Temperatures of storage areas in large animal veterinary practice vehicles in the summer and comparison with drug manufacturers’ storage recommendations

Background: Large animal veterinarians carry drugs in their practice vehicles in storage areas that are not typically refrigerated. The most common upper limits of manufacturers’ storage temperatures for United States (U.S.)-approved non-refrigerated drugs are 25 or 30 °C. Because ambient temperatures in many locations in the U.S. exceed these temperatures during the summer, we measured storage area temperatures over 4 months in the summer of 2013 to evaluate the extent to which labeled storage temperatures are exceeded. Methods: A convenience sample of 12 vehicles from 5 central Texas practices and 12 vehicles from 4 south central Nebraska practices was used. Temperatures were recorded in one drug storage compartment in each vehicle from May 15 – September 16, 2013, at 15-minute intervals using a self-contained, battery operated temperature recording device. Results: The highest temperatures recorded in a storage unit were 54.4 and 47.7 °C in Texas and Nebraska, respectively. The mean temperature recorded across all 24 storage units was 29.1 °C, with a mean of 26.9 °C in Nebraska and 31.4 °C in Texas. In Nebraska, at least one temperature over 25 °C was recorded on a mean of 111/124 days and a mean of 63 % of total logger readings. In Texas, temperatures over 25 °C were recorded on a mean of 123/124 days and a mean of 95 % of total logger readings. Conclusions: Temperatures in storage units in participating veterinary practice vehicles exceeded labeled drug storage temperatures a significant portion of the summer of 2013. More research is needed to determine whether these excursions above the manufacturers’ recommended storage temperatures alter efficacy of stored drugs

An experimental model for calcium carbonate urolithiasis in goats

This article is also available at the journal website: https://onlinelibrary.wiley.com/doi/full/10.1111/jvim.15061Background: Calcium carbonate is a common urolith type in small ruminants with no high-yield experimental model to evaluate animal susceptibility or preventative measure response. Hypothesis: That novel plastic winged implants would allow accumulation and quantification of calcium carbonate calculus formation in goats on a high-calcium diet and identify individual variation between goats in the mass of calculi produced. Animals: Eight nonpregnant 3- and 4-year-old Boer-cross does, weighing 22.3–39.5 kg, determined to be healthy based on physical examination, were used in these experiments. Methods: Prospective cohort study for in vivo experimental model development. Implants were placed into the urinary bladder lumen in 8 goats over 2 evaluation periods. The alfalfa-based ration had a total ration Ca : P of 3.29 and 3.84 : 1, respectively. Urine was collected at 0, 28, 56, and 84 days in the 1st experiment; blood and urine at those timepoints in the 2nd experiment. For each evaluation period, the implants were removed 84 days after implantation and weighed. Accumulated calculi mass was calculated and compared between goats and was analyzed for composition. Results: Implant retention was 100% and 86% in the 2 studies. All goats with retained implants accumulated calcium carbonate at a mean implant gain per day across studies ranging from 0.44 to 57.45 mg. Two goats accumulated (0.44–7.65 mg/day and 33.64 & 57.45 mg/day) significantly more urolith material than the cohort across both studies (P5.047). No routine analytes on blood or urine were found to be explanatory for the difference observed. Conclusions and Clinical Importance: These findings form a basis for implant and diet selection for use in future studies of urolithiasis development and for studies regarding individual susceptibility to urolithiasis. KEYWORDS 3D printing, calculogenesis, urinary calculi, urolithFunding information: Department of Large Animal Clinical Sciences, Texas A&M University College of Veterinary Medicin

North American Hard Yellow Liver Disease: An Old Problem Readdressed

Hard yellow liver disease or fatty cirrhosis periodically affects cattle, sheep, goats, pronghorn antelope (Antilocapra americana) and whitetail deer (Odocoileus virginianus texanus) within several Texas counties in the United States. Clinically it presents as chronic liver disease with progressive hepatic necrosis and fibrosis, icterus and liver failure. The damaged livers are yellow and many have multiple firm, often gritty foci that are scattered throughout all lobes. Early investigations included feeding studies using potential toxic plants, climate and forage studies, infectious disease surveys and various mycotoxin studies and analyses. None have definitively reproduced the disease or identified the inciting cause. However, the problem continues and recent outbreaks have allowed the collection of additional frozen tissues, and numerous paraffin tissue blocks and slides for additional studies. The objectives for this work are to evaluate and compare the microscopic changes, special histochemical studies, microbial and fungal surveys and chemical assays for dehyro-pyrrolizidine alkaloid (DHPA) metabolites of these additional cases with historical reports. These bovine livers had a spectrum of lesions including lipid degeneration and necrosis, eosinophilic granulomatous hepatitis, focal follicular lymphoid proliferation and chronic fibrosing hepatitis with dystrophic mineralization. No pyrrolizidine alkaloid metabolites were detected in any of the livers and select special stains did not reveal any fungal, bacterial or parasitic etiologies. The lack of findings and mixed histologic presentation suggest that this syndrome is a collection of chronic diseases probably of various etiologies. Earlier animal surveillance work is needed in endemic areas to better understand the etiology and pathogenesis of this syndrome

Temperatures of storage areas in large animal veterinary practice vehicles in the summer and comparison with drug manufacturers’ storage recommendations

