In vitro effects and in vivo efficacy of a novel cyclooxygenase-2 inhibitor in dogs with experimentally induced synovitis

OBJECTIVE: To determine cyclooxygenase-2 (COX-2) selectivity, pharmacokinetic properties, and in vivo efficacy of ML-1,785,713 in dogs. ANIMALS: 21 healthy male and female mixed-breed dogs and 24 healthy male Beagles. PROCEDURE: Selectivity of ML-1,785,713 for inhibiting COX-2 was determined by comparing the potency for inhibiting cyclooxygenase-1 (COX-1) with that of COX-2 in canine blood. Pharmacokinetic properties were determined after i.v. (2 mg/kg) and oral (8 mg/kg) administration in female mixed-breed dogs. In vivo efficacy was evaluated in male mixed-breed dogs with urate crystal-induced synovitis. Prophylactic efficacy was evaluated by administering ML-1,785,713 two hours before induction of synovitis whereas therapeutic efficacy was determined by administering ML-1,785,713 one hour after induction of synovitis. RESULTS: Blood concentrations that resulted in 50% inhibition of COX-1 and COX-2 activity in vitro were 119.1 microM and 0.31 microM, respectively, and selectivity ratio for inhibiting COX-2 relative to COX-1 was 384. ML-1,785,713 had high oral bioavailability (101%), low systemic clearance (77 mL/min/kg), and an elimination half-life of 5.9 hours. ML-1,785,713 was efficacious when administered prophylactically and therapeutically to dogs with urate crystal-induced synovitis. CONCLUSIONS AND CLINICAL RELEVANCE: ML-1,785,713 is a novel, potent COX-2 inhibitor that is the most selective COX-2 inhibitor described for use in dogs to date. ML-1,785,713 has oral bioavailability and low systemic clearance that is comparable to other non-steroidal anti-inflammatory drugs. It is effective after prophylactic and therapeutic administration in attenuating lameness in dogs with urate crystal-induced synovitis. Drugs that specifically inhibit COX-2 and not COX-1 at therapeutic doses may have an improved tolerability profile, compared with nonselective non-steroidal anti-inflammatory drugs.     

Ear cleaning: the UK and US perspective

Ear cleaning helps maintain the normal otic environment and is important in the treatment of otitis. Over cleaning, however, may trigger otitis through maceration of the epidermal lining. Simple manual cleaning is useful for routine cleansing but doesn't remove tightly adherent debris. Bulb syringes are more vigorous but may damage the ear in inexperienced hands. Devices using mains water pressure or dental machines are also available. Thorough cleaning of the ear canals and middle ear cavity can only be achieved by retrograde flushing using specially adapted catheters, feeding tubes or video otoscopes under anaesthesia. Myringotomy, inspection and cleaning of the middle should be performed if the tympanic membrane appears abnormal. There are a wide variety of cleaning fluids available. Ceruminolytics soften and dissolve cerumen to facilitate cleaning. Surfactants emulsify debris, breaking it up and keeping it in solution. Astringents dry the ear canal surface, preventing maceration. Maintaining a low pH and incorporating antimicrobial agents can inhibit microbial proliferation and glucocorticoids can be used to reduce inflammation. Adverse effects and contraindications following ear cleaning can include maceration, contact reactions, otitis media, ear canal avulsion, vestibular syndrome, Horner's syndrome, facial nerve paralysis and deafness. Care should be exercised in selecting cleaning fluids if the tympanic membranes are ruptured.     

The influence of high-nitrogen forages on the voluntary feed intake of sheep

The objective of this research was to examine the effect of high concentrations of nonprotein nitrogen (NPN) on the voluntary food intake of sheep fed high-quality grasses. Wether lambs (n = 6 per treatment) were fed dried switchgrass (Panicum virgatum L.; Exp. 1) or dried tall fescue (Festuca arundinacea Schreb.; Exp. 2). In both experiments, urea was added to the dried forage at 0 (control), 12, or 24 g of N/kg of DM to increase the NPN concentration. Acid detergent fiber concentrations were 305 g/kg of DM in both experiments, although DM digestibility was 663 and 618 g/ kg of DM in Exp. 1 and Exp. 2, respectively. Voluntary feed intake of the control forage was 28.2 and 19.1 g/ kg of BW in Exp. 1 and Exp. 2, respectively, and decreased for the high-urea treatments to 25.2 and 16.2 g/kg of BW in Exp. 1 (P = 0.07) and Exp 2 (P = 0.03), respectively. Total feed N concentrations increased from 29.5 g to 45.7 g of N/kg of DM in Exp. 1 (P < 0.01) and from 28.4 to 55.9 g of N/kg of DM in Exp. 2 (P < 0.01). Nonprotein N concentrations increased from 28.3 to 53.8% of the total N in switchgrass diets (Exp. 1; P < 0.01), and from 26.4 to 64.0% in tall fescue diets (Exp. 2; P < 0.01). Plasma urea concentrations of the lambs increased from 3.1 to 6.6 mM (Exp. 1; P < 0.01) and from 2.9 to 5.8 mM (Exp. 2; P < 0.01) as the amount of urea added to the diets increased. These changes resulted in an increase in plasma osmolality from 298 to 307 mOsm/kg (Exp. 1; P = 0.04), and from 299 to 307 mOsm/kg (Exp. 2; P = 0.06). Increasing feed N and NPN concentrations through the addition of urea caused a significant decrease in the voluntary feed intake of sheep fed tall fescue and switchgrass. These responses showed no significant cause-and-effect relationship between voluntary feed intake, plasma urea concentrations, and plasma osmolality.     

