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- Author or Editor: G. L. Murphy x
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Abstract
OBJECTIVE
Describe the pharmacokinetics of grapiprant administered orally with food to red-tailed hawks (RTHAs; Buteo jamaicensis) and compare the results with previously described grapiprant pharmacokinetics administered without food in this species.
ANIMALS
6 healthy adult RTHA (3 males, 3 females) under human care.
PROCEDURES
A single dose of grapiprant (30 mg/kg) was given orally to RTHAs, followed by force-feeding. Blood samples were obtained at 14 time points for 120 hours postgrapiprant administration. Plasma concentrations of grapiprant were measured via tandem liquid chromatography-mass spectrometry. Nonparametric superimposition using pharmacokinetic modeling software used plasma concentrations to calculate simulations of grapiprant plasma concentrations for 30 mg/kg administered orally with food every 12 hours.
RESULTS
The arithmetic mean maximum plasma concentration was 405.8 ng/mL, time to maximum plasma concentration was 16 hours, and harmonic mean terminal half-life was 15.6 hours. Simulations determined 30 mg/kg every 12 hours could attain minimum effective concentrations (> 164 ng/mL) reported in dogs for a sustained period of approximately 20 hours.
CLINICAL RELEVANCE
Grapiprant plasma concentrations were achieved above the canine therapeutic concentrations within 16 hours postmedication. Mean concentrations were maintained for approximately 20 hours. Simulations support a dosing frequency of 12-hour intervals with food reaching minimum effective concentrations established for canines, although it is unknown whether these plasma concentrations are therapeutic for birds. Bioaccumulation was not noted on simulations secondary to increased grapiprant administration. Further research including multidose assessments at this current dose with food, in vitro pharmacological characterization, and pharmacodynamic studies in this species are warranted.
Abstract
Objective
To quantify the serum antibody responses to Pasteurella multocida A:3 outer membrane proteins (OMP) for cattle vaccinated with the homologous serogroup and to correlate those responses with the extent of experiment tally induced pneumonia.
Animals
29, 5- to 8-month-old beef-type calves.
Procedure
Calves were vaccinated SC or by aerosol exposure on davs 0 and 7 with live or killed P multocida or phosphate-buffered saline solution (control) and subsequently challenge exposed with virulent P multocida. Antibody responses to P multocida A:3 outer membranes were quantified, using an ELISA. Antibody responses to individual OMP were detected by immunoblot analysis (western blot) and were quantified by densitometry. Antibody responses were compared among groups of calves and for various times after vaccination. Regression analyses were used to determine whether significant correlations existed between lesion scores and antibody responses to either whole outer membranes or to individual OMP
Results
By ELISA, antibody responses to outer membranes for calves aerosol vaccinated with live P multocida were significantly (P < 0.05) greater than those for control calves or for killed P multocida vaccinates. There was a significant (P<0.05) correlation between lesion score and antibody responses to outer membranes. By western blotting and densitometry, antibodies to 11 prominent OMP (100, 97, 90, 85, 74, 53, 46 35, 32, 21, and 16 kd) were identified and quantified. In experiment 1, SC vaccination with live P multocida increased antibody binding to all protein bands except 85- 74-, and 35-kd bands. Aerosol vaccination with live P multocida stimulated increases in antibody binding to all bands except 100 and 16 kd. Antibody responses to the 97-, 90-, 74-, and 35- kd bands were significantly (P <0.05) greater for live aerosol vaccinates than for control calves. In experiment 2, antibody responses were not different between the killed P multocida vaccinates or control calves. Antibody responses for live P multocida aerosol vaccinates were significantly (P <0.05) greater than those for control calves for the 100-, 90-, 85-, 74-, 53-, 35-, and 16-kd bands. Regression analyses indicated significant correlations (P <0.05) between lesion score and antibody responses to the 100-, 90-, 53-, 46-, 35-, and 32-kd OMP.
Conclusions
Several OMP of P multocida type A:3 may be important for stimulating immunity to the organism in cattle. (Am J Vet Res 1996;57:1453-1457)
Abstract
Objectives
To compare the transmissibility by the brown dog tick, Rhipicephalus sanguineus, of a recent isolate of Ehrlichia canis (Ebony) with that of another isolate (Oklahoma) that had been passaged in cell culture, and to assess the genetic similarity of the 2 isolates as reflected in the nucleotide (NT) sequence of 16S rDNA.
