In Vivo confocal endomicroscopy of small intestinal mucosal morphology in dogs

Background: Confocal endomicroscopy (CEM) is an endoscopic technology that permits in vivo cellular and subcellular imaging of the gastrointestinal mucosa. Objective: To determine the feasibility of CEM to evaluate small intestinal mucosal topologic morphology in dogs and to characterize the appearance in healthy dogs. Animals: Fourteen clinically healthy research colony dogs. Methods: Experimental study. Dogs were anesthetized for standard endoscopic evaluation of the small intestine followed by CEM. Two fluorophores were used to provide contrast: fluorescein (10% solution, 15 mg/kg IV) before administration of topical acriflavine (0.05% solution) via an endoscopy spray catheter. A minimum of 5 sites within the small intestine were assessed and at each location, sequential adjustment of imaging depth allowed collection of a three-dimensional volume equivalent to an 'optical biopsy'. CEM-guided pinch biopsies were obtained for histologic examination. Results: CEM provided high-quality in vivo cellular and subcellular images. Intravenous administration of fluorescein provided sufficient contrast to allow assessment of the vasculature, cellular cytoplasmic features and goblet cell numbers, and distribution. Topical application of acriflavine preferentially stained cellular nucleic acids, allowing evaluation of nuclear morphology. Quality of captured images was occasionally affected by motion artifact, but improved with operator experience. Conclusion and Clinical Importance: CEM provides in vivo images that allow for cellular and subcellular assessment of intestinal mucosal morphology during endoscopy. This has implications for aiding in vivo diagnosis of gastrointestinal disease. \ua9 2013 by the American College of Veterinary Internal Medicine

Treatment of mastitis during lactation

Treatment of mastitis should be based on bacteriological diagnosis and take national and international guidelines on prudent use of antimicrobials into account. In acute mastitis, where bacteriological diagnosis is not available, treatment should be initiated based on herd data and personal experience. Rapid bacteriological diagnosis would facilitate the proper selection of the antimicrobial. Treating subclinical mastitis with antimicrobials during lactation is seldom economical, because of high treatment costs and generally poor efficacy. All mastitis treatment should be evidence-based, i.e., the efficacy of each product and treatment length should be demonstrated by scientific studies. Use of on-farm written protocols for mastitis treatment promotes a judicious use of antimicrobials and reduces the use of antimicrobials

Effect of intravenous dose escalation with alfaxalone and propofol on occurrence of apnoea in the dog

Spontaneous ventilation after induction of anaesthesia with intravenous alfaxalone or propofol was evaluated in a dose escalation study using 6 dogs. Each dog was dosed at 1×, 2×, 5×, 10× and 20× multiples of the labelled doses (2mg/kg for alfaxalone; 6.5mg/kg for propofol), until apnoea was observed. For each administration, the entire calculated dose was delivered over 1 min. All 6 dogs ventilated spontaneously after labelled (1×) doses of each drug but became apnoeic at 5× dose of propofol versus 20× dose of alfaxalone. For propofol at 2× and 5× doses, 4 and 0 dogs ventilated spontaneously respectively. For alfaxalone at 2×, 5× and 10× doses all 6, 4 and 1 dog ventilated spontaneously, respectively. The median dose which induced apnoea was higher for alfaxalone (5×) than for propofol (2×) (p=0.05). We concluded that induction of anaesthesia with propofol is more likely to induce apnoea than with alfaxalone

Survey of systemic antimicrobial prescribing for dogs by Victorian veterinarians

Objective: Investigate the current antimicrobial prescribing patterns of veterinarians in Victoria for dogs and compare these results to patterns described 20 years ago. Methods: A questionnaire was sent to 1380 veterinarians in Victoria. The first section collected demographic information of respondents. The second and third sections evaluated respondents’ approach to use of antimicrobial drugs for scenarios in dogs in which ‘clinical evidence suggests bacterial infection is the likely cause’ and where ‘it is unknown whether bacterial infection plays a role’. The final section evaluated respondents’ approach to use of antimicrobial drugs during dental extraction in a dog. Results: Of the 1380 veterinarians who were contacted, 259 responses were received (response rate 19%). Of these respondents, 95% (246/259) completed their veterinary degree at the University of Melbourne. The ratio of female to male respondents was 2.1 : 1 (171 : 82) and of urban to rural respondents was 1.9 : 1 (159 : 85). Drug selection for some scenarios was open to criticism. For example, to treat chronic prostatitis 16% (42/259) of respondents selected amoxicillin-clavulanate even though it has poor penetration of prostatic tissues. Some prescribing choices have changed since 1997; for example, for acute tracheobronchitis, 36% (73/204) of respondents indicated they would use antimicrobials, compared with 87% of respondents in 1997. For the treatment of idiopathic vestibular disease, only 5% (10/197) of respondents in the current study versus 45% (294/654) in the 1997 survey opted to use antimicrobials. Conclusion: Antimicrobial drug selection for treatment of dogs by registered veterinarians in Victoria was generally consistent with recent recommendations, although some details were widely variable

Accidental alfaxalone overdose in a mature cat undergoing anaesthesia for magnetic resonance imaging.

