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Abstract

Objective—To determine effects of various diets on the pharmacokinetics of phenobarbital and the interactive effects of changes in body composition and metabolic rate.

Design—Prospective study.

Animals—27 healthy sexually intact adult female Beagles.

Procedure—Pharmacokinetic studies of phenobarbital were performed before and 2 months after dogs were fed 1 of 3 diets (group 1, maintenance diet; group 2, protein-restricted diet; group 3, fat- and protein-restricted diet) and treated with phenobarbital (approx 3 mg/kg [1.4 mg/lb] of body weight, PO, q 12 h). Pharmacokinetic studies involved administering phenobarbital (15 mg/kg [6.8 mg/lb], IV) and collecting blood samples at specific intervals for 240 hours. Effects of diet and time were determined by repeated-measures ANOVA.

Results—Volume of distribution, mean residence time, and half-life (t1/2) of phenobarbital significantly decreased, whereas clearance rate and elimination rate significantly increased with time in all groups. Dietary protein or fat restriction induced significantly greater changes: t1/2 (hours) was lower in groups 2 (mean ± SD; 25.9 ± 6.10 hours) and 3 (24.0 ± 4.70) than in group 1 (32.9 ± 5.20). Phenobarbital clearance rate (ml/kg/min) was significantly higher in group 3 (0.22 ± 0.05 ml/kg/min) than in groups 1 (0.17 ± 0.03) or 2 (0.18 ± 0.03). Induction of serum alkaline phosphatase activity (U/L) was greater in groups 2 (192.4 ± 47.5 U/L) and 3 (202.0 ± 98.2) than in group 1 (125.0 ± 47.5).

Conclusions and Clinical Relevance—Clinically important differences between diet groups were observed regarding pharmacokinetics of phenobarbital, changes in CBC and serum biochemical variables, and body composition. Drug dosage must be reevaluated if a dog's diet, body weight, or body composition changes during treatment. Changes in blood variables that may indicate liver toxicosis caused by phenobarbital may be amplified by diet-drug interactions. (J Am Vet Med Assoc 2000;217:847–852)

Full access
in Journal of the American Veterinary Medical Association

Abstract

Objective

To test the association between exposure to bovine coronavirus (BCV) and outbreaks of winter dysentery (WD) in dairy herds and to examine other risk factors for outbreaks of WD in dairy herds.

Animals

12 dairy herds in Ohio affected with WD (case herds). For each case herd, 2 unaffected herds from the same area were concurrently used as control herds.

Procedure

A case-control study was conducted, using herds as the unit of investigation. Multivariate logistic regression modeling was used to identify risk factors for contracting disease.

Results

4 factors appeared to increase a herd's risk for WD: increase in herd prevalence of adult cows that had a fourfold or more increase in BCV serum IgG antibody titer; increase in herd prevalence of adult cows that had a fourfold or more increase in bovine viral diarrhea virus (BVDV) titer; housing cattle in tie-stall or stanchion barns rather than free-stall facilities; and use of equipment to handle manure and subsequently handle feed. The adjusted population-attributable risk for these variables was 71, 43, 53, and 31%, respectively, and 99% overall, indicating that these variables had considerable impact on WD outbreaks for the study population.

Conclusions and Clinical Relevance

In dairies in Ohio, recent herd exposure to BCV appeared to increase the risk for WD outbreaks. Some WD outbreaks might have been associated with acute BVDV infection. Certain housing and management practices may have increased the risk of an outbreak of WD. (Am J Vet Res 1998;59:994–1001)

Free access
in American Journal of Veterinary Research

Abstract

Objective

To identify exposures to etiologic agents and to identify characteristics that could explain risk of disease for adult cattle in herds affected by winter dysentery (WD).

Animals

229 lactating and nonlactating adult cattle (125 case and 104 control cattle) selected from 12 dairy herds.

Procedure

A case-control study, using multivariate conditional logistic regression and controlling for herd effects, was used to develop a model for risk factors associated with disease for each cow.

Results

Likelihood of developing disease increased as the ELISA value for bovine coronavirus (BCV) antigen detectable in feces increased (odds ratio [OR] = 2.94 for each 0.100 increase in BCV antigen ELISA value). Pregnant cattle were less likely to develop WD, compared with nonpregnant herdmates. Cows with high acute BCV antibody titers that seroresponded had greater odds of developing disease, compared with seroresponding cows with low acute titers. However, among those cows that did not serorespond, high acute antibody titers were associated with lower odds of developing the disease.

