by pyrexia, nasal discharge, adventitious lung sounds, and enlarged mandibular lymph nodes. Additionally, these animals had purulent mucus in lower airways up to the last evaluation time 21 days after inoculation (detected endoscopically). The virus was isolated from various samples obtained from lower and upper airways of ERAV-inoculated ponies up to 7 days after exposure; this time corresponded with an increase in serum titers of neutralizing antibodies against ERAV. None of the ponies developed clinical signs of disease after reinoculation 1 year later. Conclusions and Clinical Relevance-Results of this study indicated ERAV induced respiratory tract disease in seronegative ponies. However, ponies with neutralizing antibodies against ERAV did not develop clinical signs of disease when reinoculated with the virus. Therefore, immunization of ponies against ERAV could prevent respiratory tract disease attributable to that virus in such animals.

Objective- To assess the accuracy of an ultrasound velocity dilution cardiac output (UDCO) method, compared with that of the lithium dilution cardiac output (LiDCO) method, for determination of cardiac output (CO) in juvenile horses with experimentally induced hypovolemia. Animals- 12 anesthetized 2- to 6-month-old horses. Procedures- For each anesthetized horse, CO was determined by the LiDCO and UDCO methods prior to any intervention (baseline state), after withdrawal of approximately 40% of the horse's blood volume (low CO state), after maintenance of hypovolemia and infusion of norepinephrine until mean arterial blood pressure was equal to baseline value (high CO state), and after further infusion of norepinephrine and back-transfusion of withdrawn blood (posttransfusion state). For each of the 4 hemodynamic situations, CO and calculated cardiac index (CI) values were obtained by each method in duplicate (8 pairs of measurements/horse); mean values for each horse and overall mean values across all horses were calculated. Agreement between CI determined by each method (96 paired values) was assessed by Bland-Altman analysis. Results- For the UDCO method–derived CI measurements among the 12 horses, mean ± SD bias was −4 ± 11.3 mL/kg/min (95% limits of agreement, −26.1 to 18.2 mL/kg/min) and mean relative bias was −10.4 ± 21.5% (95% limits of agreement, −52.6% to 31.8%). Conclusions and Clinical Relevance- Results indicated that, compared with the LiDCO method, the UDCO method has acceptable clinical usefulness for determination of CO in foals.

Objective- To determine the pharmacokinetics of hydromorphone hydrochloride after IV and IM administration in American kestrels (Falco sparverius). Animals-12 healthy adult American kestrels. Procedures- A single dose of hydromorphone (0.6 mg/kg) was administered IM (pectoral muscles) and IV (right jugular vein); the time between IM and IV administration experiments was 1 month. Blood samples were collected at 5 minutes, 1 hour, and 3 hours (n = 4 birds); 0.25, 1.5, and 9 hours (4); and 0.5, 2, and 6 hours (4) after drug administration. Results- Plasma hydromorphone concentrations were determined by means of liquid chromatography with mass spectrometry, and pharmacokinetic parameters were calculated with a noncompartmental model. Mean plasma hydromorphone concentration for each time was determined with naïve averaged pharmacokinetic analysis.Plasma hydromorphone concentrations were detectable in 2 and 3 birds at 6 hours after IM and IV administration, respectively, but not at 9 hours after administration. The fraction of the hydromorphone dose absorbed after IM administration was 0.75. The maximum observed plasma concentration was 112.1 ng/mL (5 minutes after administration). The terminal half-life was 1.25 and 1.26 hours after IV and IM administration, respectively. Conclusion and Clinical Relevance- Results indicated hydromorphone hydrochloride had high bioavailability and rapid elimination after IM administration, with a short terminal half-life, rapid plasma clearance, and large volume of distribution in American kestrels. Further studies regarding the effects of other doses, other administration routes, constantrate infusions, and slow release formulations on the pharmacokinetics of hydromorphone hydrochloride and its metabolites in American kestrels may be indicated..