Animals
13 healthy dogs of various ages and breeds.
Procedure
Larval and nymphal ticks were acquisition fed on acutely infected dogs, and, after molting, they were transmission fed as nymphs and adults, respectively, on Ehrlichia-naive dogs. All dogs were monitored daily by blood smear evaluation for evidence of parasitized leukocytes and by physical examination for clinical signs of ehrlichiosis. Serologic and hematologic values were measured weekly. Using a nested polymerase chain reaction, the 16S rDNA was amplified, and the NT sequence of the template DNA was determined.
Results
The Ebony isolate of E canis was successfully transmitted to dogs by nymphal and adult ticks. In contrast, no ticks that fed on dogs harboring the cell-cultured isolate (Oklahoma) transmitted it to dogs. On the basis of 16S rDNA sequence, the 2 isolates were 99.9% similar, with only 1 NT difference.
Conclusions
These results reconfirm the vector potential of R sanguineus for E canis. Passage of the Oklahoma isolate of E canis in cell culture apparently adversely affected its transmissibility by ticks, raising the possibility that cell-cultured isolates of this rickettsia may lose their affinity for ticks. Determination of 16S rDNA sequence suggests minor strain variation within the species E canis. (Am J Vet Res 1996;57:1594–1598)
Abstract
Objective—To identify the quantitative trait loci (QTL) that contribute to hip dysplasia in dogs.
Animals—192 Labrador Retrievers.
Procedures—Hip dysplasia was measured by use of the Norberg angle (NA), dorsolateral subluxation (DLS) score, and distraction index (DI). Genome-wide screening was conducted by use of 276 unique microsatellites. Linkage analysis was performed with a variance-based linear model. Logarithm of the odds (LOD) scores were reported when values were > 2.0.
Results—Canis familiaris autosomes (CFAs) 01, 02, 10, 20, 22, and 32 harbored significant QTL at LOD scores > 2.0. Among the 6 QTL, the QTL on CFA02 had not been reported to harbor QTL for hip dysplasia. The highest LOD score of 3.32 on CFA20 contributed to the second principal component of the DLS score and NA of the right hip joint. The QTL that was mapped on CFA01 (LOD score of 3.13 at 55 centimorgans) was located on the same chromosome reported to harbor a QTL for hip dysplasia in Portuguese Water Dogs and German Shepherd Dogs. In this study, CFAs 10, 20, 22, and 32 harbored QTL for hip dysplasia that have been identified in a Labrador Retriever–Greyhound pedigree and in German Shepherd Dogs.
Conclusions and Clinical Relevance—Multiple QTL were clearly involved with hip dysplasia. Identification of these QTL will enable fine-resolution mapping and subsequent assessment of candidate genes within the refined intervals to enable researchers to develop genetic screening tests and preventative and novel therapeutic regimens.
Abstract
OBJECTIVE
To identify an oral dose of grapiprant for red-tailed hawks (RTHAs; Buteo jamaicensis) that would achieve a plasma concentration > 164 ng/mL, which is considered therapeutic for dogs with osteoarthritis.
ANIMALS
6 healthy adult RTHAs.
PROCEDURES
A preliminary study, in which grapiprant (4 mg/kg [n = 2], 11 mg/kg [2], or 45 mg/kg [2]) was delivered into the crop of RTHAs from which food had been withheld for 24 hours, was performed to obtained pharmacokinetic data for use with modeling software to simulate results for grapiprant doses of 20, 25, 30, 35, and 40 mg/kg. Simulation results directed our selection of the grapiprant dose administered to the RTHAs in a single-dose study. Plasma grapiprant concentration, body weight, and gastrointestinal signs of RTHAs were monitored.
RESULTS
On the basis of results from the preliminary study and simulations, a grapiprant dose of 30 mg/kg was used in the single-dose study. The geometric mean maximum observed plasma concentration of grapiprant was 3,184 ng/mL, time to maximum plasma grapiprant concentration was 2.0 hours, and the harmonic mean terminal half-life was 17.1 hours. No substantial adverse effects were observed.