Conclusion

In herds affected by WD, ill cows were more likely to shed detectable amounts of BCV antigen in their feces, and pregnancy appeared to protect cattle from the disease. The measured interaction between BCV seroresponse and acute BCV antibody titer may be evidence of an immunopathologic condition, but could also have been attributable to dynamics of the ELISA or study design.

Clinical Relevance

Factors that explained a cow's risk for illness within WD-affected herds may have been surrogate measures for that cow's nonspecific and BCV-specific immune profile. (Am J Vet Res 1998;59:986–993)

Free access
in American Journal of Veterinary Research

SUMMARY

Using an applanation tonometer, 5 replicate intraocular pressure (iop) measurements were obtained from each eye of 12 young, clinically normal, American alligators. Alligator length ranged from 46 to 117 cm, measured from snout to tail tip. All iop were recorded by a single observer at an ambient temperature of approximately 25 C, and ranged from 5 to 35 mm of Hg. Observer reliability was excellent (intraclass r = 0.93), and iop did not change over the ordered sequence of 5 replicate measurements/eye. Replicate iop measurements were, therefore, averaged in each eye for comparison between eyes of the same alligator. Left and right eye iop were highly correlated within individual alligators (r = 0.92), whereas the mean within-animal difference between left and right eye iop was not statistically significant (95% confidence interval [ci] for the left eye-right eye mean difference, −1.9 to 1.5 mm of Hg). Mean iop determined for 5 confirmed females and 3 confirmed males did not differ significantly between the sexes (95% ci for the male-female difference in means, −2.1 to 3.7 mm of Hg). Mean ± sem iop of 23.7 + 2.1 mm of Hg determined for 4 alligators < 50 cm long was significantly (P = 0.009) greater than mean iop of 11.6 + 0.5 mm of Hg determined for 8 alligators > 50 cm long (95% ci for the difference in means, 8.5 to 15.7 mm of Hg). In young alligators, the relation between body length and iop appears to be nonlinear, possibly with a negative exponent.

Free access
in American Journal of Veterinary Research

Abstract

Objective

To evaluate efficacy of florfenicol treatment for bovine mastitis caused by Streptococcus agalactiae, Staphylococcus aureus, nonagalactiae streptococci, coagulase-negative staphylococci, Escherichia coli, Klebsiella sp, and others.

Design

Double blind study with cases randomly assigned to 1 of 2 treatment groups.

Sample Population

861 cows/10 commercial dairy farms.

Procedures

Experimental (750 mg of florfenicol) or control (200 mg of cloxacillin) treatment was administered by intramammary infusion every 12 hours for 3 treatments to all cases. Treatments were randomly assigned, identified only by numerical labels. To retain blinding, the longer withdrawal time was adhered to for all cases. Cases remained in the study only if there was no other treatment. Quarter samples were recultured 14, 21, and 28 days later. If all samples after day 1 were culture negative, the case was defined as cured. If only 1 of the follow-up results was positive, the case was considered cured if the day-28 somatic cell count was < 300,000/ml. Failure of treatment was defined as 2 or more culture-positive follow-up samples.

Results

Florfenicol and cloxacillin did not differ significantly in efficacy versus clinical (n = 85) or subclinical (n = 71) bovine mastitis, or for any etiologic agent (χ2). Overall cure rates for mastitis were: Str agalactiae, 5 of 8 (63%); Sta aureus, 5 of 54 (9%); Streptococcus sp, 16 of 35 (46%); Staphylococcus sp, 7 of 33 (21 %); E coli, 5 of 11 (46%); Klebsiella sp, 3 of 6 (50%); others, 1 of 9 (11%); and all cases, 42 of 156 (27%).

Conclusions

Florfenicol did not offer any advantage over cloxacillin in efficacy against bovine mastitis. Overall cure rates were low. As with most mastitis treatment regimens, poor efficacy may be partly attributable to the short duration of treatment. (Am J Vet Res 1996;57:526–528)

Free access
in American Journal of Veterinary Research

Abstract

OBJECTIVE To determine the effect of age on the pharmacokinetics and pharmacodynamics of flunixin meglumine following IV and transdermal administration to calves.

ANIMALS 8 healthy weaned Holstein bull calves.