Background: Large animal veterinarians carry drugs in their practice vehicles in storage areas that are not typically refrigerated. The most common upper limits of manufacturers’ storage temperatures for United States (U.S.)-approved non-refrigerated drugs are 25 or 30 °C. Because ambient temperatures in many locations in the U.S. exceed these temperatures during the summer, we measured storage area temperatures over 4 months in the summer of 2013 to evaluate the extent to which labeled storage temperatures are exceeded. Methods: A convenience sample of 12 vehicles from 5 central Texas practices and 12 vehicles from 4 south central Nebraska practices was used. Temperatures were recorded in one drug storage compartment in each vehicle from May 15 – September 16, 2013, at 15-minute intervals using a self-contained, battery operated temperature recording device. Results: The highest temperatures recorded in a storage unit were 54.4 and 47.7 °C in Texas and Nebraska, respectively. The mean temperature recorded across all 24 storage units was 29.1 °C, with a mean of 26.9 °C in Nebraska and 31.4 °C in Texas. In Nebraska, at least one temperature over 25 °C was recorded on a mean of 111/124 days and a mean of 63 % of total logger readings. In Texas, temperatures over 25 °C were recorded on a mean of 123/124 days and a mean of 95 % of total logger readings. Conclusions: Temperatures in storage units in participating veterinary practice vehicles exceeded labeled drug storage temperatures a significant portion of the summer of 2013. More research is needed to determine whether these excursions above the manufacturers’ recommended storage temperatures alter efficacy of stored drugs

Metronidazole for the treatment of Tritrichomonas foetus in bulls

Abstract Background: Tritrichomonas foetus is a sexually transmitted protozoon that causes reproductive failure, among cattle, so disruptive that many western US states have initiated control programs. Current control programs are based on the testing and exclusion of individual bulls. Unfortunately, these programs are utilizing screening tests that are lacking in sensitivity. Blanket treatment of all the exposed bulls and adequate sexual rest for the exposed cows could provide a more viable disease control option. The objectives of this study were twofold. The first objective was to demonstrate effectiveness for metronidazole treatment of a bull under ideal conditions and with an optimized treatment regime. This type of study with a single subject is often referred to as an n-of-1 or single subject clinical trial. The second objective of the current study was to review the scientific basis for the banning of metronidazole for use in Food Animals by the Animal Medicinal Drug Use Clarification Act of 1994 (AMDUCA). Results: Results from an antimicrobial assay indicated that metronidazole at a concentration of 0.5 μg/mL successfully eliminated in vitro protozoal growth of bovine Tritrichomonas foetus. The estimated effective intravenous dose was two treatments with 60 mg/kg metronidazole, 24 h apart. A bull that had tested positive for Tritrichomonas foetus culture at weekly intervals for 5 weeks prior to treatment was negative for Tritrichomonas foetus culture at weekly intervals for five consecutive weeks following this treatment regimen. An objective evaluation of the published evidence on the potential public health significance of using metronidazole to treat Tritrichomonas foetus in bulls provides encouragement for veterinarians and regulators to consider approaches that might lead to permitting the legal use of metronidazole in bulls. Conclusion: The study demonstrated successful inhibition of Tritrichomonas foetus both in vitro and in vivo with metronidazole. The current status of metronidazole is that the Animal Medicinal Drug Use Clarification Act of 1994 prohibits its extra-label use in food-producing animals. Veterinarians and regulators should consider approaches that might lead to permitting the legal use of metronidazole in bulls. Keywords: Tritrichomonas feotus, metronidazole, cattleTexas A&M University Department of Large Animal Clinical Sciences

Synovial pharmacokinetics of tulathromycin, gamithromycin and florfenicol after a single subcutaneous dose in cattle

Background: Deep digital septic conditions represent some of the most refractory causes of severe lameness in cattle. The objective of this study was to determine the distribution of tulathromycin, gamithromycin and florfenicol into the synovial fluid of the metatarsophalangeal (MTP) joint of cattle after single subcutaneous administration of drug to evaluate the potential usefulness of these single-dose, long-acting antimicrobials for treating bacterial infections of the joints in cattle. Results: Twelve cross-bred beef cows were randomly assigned to one of the drugs. Following subcutaneous administration, arthrocentesis of the left metatarsophalangeal joint was performed at various time points up to 240 hours post-injection, and samples were analyzed for drug concentration. In synovial fluid, florfenicol pharmacokinetic parameters estimates were: mean Tmax 7 +/− 2 hours, mean t½ 64.9 +/− 20.1 hours and mean AUC0-inf 154.0 +/− 26.2 ug*h/mL. Gamithromycin synovial fluid pharmacokinetic parameters estimates were: mean Tmax 8 hours, mean t½ 77.9 +/− 30.0 hours, and AUC0-inf 6.5 +/− 2.9 ug*h/mL. Tulathromycin pharmacokinetic parameters estimates in synovial fluid were: Tmax 19 +/− 10 hours, t½ 109 +/− 53.9 hours, and AUC0-inf 57.6 +/− 28.2 ug h/mL. Conclusions: In conclusion, synovial fluid concentrations of all three antimicrobials were higher for a longer duration than that of previously reported plasma values. Although clinical data are needed to confirm microbiological efficacy, florfenicol achieved a synovial fluid concentration greater than the MIC90 for F. necrophorum for at least 6 days.The open access fee for this work was funded through the Texas A&M University Open Access to Knowledge (OAK) Fund