CONCLUSIONS AND CLINICAL RELEVANCE
Although the single dose of grapiprant (30 mg/kg) delivered into the crop achieved plasma concentrations > 164 ng/mL in the RTHAs, it was unknown whether this concentration would be therapeutic for birds. Further research that incorporates multidose assessments, safety monitoring, and pharmacodynamic data collection is warranted on the use of grapiprant in RTHAs from which food was withheld versus not withheld.
SUMMARY
Streak retinoscopy was performed by 5 ophthalmologists on 256 eyes (191 dogs) to determine their postoperative refractive state after cataract extraction. Aphakic and pseudophakic eyes that had been implanted with 1 of 5 intraocular lenses (iol) with dioptric powers ranging from + 14.5 to + 38 diopters (D) were studied. By use of ANOVA, breed and body type of dog and individual performing refraction were found to have no detectable effect on final refractive state. Mean refractive state of aphakic eyes was +14.4 ± 2.10 D. Mean refractive state for different iol powers was as follows: + 14.5 D iol = + 11.54 ± 1.18 D (n = 13); +30 D iol = + 5.15 ± 1.18 D (n = 105); + 34.0 D iol = +3.5 D (n = 1); +36 D iol = +2.34 ± 0.73 D 9 (n = 61); and +38 D iol = + 1.41 ± 0.56 D (n = 28). Residual hyperopia ranged from +0.5 D to +2.5 D with +38 D iol, and no eyes were myopic (overcorrected) by use of any of the iol studied. Linear regression analysis of refractive state on iol power for all dogs predicted that dioptric strength of +41.53 D was necessary to best approximate emmetropia for the population as a whole. Body type of the dog had only slight effect (< 1.0 D) on predicted optimal iol power. Further linear regression analysis of the 7 breeds studied predicted variations from +39.62 to +43.14 D in iol powers necessary to approximate emmetropia. Results of the study support the routine use of canine iol with dioptric strength of approximately + 41.5 D in circumstances in which preoperative biometry and keratometry are not practical. The findings further suggest that, for the specific population of dogs studied, most of the dogs could be corrected to near emmetropia by use of a small range of iol dioptric strengths, irrespective of body type or breed.
Abstract
OBJECTIVE To determine the clinical features, treatment, and outcomes of treatment for oral and cutaneous squamous cell carcinoma (SCC) in avian species.
DESIGN Retrospective case series with nested cohort study.
ANIMALS 87 client-owned birds of various species with histologically confirmed SCC of the skin or oral cavity.
PROCEDURES Clinicians entered case information through an online survey tool. Data were collected regarding patient signalment, concurrent conditions, treatments, adverse effects, and clinical outcomes. Relationships were examined between complete excision and partial or complete response. Survival analysis was performed to compare outcomes among groupings of therapeutic approaches.
RESULTS Only 7 of 64 (11%) birds for which full outcome data were available had complete remission of SCC; 53 (83%) had progressive disease, were euthanized, or died of the disease. The unadjusted OR for partial or complete response following complete tumor excision (vs other treatment approaches) was 6.9 (95% confidence interval [CI], 1.8 to 25.8). Risk of death was 62% lower (hazard ratio, 0.38; 95% CI, 0.19 to 0.77) for birds that underwent complete excision versus conservative treatment. Median survival time from initial evaluation for birds receiving complete excision was 628 days (95% CI, 210 to 1,008 days), compared with 171 days (95% CI, 89 to 286 days) for birds receiving monitoring with or without conservative treatment. Birds receiving any other additional treatment had a median survival time of 357 days (95% CI, 143 to 562 days).
CONCLUSIONS AND CLINICAL RELEVANCE For birds with SCC, complete excision was the only treatment approach significantly associated with complete or partial response and increased survival time.
Abstract
Objective—To determine whether treatment with selamectin would reduce clinical signs of flea allergy dermatitis (FAD) in dogs and cats housed in flea-infested environments.
Design—Randomized controlled trial.
Animals—22 dogs and 17 cats confirmed to have FAD.
