Objective-To determine pharmacokinetics and tissue concentrations of azithromycin in ball pythons ( Python regius ) after IV or oral administration of a single dose. Animals-2 male and 5 female ball pythons. Procedures-Using a crossover design, each snake was given a single dose of azithromycin (10 mg/kg) IV. After a 4-week washout period, each snake was given a single dose of azithromycin (10 mg/kg) orally. Blood samples were collected prior to dose administration and 1, 3, 6, 12, 24, 48, 72, and 96 hours after azithromycin administration. Azithromycin was quantitated by use of liquid chromatography-mass spectrometry. Results-After IV administration, azithromycin had an apparent volume of distribution of 5.69 L/kg and a plasma clearance of 0.19 L/h/kg. Harmonic means for the terminal half-life were 17 hours following IV administration and 51 hours following oral administration. Mean residence times were 37 and 94 hours following IV and oral administration, respectively. Following oral administration, azithromycin had a peak plasma concentration (Cmax) of 1.04 micrograms/mL, a time to Cmax of 8.4 hours, and a prolonged mean absorption time of 57 hours. Mean oral bioavailability was 77%. Tissue concentrations ranged from 4 to 140 times the corresponding plasma concentration at 24 and 72 hours after azithromycin administration. Conclusions and Clinical Relevance-Azithromycin is well absorbed and tolerated by ball pythons. On the basis of plasma pharmacokinetics and tissue concentration data, we suggest an azithromycin dosage in ball pythons of 10 mg/kg, orally, every 2 to 7 days, depending upon the site of infection and susceptibil ity of the infective organism.

Objective-To evaluate the association between airway reactivity and age, sex, body weight, and radiographic findings in cats. Animals-32 mature cats that constituted 2 age groups (17 young cats that were 1 to 2 years old and 15 old cats that were 12 to 13 years old). Procedure-Cats were placed in the chamber of a barometric whole-body plethysmograph (volume, 38 L), and box pressure was measured at baseline and after aerosol administration of increasing concentrations of carbachol. Airway reactivity was assessed by monitoring increases in enhanced pause (PENH), a unitless variable that measures bronchoconstriction as derived from dose-response curves. The endpoint chosen was the provocative concentration of carbachol that increased PENH to 300% of the baseline value (PCPENH300). Results-We did not find a correlation between PCPENH300 and sex, body weight, number of eosinophils, PENH before bronchoconstriction, respiratory frequency, tidal volume, or minute ventilation. Airway reactivity was significantly less in the old cats (mean +/- SD PCPENH300, 0.578 +/- 0.051%), compared with the value for the young cats (0.053 +/- 0.006%). Radiographic patterns differed significantly between groups of cats; a greater proportion of old cats (12/15) had bronchointerstitial patterns, compared with the proportion of young cats (4/17). Conclusion and Clinical Relevance-These data support the notion that age exerts a strong influence on airway reactivity in adult cats, and radiographic differences suggest that structural changes in older cats may contribute to this effect. These findings have important implications for interpretation of results of airway reactivity tests in cats.

Objective-To determine the effects of immersion in warm springwater (38° to 40°C) on autonomic nervous activity in horses. Animals-10 male Thoroughbreds. Procedure-Electrocardiograms were recorded from horses for 15 minutes during a warm springwater bath after being recorded for 15 minutes during stall rest. Variations in heart rate (HR) were evaluated from the power spectrum in terms of low frequency (LF, 0.01 to 0.07 Hz) power and high frequency (HF, 0.07 to 0.6 Hz) power as indices of autonomic nervous activity. Results-Mean (+/-SE) HR during stall rest and immersion in warm springwater was 31.1 +/- 1.7 and 30.3 +/- 1.0 beat/min, respectively. No significant difference was found between the HR recorded during stall rest and that recorded during immersion in warm springwater. The HF power significantly increased from 1,361 +/- 466 milliseconds2 during stall rest to 2,344 +/- 720 milliseconds2 during immersion in warm springwater. The LF power during stall rest and immersion in warm springwater was 3,847 +/- 663 and 5,120 +/- 1,094 milliseconds2, respectively, and were not significantly different from each other. Similarly, the LF:HF ratio did not change during immersion in warm springwater. The frequency of second-degree atrioventricular block, which was observed in 2 horses, increased during immersion in warm springwater, compared with during stall rest. Conclusions and Clinical Relevance-Increases in HF power indicates that the parasympathetic nervous activity in horses increases during immersion in warm springwater. Thus, immersion in warm springwater may provide a means of relaxation for horses.

