Penetration of ceftiofur into sterile vs. Mannheimia haemolytica-infected tissue chambers in beef calves after subcutaneous administration of ceftiofur crystalline free acid sterile suspension in the ear pinna

The effect of Mannheimia haemolytica infection on the penetration of ceftiofur and desfuroylceftiofur metabolites into tissue chambers was studied in cattle after subcutaneous administration of ceftiofur crystalline free acid sterile suspension (CCFA-SS). Four tissue chambers were implanted subcutaneously in each of 12 calves. Approximately 45 days after implantation, two chambers were inoculated with M. haemolytica (10(6) colony-forming units per chamber) while the remaining two chambers were inoculated with sterile phosphate-buffered saline. Twenty-four hours after inoculation, CCFA-SS was administered subcutaneously in the middle third of the caudal ear pinna of each calf. Chamber fluid and blood samples were collected at predetermined times for 10 days following dosing and analyzed for ceftiofur and desfuroylceftiofur metabolites by high-performance liquid chromatography. Concentrations of ceftiofur and desfuroylceftiofur metabolites in plasma and tissue chamber fluid remained above a threshold of 0.2 microg/mL for at least 8 days. Infected tissue chamber fluid concentrations of ceftiofur and desfuroylceftiofur metabolites were significantly higher than those in non-infected tissue chamber fluid, which correlated with significantly higher total protein concentration in infected tissue chambers. These results indicate that single subcutaneous administration of CCFA-SS at 6.6 mg/kg can be expected to provide effective therapy of susceptible bacterial infections for a period of at least 1 week.     

Effect of dietary fat on oral bioavailability of tepoxalin in dogs

A pharmacokinetic study was conducted to compare the oral bioavailability of tepoxalin and its pharmacologically active acid metabolite in fasted dogs and dogs fed either a low-fat or high-fat commercial diet. Using a cross-over design, six beagles were administered tepoxalin (10 mg/kg) intravenously (i.v.) and orally (p.o.) after being fed one of three diets (fasted, low-fat, or high-fat). Thereafter, blood samples were collected at frequent intervals, concentrations of tepoxalin and acid metabolite in plasma were determined by high performance liquid chromatography, and pharmacokinetic parameters were estimated. After i.v. dosing, the mean (+/-SD) half-life of elimination (t(1/2(beta))) was 2.45 +/- 1.47 h. After p.o. administration, plasma concentrations of acid metabolite were consistently higher than corresponding concentrations of the parent tepoxalin, indicating that tepoxalin is subject to a substantial first-pass effect. Mean (+/-SD) peak concentrations of tepoxalin were significantly higher after feeding of low-fat (1.08 +/- 0.37 microg/mL) and high-fat (1.19 +/- 0.29 microg/mL) diets than in fasted dogs (0.53 +/- 0.20 microg/mL), suggesting that feeding improves oral bioavailability.     

Ocular penetration of oral doxycycline in the horse

OBJECTIVE: To investigate intraocular penetration of orally administered doxycycline in the normal equine eye and to compare intraocular and serum doxycycline concentrations. Procedures Six mares were administered doxycycline at 10 mg/kg every 12 h by nasogastric tube for 5 days. Blood, aqueous, and vitreous samples were collected on days 1 and 5. All samples were assayed for doxycycline concentrations. Aqueous and vitreous samples were also assayed for protein quantitation. RESULTS: Doxycycline was rapidly absorbed after the first dose (T(max) value of 1.42 +/- 1.28 h); and elimination of doxycycline occurred slowly (median t(1/2) = 10.88 h). Doxycycline could not be detected in the aqueous on days 1 and 5, nor could it be detected in the vitreous on day 1. On day 5, the mean vitreous doxycycline concentration was 0.17 +/- 0.04 microg/mL at 2 h after drug administration. CONCLUSIONS: Repeated oral administration of doxycycline in the horse resulted in steady state serum concentrations of < 1 microg/mL; however, it did not result in appreciable concentrations of drug in the aqueous and vitreous in normal eyes.     

