Murray P. Brown

Study of intragastric administration of doxycycline: pharmacokinetics including body fluid, endometrial and minimum inhibitory concentrations

The objectives of this study were to determine the pharmacokinetics and tissue concentrations of doxycycline after repeated intragastric administration, and to determine the minimum inhibitory concentrations (MIC) for equine pathogenic bacteria. In experiment 1, 2 mares received a single intragastric dose of doxycycline hyclate (3 mg/kg bwt). Mean peak serum concentration was 0.22 microg/ml 1 h postadministration. In experiment 2, 5 doses of doxycycline hyclate (10 mg/kg bwt), dissolved in water, were administered to each of 6 mares via nasogastric tube at 12 h intervals. The mean +/- s.e. peak serum doxycycline concentration was 0.32+/-0.16 microg/ml 1 h after the first dose and 0.42+/-0.05 microg/ml 2 h after the fifth dose. The mean trough serum concentrations were > 0.16 microg/ml. Highest mean synovial concentration was 0.46+/-0.13 microg/ml and highest mean peritoneal concentration was 0.43+/-0.07 microg/ml, both 2 h after the fifth dose. Highest urine concentration was mean +/- s.e. 145+/-25.4 microg/ml 2 h after the last dose. Highest endometrial concentration was mean +/- s.e. 1.30+/-0.36 microg/ml 3 h after the fifth dose. Doxycycline was not detected in any of the CSF samples. Mean +/- s.e. Vd(area) was 25.3+/-5.0 l/kg and mean t1/2 was 8.7+/-1.6 h. In experiment 3, minimum inhibitory concentrations of doxycycline were determined for 168 equine bacterial culture specimens. The MIC90 was < or = 1.0 microg/ml for Streptococcus zooepidemicus and 0.25 microg/ml for Staphylococcus aureus. Based on drug concentrations achieved in the serum, synovial and peritoneal fluids and endometrial tissues and MIC values determined in the present study, doxycycline at a dose of 10 mg/kg bwt per os every 12 h may be appropriate for the treatment of infections caused by susceptible (MIC < 0.25 microg/ml) gram-positive organisms in horses.

Comparison of two indirect techniques for local delivery of a high dose of an antimicrobial in the distal portion of forelimbs of horses.

OBJECTIVE To compare isolated limb retrograde venous injection (ILRVI) and isolated limb infusion (ILI) for delivery of amikacin to the synovial fluid of the distal interphalangeal and metacarpophalangeal joints and to evaluate the efficacy of use of an Esmarch tourniquet in standing horses. ANIMALS 6 healthy adult horses. PROCEDURES Horses were randomly assigned in a crossover design. In ILRVI, the injection consisted of 1 g of amikacin diluted to a total volume of 60 mL administered during a 3-minute period. In ILI, the infusion consisted of 1 g of amikacin diluted to 40 mL administered during a 3-minute period followed by administration of boluses of diluent (82 mL total) to maintain vascular pressure. During ILI, the infusate and blood were circulated from the venous to the arterial circulation in 5-mL aliquots. Synovial fluid and serum samples were obtained to determine maximum amikacin concentrations and tourniquet leakage, respectively. RESULTS Both techniques yielded synovial concentrations of amikacin > 10 times the minimum inhibitory concentration (MIC) for 90% of isolates (80 microg/mL) and > 10 times the MIC breakpoint (160 microg/mL) of amikacin-susceptible bacteria reported to cause septic arthritis in horses. These values were attained for both joints for both techniques. Esmarch tourniquets prevented detectable loss of amikacin to the systemic circulation for both techniques. CONCLUSIONS AND CLINICAL RELEVANCE Both techniques reliably achieved synovial fluid concentrations of amikacin consistent with concentration-dependent killing for bacteria commonly encountered in horses with septic arthritis. Esmarch tourniquets were effective for both delivery techniques in standing horses.

Osteochondral injury increases type II collagen degradation products (C2C) in synovial fluid of Thoroughbred racehorses

OBJECTIVES To investigate the effects of exercise and osteochondral (OC) injury on type II collagen degradation products (collagenase cleavage neoepitope commercially known as C2C) in synovial fluid (SF) from Thoroughbred (TB) racehorses and to compare these results with radiographic and arthroscopic scores of severity of joint injury. METHODS Metacarpophalangeal/metatarsophalangeal (MCP/MTP) and carpal SF was obtained from (1) 20 normal rested horses, (2) the same horses after 5 to 6 months of race training, and (3) 27 horses with OC injury from racing. For group 3, radiographic and arthroscopic scores were determined. Concentrations of SF C2C were determined by ELISA. RESULTS SF C2C concentrations in OC injured carpal and MCP/MTP joints were significantly different than rested and exercised joints (P<0.01). However, carpal and MCP/MTP SF C2C concentrations were not significantly different between rested and exercised groups. Arthroscopic scores were significantly higher for OC injured carpal than OC injured MCP/MTP joints (P=0.002). OC injured SF C2C concentrations were positively correlated with radiographic and arthroscopic scores. Arthroscopic scores were positively correlated with radiographic scores. SF C2C concentrations >or= 64 pmol/mL for MCP/MTP joints and >or= 75 pmol/mL for carpal joints discriminated OC injured joints from rested or exercised joints. CONCLUSION OC injury caused a significant increase in SF C2C concentrations in carpal and MCP/MTP joints compared to rested and exercised horses. SF C2C concentrations were correlated to severity of joint injury. Based on these findings, SF C2C analysis may be useful for evaluation of joint injury.