PROCEDURES At 2 months of age, all calves received an injectable solution of flunixin (2.2 mg/kg, IV); then, after a 10-day washout period, calves received a topical formulation of flunixin (3.33 mg/kg, transdermally). Blood samples were collected at predetermined times before and for 48 and 72 hours, respectively, after IV and transdermal administration. At 8 months of age, the experimental protocol was repeated except calves received flunixin by the transdermal route first. Plasma flunixin concentrations were determined by liquid chromatography-tandem mass spectroscopy. For each administration route, pharmacokinetic parameters were determined by noncompartmental methods and compared between the 2 ages. Plasma prostaglandin (PG) E2 concentration was determined with an ELISA. The effect of age on the percentage change in PGE2 concentration was assessed with repeated-measures analysis. The half maximal inhibitory concentration of flunixin on PGE2 concentration was determined by nonlinear regression.

RESULTS Following IV administration, the mean half-life, area under the plasma concentration-time curve, and residence time were lower and the mean clearance was higher for calves at 8 months of age than at 2 months of age. Following transdermal administration, the mean maximum plasma drug concentration was lower and the mean absorption time and residence time were higher for calves at 8 months of age than at 2 months of age. The half maximal inhibitory concentration of flunixin on PGE2 concentration at 8 months of age was significantly higher than at 2 months of age. Age was not associated with the percentage change in PGE2 concentration following IV or transdermal flunixin administration.

CONCLUSIONS AND CLINICAL RELEVANCE In calves, the clearance of flunixin at 2 months of age was slower than that at 8 months of age following IV administration. Flunixin administration to calves may require age-related adjustments to the dose and dosing interval and an extended withdrawal interval.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To provide an updated evaluation of the efficacy and safety of sometribove zinc suspension (rbST-Zn), a form of recombinant bovine somatotropin, in lactating dairy cows.

Design—Meta-analysis.

Sample—26 studies published in peer-reviewed journals or reviewed by a regulatory agency.

Procedures—To be included, a study had to involve the use of the rbST-Zn formulation available to US producers in accordance with the label instructions for treatment initiation (57 to 70 days postpartum), dose (500 mg, q 14 d), and route (SC).

Results—For cows treated with rbST-Zn, mean milk, 3.5% fat-corrected milk, fat, and protein yields were increased by 4.00, 4.04, 0.144, and 0.137 kg/d (8.8, 8.89, 0.32, and 0.30 lb/d), respectively; however, the concentration of milk components did not change. Pregnancy proportion for the first 2 breeding cycles was increased by 5.4%, and pregnancy proportion for the duration of the trial was reduced by 5.5% for rbST-Zn–treated cows, compared with proportions for untreated cows. Mean body condition score (1 to 5 scale) was reduced by 0.06 points during the period of rbST-Zn use for treated cows. Administration of rbST-Zn had no effect on milk somatic cell count, the number of days to pregnancy, or inseminations per pregnancy; rates of fetal loss, twins, cystic ovaries, clinical lameness, lameness lesions, or traumatic lesions of the integumentary system; and odds of clinical mastitis or culling.

Conclusions and Clinical Relevance—Results indicated that rbST-Zn administration to dairy cows effectively increases milk production with no adverse effects on cow health and well-being.

Full access
in Journal of the American Veterinary Medical Association

Abstract

Objective—To evaluate the effects of diet restriction on development of radiographic evidence of hip joint osteoarthritis in dogs.

Design—Longitudinal cohort study.

Animals—48 Labrador Retrievers from 7 litters.

Procedures—Forty-eight 6-week-old puppies from 7 litters were paired with littermates by sex and weight, and each pairmate was randomly assigned to 1 of 2 groups of 24 dogs each. Starting at 8 weeks of age, 1 group was fed ad libitum (control fed) and the other was fed 25% less (restricted fed) of the same diet for life on a pairwise basis. The dogs' hip joints were radiographed in the standard ventrodorsal hip-extended view at multiple intervals prior to 1 year of age and at annual intervals thereafter on the basis of birth anniversary. A board-certified radiologist unaware of group assignment scored the radiographs for evidence of osteoarthritis.

Results—Prevalence of radiographic evidence of hip joint osteoarthritis in all dogs increased linearly throughout the study, from an overall prevalence of 15% at 2 years to 67% by 14 years. Restricted-fed dogs had lower prevalence and later onset of hip joint osteoarthritis. Median age at first identification of radiographic evidence of hip joint osteoarthritis was significantly lower in the control-fed group (6 years), compared with the restricted-fed group (12 years).