Objective-To quantitate the density of Dermatophagoides farinae and D pteronyssinus and concentrations of house dust mite (HDM) allergens (Der f 1, Der p 1, and Group 2 allergens) in the indoor microenvironment of dogs. Sample Population-50 homes in Columbus, Ohio. Procedure-In each home, samples of dust were collected from 3 locations in which dogs spent most time. Whenever possible, the species of mites collected was identified. Mite density (mites/g of dust) was assessed, and allergen concentrations were assayed by standardized ELISAs. Relative humidity and temperature in each home were monitored during a 5-day period. Characteristics of homes and sample sources were evaluated. Results-Dust samples from all 50 homes contained greater than 1 HDM allergen; Der f 1 and Der p 1 were detected in 100 and 74% of homes, respectively. Fifteen homes had HDMs; compared with D pteronyssinus, D farinae was found more commonly (14/15 homes) and at a higher density. Basements, homes without central air-conditioning, and dog beds that were greater than 1 year old had high HDM allergen concentrations. Homes with greater than 2 micrograms of Der f 1 or Group 2 allergens/g of dust or greater than 100 mites/g of dust were significantly more likely to have a maximum relative humidity greater than 75%. Conclusions and Clinical Relevance-Results indicated the presence of HDMs and HDM allergens in the specific microenvironment of dogs in homes. Factors associated with high levels of exposure were identified, which may be associated with increased risk for sensitization and development of atopic diseases.

Four different experimental models for Streptococcus suis-induced disease were compared to find a model that closely mimics naturally occurring disease in conventional pigs. Fourteen, 2-week old pigs free of S. suis type 2 were used in 2 experiments. In experiment 1, 3 pigs were inoculated intravenously (IV) and 3 pigs intranasally (IN) with S. suis. Two out of 3 of the IV-inoculated pigs exhibited signs of severe central nervous system disease (CNS) and were euthanized. Streptococcus suis type 2 was isolated from whole blood, joints, and serosal surfaces of both pigs. No clinical signs and no growth of S. suis were detected in the IN-inoculated pigs. In experiment 2, 4 pigs were inoculated IV and another 4 were inoculated IN with the same isolate as in experiment 1. One hour before inoculation the IN-inoculated pigs were given 5 mL of 1% acetic acid intranasally (IN-AA). All the IV-inoculated pigs showed CNS disease and lameness, and 2 of the pigs became severely affected and were euthanized. All the IN-AA inoculated pigs exhibited roughened hair coats and 2 pigs developed severe CNS disease and were euthanized. Streptococcus suis was isolated from the joints and blood of 3 pigs in the IV-inoculated group. Streptococcus suis was isolated from blood of 2 pigs, meninges of 3 pigs, and joints of 1 pig in the IN-AA inoculated group. Natural exposure to S. suis most likely occurs by the intranasal route. The IN-AA model should serve as a good model for S. suis-induced disease, because the natural route of exposure is intranasal and the IN-AA model was effective in inducing disease that mimics what is observed in the field.

Objective-To compare aesthesiometer-determined corneal sensitivity between diabetic and nondiabetic dogs and to investigate the correlation between corneal sensitivity and duration of diabetes or status of glycemic control, as estimated by use of glycated blood protein concentrations. Animals-23 diabetic and 29 nondiabetic normoglycemic dogs. Procedure-A Cochet-Bonnet aesthesiometer was used to measure corneal touch threshold (CTT) in 5 corneal regions of each dog. At the time of ocular examination, duration of diabetes mellitus was estimated from the history, and blood was drawn for assessment of blood glycosylated hemoglobin and serum fructosamine concentrations. Results-Median CTT for central, nasal, dorsal, temporal, and ventral corneal regions in nondiabetic dogs (1.6, 2.3, 2.8, 2.8, and 5.1 g/mm2, respectively) was significantly lower than in diabetic dogs (2.8, 4.0, 5.1, 5.1, and 6.6 g/mm2, respectively). Median regional CTT in diabetic dogs was not significantly correlated with estimated duration of diabetes mellitus or blood glycated protein concentrations. No significant difference was found in regional CTT between eyes of normoglycemic dogs with unilateral cataracts. Conclusion and Clinical Relevance-Diabetic dogs have significantly reduced corneal sensitivity in all regions, compared with nondiabetic normoglycemic dogs. Regional variation in corneal sensitivity is similar in diabetic and normoglycemic dogs. Neither glycemic control nor duration of diabetes, as estimated, is significantly correlated with corneal hyposensitivity. Corneal nerve dysfunction may be associated with recurrent or nonhealing ulcers in diabetic dogs for which no other underlying cause can be found.

Objective-To use transient and stable transfection of Chinese hamster ovary cells to clone the gene encoding feline erythropoietin (feEPO) protein, characterize the expressed protein, and assess its biological activity. Sample Population-Cultures of Chinese hamster ovary or TF-1 cells. Procedure-The gene encoding feEPO was cloned into a eukaryotic expression plasmid. Chinese hamster ovary cells were transiently or stably transfected with the plasmid. Expressed recombinant feEPO (rfeEPO) protein was purified from transiently transfected cells. The protein was characterized by use of SDS gel electrophoresis and western blot analysis. Biological activity was assessed by measuring thymidine incorporation by TF-1 erythroleukemic cells. Results-Purified rfeEPO from supernatants of transiently transfected cells was determined to be 34 to 40 kilodaltons (kd) by use of SDS gel electrophoresis, whereas the molecular weight predicted from the amino acid sequence was 21.5 kd. The banding pattern and high molecular weight suggested the protein was glycosylated. The rfeEPO proteins derived from transient or stable transfections subsequently were determined to be biologically active in vitro. Conclusions and Clinical Relevance-The gene encoding feEPO can be transfected into eukaryotic cells, and the expressed rfeEPO protein is biologically active in vitro. Cats with chronic renal failure often are anemic as a result of reduced expression of erythropoietin (EPO). Treatment with human-derived EPO stimulates RBCs in anemic cats; however, treatment is often limited by the development of antibodies directed against the recombinant human protein, which can then cross-react with endogenous feEPO. Recombinant feEPO may prove beneficial for use in cats with chronic renal failure.

