Pharmacokinetics of fentanyl delivered transdermally in healthy adult horses--variability among horses and its clinical implications

The safety and pharmacokinetics of fentanyl, delivered transdermally at a dosage of 60-67 microg/kg, were investigated in six healthy adult horses. Three transdermal fentanyl patches (Duragesic), each containing 10 mg of fentanyl citrate, were applied to the mid-dorsal thorax of each horse and left in place for 72 h. Plasma fentanyl concentrations were periodically measured throughout this period and for 12 h after patch removal. After an initial delay of approximately 2 h, the plasma fentanyl concentration rose rapidly in a fairly linear fashion, reaching a peak at around 12 h; thereafter, it gradually declined in a roughly linear manner over the next 72 h. There was much individual variation, however. The initial delay ranged from 0 to 5.1 h (mean, 1.91+/-2.0 h), Tcmax ranged from 8.5 to 14.5 h (mean, 11.4+/-2.7 h) and Cmax ranged from 0.67 to 5.12 ng/mL (mean, 2.77+/-1.92 ng/mL). In two horses, the plasma fentanyl concentration failed to reach even 1 ng/mL, whereas in the other four horses it was >1 ng/mL for at least 40 h and for at least 72 h in two of these horses. No adverse effects attributable to fentanyl were observed in any of the horses, indicating that this dosage is safe in systemically healthy adult horses. However, it failed to achieve plasma fentanyl concentrations generally considered to be analgesic (>or=1 ng/mL) in about one-third of horses.     

Optimization of an in vitro assay to detect Streptococcus equi subsp. equi

Streptococcus equi is the etiologic agent of a highly infectious upper respiratory disease of horses known as strangles. Bacterial culture methods and polymerase chain reaction (PCR) of nasopharyngeal washes and guttural pouch lavages are used routinely to test clinical and carrier animals for the presence of S. equi but no definitive or gold standard test method has been shown to be optimal. We hypothesized that (i) a flocked swab submerged in ten-fold serial dilution suspensions of S. equi prepared in 0.9% NaCl would detect more colony forming units (CFU) than a rayon swab when used to inoculate a blood agar plate, (ii) centrifugation of a 1ml aliquot of each suspension would improve the limit of detection (LOD) by bacterial culture and PCR compared to the culture or PCR of submerged swab samples, (iii) PCR of the centrifuged samples from each suspension would be more sensitive than aerobic culture alone, and (iv) PCR of a 1ml aliquot directly from a sample would be more sensitive than PCR of a sample following submersion of a flocked swab in 1ml saline. Using 7 ten-fold serial dilutions of S. equi in 0.9% NaCl, the LOD for 4 bacterial culture methods and 3 PCR methods were compared. The LOD of direct PCR and flocked swab culture was determined at 1cfu/ml. All PCR methods were equivalent to each other and were more sensitive than any of the culture methods at the lower dilutions. At higher cell densities (>100cfu/ml) flocked swab culture was not statistically better than rayon swab culture, but it was superior to all other methods tested.     

Association of Blood Lactate Concentration and Outcome in Foals

Background: Lactate concentration in blood or plasma ([LAC]) and change in [LAC] are associated with survival in sick foals. Hypothesis: [LAC] and change in [LAC] over time are associated with survival at 96 hours and discharge in neonatal foals. Furthermore [LAC] and change in [LAC] over time correlate with blood culture results and blood pressure at admission. Animals: Two hundred and twenty‐five foals consecutively admitted to a Neonatal Intensive Care Unit. Methods: Retrospective case review. Foals ≤30 days of age with [LAC] from arterial (190) or umbilical (35) blood gas analysis ([LAC]_BG) at admission, 24, and 48 hours. [LAC]_BG, blood pressure, blood culture status, and outcome (survival versus nonsurvival at 96 hours and discharge) were recorded. Change in [LAC]_BG over time ([LAC]_BGΔT) was calculated. Results: [LAC]_BG was lower in survivors (96 hours and discharge) at all times. [LAC]_BGΔT was larger for survivors (96 hours). Odds of survival (96 hours and discharge) decreased 18, 39, 53 and 22, 38, and 47%, respectively, at each sample time for every 1 mmol/L increment in [LAC]_BG and increased 156% for each 1.0/day increment in [LAC]_BGΔT from admission to 24 hours at 96 hours. Blood pressure and [LAC]_BG were not correlated (P= .196) until removal of selected foals (mean arterial pressure <60 mmHg, admission [LAC]_BG <5.5 mmol/L) (P < .001). Bacteremia was not associated with [LAC]_BG. Proposed admission [LAC]_BG cut‐points for future studies were 6.5 mmol/L (96 hours) and 5.5 mmol/L (discharge). Conclusions and Clinical Importance: Prospective studies evaluating [LAC], [LAC]_BGΔT, and cut‐points in sick foals are warranted.     