Surgical management of acute ear canal separation in a cat

A 5-year-old cat presented with haemorrhagic left aural discharge, 2 days following a road traffic accident. Otoscopic examination identified disruption of the external ear canal at the auricular/annular cartilage junction. This was managed by total ear canal ablation and lateral bulla osteotomy. Left sided facial nerve deficits were present following surgery. Eighteen months postoperatively there were no auricular problems, however facial nerve deficits persisted. There are no previous reports describing management of acute separation at the auricular/annular cartilage junction of the external ear in the cat or dog. This case report describes the presentation, diagnosis and surgical management of an acute ear canal separation at the auricular/annular junction of the external ear canal in a cat.     

Treatment of canine and feline diaphyseal radial and tibial fractures with low-stiffness external skeletal fixation

The healing of 62 cases of radial and tibial fractures treated with low-stiffness Kirschner-Ehmer external skeletal fixation frames (frame types 1a, 1a plus intramedullary pin [1aIMP], 1b and 2b) was evaluated. The mean time to clinical union was 65 days. All cases treated with 1b, 2b or 1aIMP frames healed. Four of 25 cases treated with 1a frames failed to heal due to premature pin loosening; these failures were in heavier patients than 1a cases which healed (P=0.041). Complications occurred in 40 of 62 cases, and were more common in cases treated with type 2b frames. Pin loosening was the most frequent complication (35 cases) and most commonly involved the most proximal pin (P<0.001). In type 2b frames, full pins loosened more frequently than half pins (P<0.001). This study indicates that canine and feline fractures can heal readily when treated with these frames, suggesting that more rigid type 2a or type 3 frames are unnecessary in the majority of cases. Increased morbidity compared with the use of more rigid frames need not be expected, but 1a frames should be avoided in heavier patients.     

Medetomidine-ketamine anaesthesia induction followed by medetomidine-propofol in ponies: infusion rates and cardiopulmonary side effects

REASONS FOR PERFORMING STUDY: To search for long-term total i.v. anaesthesia techniques as a potential alternative to inhalation anaesthesia. OBJECTIVES: To determine cardiopulmonary effects and anaesthesia quality of medetomidine-ketamine anaesthesia induction followed by 4 h of medetomidine-propofol anaesthesia in 6 ponies. METHODS: Sedation consisted of 7 microg/kg bwt medetomidine i.v. followed after 10 min by 2 mg/kg bwt i.v. ketamine. Anaesthesia was maintained for 4 h with 3.5 microg/kg bwt/h medetomidine and propofol at minimum infusion dose rates determined by application of supramaximal electrical pain stimuli. Ventilation was spontaneous (F(I)O2 > 0.9). Cardiopulmonary measurements were always taken before electrical stimulation, 15 mins after anaesthesia induction and at 25 min intervals. RESULTS: Anaesthesia induction was excellent and movements after pain stimuli were subsequently gentle. Mean propofol infusion rates were 0.89-0.1 mg/kg bwt/min. No changes in cardiopulmonary variables occured over time. Range of mean values recorded was: respiratory rate 13.0-15.8 breaths/min; PaO2 29.1-37.9 kPa; PaCO2 6.2-6.9 kPa; heart rate 31.2-40.8 beats/min; mean arterial pressure 90.0-120.8 mmHg; cardiac index 44.1-59.8 ml/kg bwt/min; mean pulmonary arterial pressure 11.8-16.4 mmHg. Recovery to standing was an average of 31.1 mins and ponies stood within one or 2 attempts. CONCLUSIONS: In this paper, ketamine anaesthesia induction avoided the problems encountered previously with propofol. Cardiovascular function was remarkably stable. Hypoxaemia did not occur but, despite F(I)O2 of > 0.9, minimal PaO2 in one pony after 4 h anaesthesia was 8.5 kPa. POTENTIAL RELEVANCE: The described regime might offer a good, practicable alternative to inhalation anaesthesia and has potential for reducing the fatality rate in horses.     