PYTHIOSIS IN A DROMEDARY CAMEL (CAMELUS DROMEDARIUS)

Abstract A 4.5-yr-old male dromedary camel (Camelus dromedarius) was evaluated for a mass on the right side of the face. A complete blood count and blood chemistry revealed anemia and hypoproteinemia. Radiographs did not reveal bony involvement. The mass was resected and Pythium insidiosum was cultured. The camel was treated with an experimental immunotherapeutic vaccine and with sodium iodide and ceftiofur. The camel began to lose weight postoperatively and died 6 mo later. At necropsy, the camel was found to have gastritis of the third compartment of the stomach with intralesional hyphae of this oomycete pathogen.

Prevalence of various presale radiographic findings and association of findings with sales price in Thoroughbred yearlings sold in Kentucky

OBJECTIVE To estimate prevalences of various presale radiographic findings and of presale arthroscopy in horses offered for sale at the 2006 Keeneland September yearling sale and to compare sales prices between yearlings with and without various presale radiographic findings or a history of arthroscopy. ANIMALS 397 Thoroughbred yearlings. DESIGN Cross-sectional study. PROCEDURES Presale radiographs and health records were examined to estimate prevalences of various radiographic findings and presale arthroscopy. Sales price records were used to compare sales prices between yearlings with and without various presale radiographic findings or a history of arthroscopy. RESULTS In the forelimbs, the most common radiographic findings were vascular channels in the proximal sesamoid bones (23%), enthesophytes or osteophytes in the radiocarpal joint (22%), and osteochondritis lesions involving the sagittal ridge of the third metacarpal bone (20%). In the hind limbs, the most common radiographic findings were enthesophytes or osteophytes involving the proximal sesamoid bones (39%), abnormalities of the distodorsal aspect of the third metatarsal bone (36%), enthesophytes or osteophytes involving the distal intertarsal joint (27%), and osteochondritis lesions involving the stifle joint (8%). Thirteen percent of horses had a history of presale arthroscopy. Median sales price was significantly lower in horses with fragments of the proximal phalanx than in horses without. Median sales price was significantly higher in horses with a history of presale arthroscopy than in horses without. CONCLUSIONS AND CLINICAL RELEVANCE Results revealed significant associations between a diagnosis of fragments of the proximal phalanx, presale arthroscopy, and sales price in Thoroughbred yearlings.

Associations of horse age, joint type, and osteochondral injury with serum and synovial fluid concentrations of type II collagen biomarkers in Thoroughbreds.

OBJECTIVE To determine the effects of horse age, osteochondral injury, and joint type on a synthesis biomarker and 3 degradative biomarkers of type II collagen in Thoroughbreds. ANIMALS Healthy rested adult (3- to 12-year-old) Thoroughbreds (n = 19), yearling (1- to 2-year-old) Thoroughbreds (40), and Thoroughbred racehorses (2 to 7 years old) undergoing arthroscopic surgery for removal of osteochondral fragments that resulted from training or racing (41). PROCEDURES Samples of blood and metacarpophalangeal, metatarsophalangeal, or carpal joint synovial fluid (SF) were collected from all horses. Commercially available assays were used to analyze SF and serum concentrations of type II collagen biomarkers of synthesis (carboxy propeptide of type II collagen [CPII]) and degradation (cross-linked C-telopeptide fragments of type II collagen [CTX II], neoepitope generated by collagenase cleavage of type I and II collagen [C1,2C], and neoepitope generated by collagenase cleavage of type II collagen [C2C]). RESULTS Osteochondral injury affected concentrations of CPII, CTX II, C1,2C, and C2C in SF, serum, or both, compared with concentrations in healthy adult horses. Compared with adult horses, yearling horses had increased SF or serum concentrations of degradative biomarkers (CTX II, C1,2C, and C2C). Concentrations were higher in carpal than metacarpophalangeal or metatarsophalangeal joints for all biomarkers in osteochondral-injured horses. Variable differences in SF concentrations between joint types were detected in healthy adult and yearling horses. CONCLUSIONS AND CLINICAL RELEVANCE Horse age, osteochondral injury, and joint type all significantly affected type II collagen biomarker concentrations in SF and serum of Thoroughbreds.

Lameness, athletic performance, and financial returns in yearling Thoroughbreds bought for the purpose of resale for profit.

OBJECTIVE To characterize lameness during training and compare exercise variables and financial returns among yearling Thoroughbreds that were bought for the purpose of resale for profit. ANIMALS 40 yearling Thoroughbreds. DESIGN Prospective study. PROCEDURES Horses purchased at yearling sales (summer 2004) were trained prior to resale at 2-year-olds in training sales (spring 2005). Horses were monitored daily for diagnosis and treatment of lameness during training. Selected variables, including sex, age, purchase price, lameness, distance (No. of furlongs) galloped during training, and financial returns, were compared among horses that had performance speeds (assessed at 2-year-olds in training sales) classified as fast, average, or slow. RESULTS 37 of 40 horses became lame during training, most commonly because of joint injury. Eighteen of the lame horses had hind limb injuries only; 5 horses had injuries in forelimbs and hind limbs. The frequency of new cases of lameness increased as the date of the 2-year-olds in training sales approached. At the sales, 4, 21, and 15 horses were classified as fast, average, or slow, respectively; median financial return was slightly (but significantly) different among horses classified as fast (

High-mobility group box chromosomal protein 1 as a potential inflammatory biomarker of joint injury in Thoroughbreds

14,000), average (

Regional and zonal variations in the sulfation patterns of chondroitin sulfate in normal equine corneal stroma.

0), or slow (-

Capillary zone electrophoresis for the determination of atovaquone in serum.

8,000). CONCLUSIONS AND CLINICAL RELEVANCE Incidence of lameness during training in yearling horses purchased for the purpose of resale for profit was high. Lameness more commonly affected hind limbs than forelimbs and was attributable to joint injury in most horses. Financial returns differed between horses classified as fast and average or slow at the 2-year-olds in training sales.