Lafora disease as a cause of visually exacerbated myoclonic attacks in a dog

An 8-year-old, castrated male, miniature wire-haired dachshund was presented with a 4-month history of intermittent facial twitching (myoclonus). The myoclonic episodes progressed over a 16-month period. Generalized seizure activity was infrequent. Clinical examination revealed visually stimulated myoclonus. Response to therapy with antiepileptic drugs was equivocal. Genetic testing identified the dog as being affected by Lafora disease.     

Surgical and nonsurgical management of sagittal slab fractures of the third carpal bone in racehorses: 32 cases (1991-2001)

OBJECTIVE: To compare results (ie, return to racing and earnings per race start) of surgical versus nonsurgical management of sagittal slab fractures of the third carpal bone in racehorses. DESIGN: Retrospective study. ANIMALS: 32 racehorses (19 Thoroughbreds, 11 Standardbreds, and 2 Arabians). PROCEDURE: Medical records and radiographs were reviewed to obtain information regarding signalment and treatment. Follow-up information was obtained from race records. Robust regression analysis was performed to evaluate earnings per start in horses that raced at least once before and after injury. RESULTS: 22 (69%) horses raced at least once after treatment of the fracture. All 7 horses treated by means of interfragmentary compression raced after treatment, and horses that underwent interfragmentary compression had significantly higher earnings per start after the injury than did horses treated without surgery. Eight of 9 horses treated by means of arthroscopic debridement of the damaged cartilage and bone raced after treatment, but only 7 of 16 horses treated without surgery (ie, stall rest) were able to return to racing after treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that racehorses with sagittal slab fractures of the third carpal bone have a favorable prognosis for return to racing after treatment. Horses treated surgically were more likely to race after treatment than were horses treated without surgery.     

Effects of insulin-like growth factor-II on the mitogenic and metabolic activities of equine articular cartilage with and without interleukin 1-beta

OBJECTIVE: To investigate the effects of insulin-like growth factor-II (IGF-II) on DNA and glycosaminoglycan (GAG) synthesis and the expression of matrix-related genes in equine articular cartilage explants and chondrocytes, respectively, with and without interleukin 1-beta (IL1-beta). SAMPLE POPULATION: Articular cartilage from 12 adult horses. PROCEDURE: Articular cartilage was incubated in standard media with and without equine IL1-beta (10 ng/mL) containing various concentrations of IGF-II for 72 hours. Synthesis of DNA and GAG was determined by incorporation of thymidine labeled with radioactive hydrogen (3H) and sulfate labeled with radioactive sulfur (35S), respectively. Total GAG content of the explants and spent media was determined by use of the 1,9-dimethylmethylene blue assay. Northern blots of RNA from cultured equine articular cartilage chondrocytes were hybridized with cDNA of major matrix molecules. RESULTS: Insulin-like growth factor-II stimulated DNA and GAG synthesis at concentrations of 25 and 50 ng/mL, respectively. In cartilage explants conditioned with IL1-beta, IGF-II stimulated DNA and GAG synthesis at concentrations of 500 and 50 ng/mL, respectively. Insulin-like growth factor-II had no effect on total GAG content as determined by the 1,9-dimethylmethylene blue assay. No specific effects on steady-state levels of messenger RNAs were observed. CONCLUSIONS AND CLINICAL RELEVANCE: Insulin-like growth factor-II stimulated DNA and GAG synthesis in equine adult cartilage and may have potential application in vivo.     