Comparison of results of three commercial heartworm antigen test kits in dogs with low heartworm burdens

OBJECTIVE: To compare results of 3 commercial heartworm antigen test kits performed on serum samples from dogs infected with low numbers of adult female heartworms. DESIGN: Blinded laboratory evaluation. Sample Population-Serum samples from dogs (n = 208) proven at necropsy to be infected with 1 to 4 adult female heartworms and from dogs (32) without heartworms. PROCEDURE: Samples were sequentially tested with each test kit, following the manufacturers' instructions, by licensed veterinary technicians in private practice who were not aware of infection status of the dogs. The order of test kit evaluations was randomly chosen. For each test kit, sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were evaluated. RESULTS: All tests yielded some false-negative results, and there were significant differences among tests in regard to ability to detect low heartworm burdens. Sensitivity of the test kits ranged from 78 to 84%. For all test kits, sensitivity increased as number of female heartworms increased. All 3 test kits had high specificity (97%). CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that sensitivity of the 3 commercially available heartworm antigen test kits ranged from 78 to 84% when used to test serum samples from dogs with low heartworm burdens, and that sensitivity varied among test kits. For all 3 test kits, specificity was 97%. All 3 test kits yielded false-positive and false-negative results for some dogs with low heartworm burdens.     

Studies on the Putative Interactions between the Organophosphorus Insecticide Phosmet and Recombinant Mouse PrP and its Implication in the BSE Epidemic

It has been suggested that exposure of cattle to the ectoparasiticide Phosmet in the 1980s caused a conformational change in the cellular prion protein (PrP^C) to form the BSE prion (PrP^SC), which initiated the epidemic of bovine spongiform encephalopathy (BSE).Recombinant mouse cellular prion (r[mouse]PrP^C) was exposed to the organophosphorus pesticide Phosmet in vitro and the conformation of the prion before and after exposure was monitored using circular dichroism (CD) spectroscopy, utilizing synchrotron radiation at the Council for the Central Laboratory of the Research Councils (CLRC) facilities at Daresbury, UK. Metabolites of Phosmet, generated in situ by rat microsomes, were investigated in the same way, to determine whether they might initiate the conformational change due to their high chemical reactivity.Our studies showed that exposure of r[mouse]PrP^C to Phosmet or microsomes-generated metabolites of Phosmet did not result in the conformational change in the protein from -helix to -pleated sheet that is characteristic of the PrP^C to PrP^SC conversion and, therefore, Phosmet is very unlikely to have initiated the BSE epidemic by a simple direct mechanism of conformational change in the prion protein.     

Ultrastructural characterization of apoptosis in bovine lymphocytes exposed to Pasteurella haemolytica leukotoxin

OBJECTIVE: To characterize ultrastructural changes of bovine lymphocytes exposed to Pasteurella haemolytica leukotoxin (LKT). SAMPLE POPULATION: Partially purified LKT from a wild type P. haemolytica A1 strain and inactive pro-LKT from an isogeneic mutant Phaemolytica strain. Isolated bovine lymphocytes were obtained from 2 healthy calves. PROCEDURE: Isolated bovine lymphocytes were incubated with various concentrations of LKT and pro-LKT for 3 hours at 37 C and examined by use of transmission electron microscopy. A cytochemical Klenow DNA fragmentation assay was used to examine lymphocytes for DNA fragmentation. RESULTS: Lymphocytes incubated with LKT at a high concentration (1.0 toxic U/ml) had ultrastructural evidence of cytoplasmic and nuclear membrane rupture and swelling or lysis of mitochondria. Low concentrations of leukotoxin (0.1 toxic U/ml) induced DNA fragmentation in 80% of lymphocytes. Ultrastructurally, these cells had nuclear membrane blebbing, cytoplasmic vaculation, chromatin condensation, nuclear fragmentation, and membrane-bound apoptotic bodies. Incubation of lymphocytes with LKT at extremely low concentrations (0.001 toxic U/ml) or with pro-LKT did not alter their ultrastructure. Inclusion of 0.5 mM ZnCl2 in the medium blocked leukotoxin-induced ultrastructural changes in bovine lymphocytes. CONCLUSIONS AND CLINICAL RELEVANCE: Low concentrations of LKT induce apoptosis and high concentrations induce oncotic cell lysis in bovine lymphocytes. The ability of low LKT concentrations to induce apoptosis in host leukocytes may allow bacteria to escape host immune surveillance and colonize the host.