Procedure—Animals were housed in carpeted pens capable of supporting the flea life cycle and infested with 100 fleas (Ctenocephalides felis) on days –13 and –2 and on alternate weeks with 10 to 20 fleas. On day 0, 11 dogs and 8 cats were treated with selamectin (6 mg/kg [2.7 mg/lb]). Dogs were retreated on day 30; cats were retreated on days 30 and 60. All animals were examined periodically for clinical signs of FAD. Flea counts were conducted at weekly intervals.
Results—Throughout the study, geometric mean flea counts exceeded 100 for control animals and were ≤ 11 for selamectin-treated animals. Selamectin-treated cats had significant improvements in the severity of miliary lesions and scaling or crusting on days 42 and 84, compared with conditions on day –8, and in severity of excoriation on day 42. In contrast, control cats did not have any significant improvements in any of the clinical signs of FAD. Selamectin-treated dogs had significant improvements in all clinical signs on days 28 and 61, but in control dogs, severity of clinical signs of FAD was not significantly different from baseline severity at any time.
Conclusions and Clinical Relevance—Results suggest that topical administration of selamectin, even without the use of supplementary environmental control measures and with minimal therapeutic intervention, can reduce the severity of clinical signs of FAD in dogs and cats. (J Am Vet Med Assoc 2003;223:639–644)
Summary
To investigate the interaction between Mycoplasma hyopneumoniae and Pasteurella multocida infection, 32 pigs were randomly assigned by litter, sex, and weight to 4 treatment groups. Group-1 pigs were inoculated with M hyopneumoniae and allowed to recover from M hyopneumoniae infection. Group-2 pigs were vaccinated against M hyopneumoniae and then inoculated with M hyopneumoniae. Group-3 pigs were inoculated with M hyopneumoniae and developed clinical signs of mycoplasmosis. Group-4 pigs had never been exposed to M hyopneumoniae. All pigs were initially seronegative for M hyopneumoniae. All pigs were subsequently inoculated with P multocida and euthanatized 2 weeks later. Pasteurella multocida was isolated only from the lungs of group-3 pigs, and these pigs had a significantly higher median percentage of lung surface area affected by pneumonia than did pigs in the other groups. For group-3 pigs, percentage of lung surface area affected by pneumonia was positively correlated with the number of P multocida colonies isolated. We concluded that P multocida is not a primary respiratory pathogen in pigs, but that M hyopneumoniae infection can render the lungs susceptible to P multocida colonization and infection. Pigs recovered from or vaccinated against infection with M hyopneumoniae were resistant to P multocida infection.
Abstract
Objective—To determine opinions of faculty members with clinical appointments, clinical veterinarians, residents, and interns at a US veterinary teaching hospital regarding antimicrobial use and antimicrobial-resistant infections.
Design—Cross-sectional survey.
Sample—71 veterinarians.
Procedures—An online questionnaire was sent to all veterinarians with clinical service responsibilities at the North Carolina State University veterinary teaching hospital (n = 167). The survey included 23 questions regarding demographic information, educational experiences, current prescribing practices, and personal opinions related to antimicrobial selection, antimicrobial use, restrictions on antimicrobial use, and antimicrobial resistance.
Results—Of the 167 veterinarians eligible to participate, 71 (43%) responded. When respondents were asked to rate their level of concern (very concerned = 1; not concerned = 5) about antimicrobial-resistant infections, most (41/70 [59%]) assigned a score of 1, with mean score for all respondents being 1.5. Most survey participants rated their immediate colleagues (mean score, 1.9) as more concerned than other veterinary medical professionals (mean score, 2.3) and their clients (mean score, 3.4). Fifty-nine of 67 (88%) respondents felt that antimicrobials were overprescribed at the hospital, and 32 of 69 (46%) respondents felt uncomfortable prescribing at least one class of antimicrobials (eg, carbapenems or glycopeptides) because of public health concerns.
Conclusions and Clinical Relevance—Findings indicated that veterinarians at this teaching hospital were concerned about antimicrobial resistance, thought antimicrobials were overprescribed, and supported restricting use of certain antimicrobial classes in companion animals. Findings may be useful in educating future veterinarians and altering prescribing habits and antimicrobial distribution systems in veterinary hospitals.