Conclusions and Clinical Relevance—Restricted feeding delayed or prevented development of radiographic signs of hip joint osteoarthritis in this cohort of Labrador Retrievers. Lifetime maintenance of 25% diet restriction delayed onset and reduced severity of hip joint osteoarthritis, thus favorably affecting both duration and quality of life. In addition, the data indicated that development of hip joint osteoarthritis was not bimodal in these dogs but occurred as a continuum throughout life.

Full access
in Journal of the American Veterinary Medical Association

Summary

Cardiovascular and respiratory changes that accompany markedly long periods (12 hours) of halothane anesthesia were characterized. Eight spontaneously breathing horses were studied while they were positioned in left lateral recumbency and anesthetized only with halothane in oxygen maintained at a constant end-tidal concentration of 1.06% (equivalent to 1.2 times the minimal alveolar concentration for horses). Results of circulatory and respiratory measurements during the first 5 hours of constant conditions were similar to those previously reported from this laboratory (ie, a time-related significant increase in systemic arterial blood pressure, cardiac output, stroke volume, left ventricular work, pcv, plasma total solids concentration, and little change in respiratory system function). Beyond 5 hours of anesthesia, arterial blood pressure did not further increase, but remained above baseline. Cardiac output continued to increase, because heart rate significantly (P < 0.05) increased. Peak inspiratory gas flow increased significantly (P < 0.05) in later stages of anesthesia. There was a significant decrease in inspiratory time beginning at 4 hours. Although PaO2 and PaCO2 did not significantly change during the 12 hours of study, P v ̄ O 2 increased significantly (P < 0.05) and progressively with time, beginning 6 hours after the beginning of constant conditions. Metabolic acidosis increased with time (significantly [P < 0.05] starting at 9 hours), despite supplemental iv administered NaHCO3, Plasma concentrations of eicosanoids: 6-ketoprostaglandin F (pgf a stable metabolite of pgi 1), pgf , pge, and thromboxane (TxB2, a stable metabolite of TxA2) were measured in 5 of the 8 horses before and during anesthesia. Significant changes from preanesthetic values were not detected. Dynamic thoracic wall and lung compliances decreased with time.

Free access
in American Journal of Veterinary Research

Abstract

OBJECTIVE To describe use of whole-genome sequencing (WGS) and evaluate the apparent sensitivity and specificity of antemortem tuberculosis tests during investigation of an unusual outbreak of Mycobacterium bovis infection in a Michigan dairy herd.

DESIGN Bovine tuberculosis (bTB) outbreak investigation.

ANIMALS Cattle, cats, dog, and wildlife.

PROCEDURES All cattle in the index dairy herd were screened for bTB with the caudal fold test (CFT), and cattle ≥ 6 months old were also screened with a γ-interferon (γIFN) assay. The index herd was depopulated along with all barn cats and a dog that were fed unpasteurized milk from the herd. Select isolates from M bovis–infected animals from the index herd and other bTB-affected herds underwent WGS. Wildlife around all affected premises was examined for bTB.

RESULTS No evidence of bTB was found in any wildlife examined. Within the index herd, 53 of 451 (11.8%) cattle and 12 of 21 (57%) cats were confirmed to be infected with M bovis. Prevalence of M bovis–infected cattle was greatest among 4- to 7-month-old calves (16/49 [33%]) followed by adult cows (36/203 [18%]). The apparent sensitivity and specificity were 86.8% and 92.7% for the CFT and 80.4% and 96.5% for the γIFN assay when results for those tests were interpreted separately and 96.1% and 91.7% when results were interpreted in parallel. Results of WGS revealed that M bovis–infected barn cats and cattle from the index herd and 6 beef operations were infected with the same strain of M bovis. Of the 6 bTB-affected beef operations identified during the investigation, 3 were linked to the index herd only by WGS results; there was no record of movement of livestock or waste milk from the index herd to those operations.

CONCLUSIONS AND CLINICAL RELEVANCE Whole-genome sequencing enhanced the epidemiological investigation and should be used in all disease investigations. Performing the CFT and γIFN assay in parallel improved the antemortem ability to detect M bovis–infected animals. Contact with M bovis–infected cattle and contaminated milk were major risk factors for transmission of bTB within and between herds of this outbreak.

Full access
in Journal of the American Veterinary Medical Association