Endoscopic evaluation of the gastroduodenal mucosa to determine the safety of short-term concurrent administration of meloxicam and dexamethasone in healthy dogs

OBJECTIVE: To evaluate the safety, with respect to the development of gastric ulcers and erosions, of concurrent administration of meloxicam and dexamethasone for 3 days to healthy dogs. ANIMALS: 20 conditioned purpose-bred research Beagles. PROCEDURE: Seven days prior to treatment, dogs were anesthetized for endoscopic evaluation of the upper portion of the gastrointestinal tract (ie, the gastric and duodenal mucosa). Five regions of the gastroduodenal area were scored by 2 investigators. Dogs were randomly assigned to 1 of 4 treatment groups as follows: saline-saline, dexamethasone-saline, saline-meloxicam, and dexamethasone-meloxicam groups. On days 1, 2, and 3, dogs received either dexamethasone or saline (0.9% NaCl) solution injections SC twice daily. On days 2, 3, and 4, dogs received either meloxicam or saline solution injections SC once daily. On day 2, dogs were anesthetized for a sham surgery (ie, electrostimulation). On day 5, the gastroduodenal area of each dog was reevaluated by use of endoscopic evaluation and histologic examination of biopsy specimens. RESULTS: The total endoscopic score of the dexamethasone-meloxicam group was significantly greater than the scores of the other groups. The dexamethasone-saline group had a mean cumulative score that was significantly greater than the saline-meloxicam or saline-saline groups. Endoscopic scores of the saline-meloxicam group were not significantly different from scores of the saline-saline group. No significant differences in histologic findings were found between groups. CONCLUSIONS AND CLINICAL RELEVANCE: In healthy dogs, meloxicam appears to be safe with regard to adverse effects on the gastrointestinal tract. Concurrent administration of dexamethasone and meloxicam is more likely to cause gastric erosions than meloxicam administration alone.     

A comparison of ultra-high-molecular weight polyethylene cable and stainless steel wire using two fixation techniques for repair of equine midbody sesamoid fractures: an in vitro biomechanical study

OBJECTIVE: To compare the monotonic tensile and fatigue strength of 16-gauge stainless steel wire (SSW) to ultra-high-molecular weight polyethylene (UHMWPE) cable using a transfixed cerclage technique in an in vitro midbody sesamoid osteotomy model. Endoscopic modifications to Martins transfixed cerclage technique were developed. A new suture technique of fixation was compared with the transfixed cerclage technique by measuring gap formation after cyclic testing. STUDY DESIGN: An in vitro biomechanical paired equine cadaver limb study. SAMPLE POPULATION: Twenty-one paired cadaveric adult equine forelimbs. METHODS: Uniaxial medial midbody sesamoid osteotomies were created in paired adult equine forelimbs. Monotonic tensile strength was measured on 10 forelimbs repaired by a transfixed cerclage technique using wire or cable. Fatigue testing to failure was performed on 4 forelimbs repaired using the transfixed cerclage technique by cycling the limbs between 500 N and 2,000 N. The limbs were initially repaired with wire, cycled until the wire broke, then repaired with cable and cycled again to failure. Fatigue testing for gap displacement was performed on 8 limbs repaired with either the transfixed cerclage technique or the suture technique. Limbs were cycled between 500 N and 2,000 N for 10,000 cycles. The limbs were repaired with wire initially, tested, and then repaired with cable and tested again. Twenty-two limbs were used for mechanical testing. The remaining limbs (20) were used to develop and practice the endoscopic transfixed cerclage (10 limbs) and suture (10 limbs) techniques. RESULTS: Ultimate tensile strength (UTS) of UHMWPE cable constructs was 34% greater than the UTS of SSW constructs. Fatigue strength was 2 to 20 times greater for UHMWPE cable constructs than SSW constructs. Separation of fragments was 153% less for limbs repaired by the suture technique compared with those repaired by the transfixed cerclage technique. CONCLUSIONS: UHMWPE cable shows promise for this clinical application because of its greater tensile and fatigue strength. The newly described suture technique significantly reduced gap formation compared with the transfixed cerclage technique. Osteotomy gap formation occurred early in cycling, suggesting that rigid support in the form of a cast may be needed during the early postoperative period for wiring techniques. CLINICAL RELEVANCE: Clinical testing of UHMWPE cable should eliminate problems of wire breakage seen with SSW. The endoscopic transfixed cerclage technique can be used by surgeons familiar with arthroscopic surgery. However, the suture technique needs to be tested in vivo to determine whether there is a clinical advantage compared with the transfixed cerclage technique.