Bilateral mandibular dentigerous cysts in a dog

Cysts in the dental cavities of dogs are rare. This report documents the case of a young boxer that was referred after having had treatment for bilateral oral swellings. Dentigerous cysts were tentatively diagnosed. Surgery was performed to aspirate the fluid and remove the first premolars, which were positioned in the cysts. Histopathological examination of tissue collected during the surgical procedure confirmed the diagnosis.     

Serum insulin concentrations in horses with equine Cushing's syndrome: response to a cortisol inhibitor and prognostic value

REASONS FOR PERFORMING STUDY: Serum insulin concentration and its use as a prognostic indicator in horses with equine Cushing's syndrome (ECS) have been poorly documented. OBJECTIVES: To examine daily insulin variations in horses with ECS and the effect of treatment using trilostane, a competitive inhibitor of 3beta-hydroxysteroid dehydrogenase. Further, we aimed to examine the relationship between baseline serum insulin concentration and survival in horses with ECS. METHODS: Basal serum insulin concentrations were measured in 20 confirmed ECS cases by taking blood at regular 4 h intervals for 24 h (1200, 1600, 2000, 2400, 0400 and 0800 h) before treatment (Day 0) and 10 days, and 30 days and 1-2 years after the onset of trilostane therapy. The temporal pattern of insulin was analysed using a linear mixed model approach, and the prognostic value of measurements on Day 0 assessed using receiver-operating characteristic analysis. RESULTS: Horses with ECS showed a diurnal pattern of serum insulin concentration, highest value at 1200 h, and this pattern was not altered by treatment with trilostane. Furthermore, despite a mild increase of serum insulin concentrations after 10 days of trilostane therapy, insulin concentration was unaffected in the long-term. Low serum insulin concentrations at the beginning of the trial were significantly associated with improved survival to 1-2 years. The 1200 h sampling before treatment had the highest prognostic value for prediction of survival with a sensitivity and specificity of at least 90% for serum insulin at < 62 and > 188 microu/ml to predict survival and nonsurvival, respectively. CONCLUSIONS AND POTENTIAL RELEVANCE: Insulin is a useful prognostic indicator for ECS, but potentially large variations can occur throughout a 24 h period, indicating a single sample may not be representative. Serum insulin concentration did not increase over 1-2 years in horses receiving trilostane therapy.     

Incidence of post-anaesthetic arrhythmias in dogs

OBJECTIVES: To assess the use of Holter monitoring for evaluating the incidence of post-anaesthetic cardiac arrhythmias and associated anaesthetic risk for two different anaesthetic protocols. METHODS: Patients undergoing orthopaedic surgery were randomly divided into two groups with different anaesthetic regimens (group A, isoflurane n = 30; group B, propofol n = 30). Two 24-hour Holter recordings were performed for each patient: the first directly following anaesthesia and the second, as a comparison, on the fifth postoperative day. RESULTS: Although all dogs were healthy on pre-anaesthetic cardiac evaluation, 56 dogs showed arrhythmias in the two 24-hour (Holter) electrocardiograms performed. However, the number of arrhythmias recorded was low in most cases (less than 10 supraventricular extrasystoles and less than 100 ventricular extrasystoles). One patient in group A showed 94 supraventricular extrasystoles during the second monitoring period. Three patients in each group developed more than 100 ventricular extrasystoles during both Holter recordings. There were no statistically significant differences between the two anaesthetic regimens or between the two recordings in both groups. CLINICAL SIGNIFICANCE: The two anaesthetic protocols investigated in this study did not induce an increased incidence of severe arrhythmias in healthy dogs in the post-anaesthetic phase.     

Retrospective study of bacterial infective arthritis in 31 dogs

OBJECTIVES: To characterise the presenting signs and pathological changes of canine bacterial infective arthritis in 31 dogs, and to document the response to different treatment regimens. Risk factors that may predispose joints to bacterial infective arthritis and influence the success of treatment were also investigated. METHODS: A retrospective review of cases of bacterial infective arthritis that were presented to three university veterinary referral hospitals over a five-year period (January 1997 to January 2002) was performed. RESULTS: The elbow joint (38 per cent) and stifle joint (44 per cent) were most commonly affected. Radiographic changes consistent with pre-existing osteoarthritis were identified in 14 joints, which had no history of previous surgery (articular or periarticular) or penetrating wound. No significant difference (P = 0.78) was identified between the outcome of combined surgical and medical management, and medical management alone. There were trends for poorer outcomes with increased bodyweight of the dog, longer duration of lameness and a higher nucleated cell count of the affected joint fluid at presentation. The overall infection rate for articular surgical procedures at one institution was 1-3 per cent. CLINICAL SIGNIFICANCE: Medical and/or surgical management were usually successful in resolving infection (94 per cent). However, they were frequently unsuccessful in restoring full joint function; this may in part have been due to the nature of the underlying joint