Objective-To compare the minimum alveolar concentration (MAC) of isoflurane required to prevent corticocerebral activation, autonomic responses, and purposeful movements after somatic or visceral stimulation in cats anesthetized with isoflurane. Animals-17 healthy spayed female cats. Procedure-Bispectral index (BIS), autonomic parameters, and purposeful movements were monitored before and after somatic or visceral stimuli in cats anesthetized with isoflurane. End-tidal (ET) isoflurane concentration was varied to determine MAC values for cortical arousal (MACBIS), autonomic responsiveness (MACBAR), and purposeful movement (MAC). Bispectral index values greater than 60 were considered to represent corticocerebral activation. Results-Minimum alveolar concentration for purposeful movement was significantly less than MACBIS and MACBAR for both somatic and visceral stimulation. Individual MAC values for somatic stimulation were not significantly different from respective MAC values for visceral stimulation. The percentage of cats that had a BIS response greater than 60 was inversely related to the end-tidal isoflurane concentration. Conclusions and Clinical Relevance-Corticocerebral arousal and subcortical autonomic reflexes occured at isoflurane anesthetic concentrations at which reflexive or purposeful movements were absent. These results suggested that isoflurane had a preferential effect on voluntary motor output at low end-tidal isoflurane concentrations, and that sensory pathways, subcortical sympathetic output, and cortical responsiveness are less susceptible to the anesthetic effects of isoflurane. Bispectral index values obtained after somatic or visceral stimulation were sensitive for the detection of early changes in cortical excitability.

Objective-To determine whether passively acquired antibodies prevent development of a protective immune response to live virus in calves. Procedures-18 calves. Procedure-Calves were caught immediately after birth and tested free of bovine viral diarrhea virus (BVDV) and serum antibodies against BVDV. Within 48 hours, 12 calves were fed colostrum that contained antibodies against BVDV and 6 calves received BVDV antibody free milk replacer. Three milk replacer fed and 6 colostrum fed calves were exposed to virulent BVDV2-1373 at 2 to 5 weeks of life when passively acquired serum antibody titers were high. After serum antibody titers against BVDV had decayed to undetectable concentrations (at 7 to 9 months of age), the 3 remaining milk replacer fed calves, 6 colostrum fed calves previously exposed to BVDV2-1373, and 6 colostrum fed calves that had not been exposed to the virus were inoculated with BVDV2-1373. Results-Passively acquired antibodies prevented clinical disease in inoculated colostrum fed calves at 2 to 5 weeks of life. Serum antibody titers did not increase in these calves following virus inoculation, and serum antibody titers decayed at the same rate as in noninoculated colostrum fed calves. Inoculated colostrum fed calves were still protected from clinical disease after serum antibody titers had decayed to nondetectable concentrations. Same age colostrum fed calves that had not been previously exposed to the virus were not protected. Conclusion and Clinical Relevance-A protective immune response was mounted in calves with passive immunity, but was not reflected by serum antibodies titers. This finding has implications for evaluating vaccine efficacy and immune status.

Objective-To determine the influence of age on results of quantitative analysis of electromyographic (EMG) needle examination in the subclavian, triceps, and lateral vastus muscles of Dutch Warmblood horses. Animals-7 healthy young Dutch Warmblood horses (range, 13 to 18 months old), 7 healthy adult Dutch Warmblood horses (range, 4 to 10 years old), and 7 healthy elderly Dutch Warmblood horses (range, 18 to 21 years old). Procedure-An EMG needle examination was performed to evaluate insertional activity, spontaneous activity, and motor unit action potential (MUAP) variables. Although all horses were conscious, young horses were sedated prior to examination. Results-Mean insertional activity in young horses was significantly lower than in elderly horses. Pathologic spontaneous activity was rarely found in young and adult horses but was frequently evident in all muscles in all elderly horses. The MUAP duration and amplitude were significantly lower in all muscles of young horses, compared with values for adult and elderly horses. The MUAP duration and number of phases and turns were significantly lower in adult horses than in elderly horses. Group differences for percentages of polyphasic and complex MUAPs were also found. The 95% confidence intervals for MUAP duration, MUAP amplitude, and number of phases and turns for the subclavian, triceps, and lateral vastus muscles were significantly lower in young horses than in adult or elderly horses. Conclusion and Clinical Relevance-Age of the horse being examined should be considered when EMG examination is performed.