Case summary This case report describes the clinical signs and treatment of an alfaxalone 10 times overdose in a 12-year-old cat undergoing anaesthesia for MRI. The cat was discharged from hospital following a prolonged recovery including obtunded mentation and cardiorespiratory depression for several hours following cessation of anaesthesia. The cat received supportive therapy that included supplemental oxygen via a face mask, intravenous crystalloid fluids and active rewarming. The benefits of using alfaxalone for maintenance of anaesthesia, its pharmacokinetics and previously reported lethal doses are discussed. Strategies for reducing the incidence of medication errors are presented. Relevance and novel information An unintentional overdose of alfaxalone by continuous rate infusion has not been reported previously in a cat. Treatment is supportive and directed towards maintenance of the cardiorespiratory systems. Whenever possible, smart pumps that have been designed to reduce human error should be used to help prevent medication errors associated with continuous rate infusions

Chemical stability of morphine and methadone, and of methadone in combination with acepromazine, medetomidine or xylazine, during prolonged storage in syringes

Objective: To assess the chemical and physical stability of morphine and methadone stored in syringes for 12 months and of methadone when mixed with acepromazine, medetomidine or xylazine. Methods: A high-performance liquid chromatography (HPLC) technique was developed and validated for the analysis of morphine and methadone. Morphine and methadone were dispensed into syringes and stored at 25°C/60% relative humidity (RH) and 40°C/75% RH. Solutions containing mixtures of methadone combined with acepromazine, medetomidine or xylazine were stored in syringes at 25°C/60%RH. At initiation, after 1 week and then 1, 3, 6, 9 and 12 months, samples were analysed by HPLC for the quantification of the morphine or methadone. Measured concentrations were assessed as a function of storage time and temperature using linear regression statistics to calculate stability. Results: When stored at 40°C/75%RH as pre-dispensed syringes, severe physical and chemical changes were observed after the third month for both morphine and methadone. In contrast, at 25°C/60%RH both drugs remained chemically stable for 12 months, with concentration variations not exceeding a 5% change from initiation as stipulated in VICH stability guidelines. When in combination with acepromazine or xylazine, methadone also remained chemically stable, but the combination with medetomidine failed stability criteria prior to 6 months. Precipitation compromised the physical stability of methadone in all unsealed syringes prior to 9 months’ storage. Conclusion: Pre-dispensing morphine or methadone into unsealed syringes compromises the drugs’ physical stability. Mixing of methadone with other drugs can degrade its chemical stability

Population physiologically based modeling of pirlimycin milk concentrations in dairy cows

Predictions of drug residues in milk are critical in food protection and are a major consideration in the economics of treatment of mastitis in dairy cows. Nonlinear mixed-effects modeling (NLME) has been advocated as a suitable pharmaco-statistical method for the study of drug residues in milk. Recent developments in physiologically based pharmacokinetic (PBPK) modeling of intramammary drugs allow the combination of a mechanistic description of milk pharmacokinetics with NLME methods. The PBPK model was applied to NLME analysis of a data set consisting of milk drug concentrations from 78 healthy cows and 117 with clinical mastitis. Pirlimycin milk pharmacokinetics were adequately described by the model across the range of observed concentrations. Mastitis was characterized by increased variance in milk production volume. Udder residual volume was larger in cows with 1, or 2 or greater diseased mammary glands than in the healthy cows. Low-producing cows had a greater risk of prolonged milk residues. With the exclusion of the low-production cows, the model predicted that healthy cows required a milk discard time 12 h longer than that indicated by the label, and the diseased cows 36 h longer than indicated by the label. More pirlimycin was systemically absorbed in the gram-positive infected compared with the gram-negative infected or healthy cows, suggesting a greater risk of violative meat residues in gram-positive infected cows. Using NLME and PBPK models, we identified factors associated with changes in pirlimycin milk residues that may affect food safety. This model extends the verification of a simple physiologically based framework for the study of intramammary drugs

Study design synopsis: Designing and performing pharmacokinetic studies for systemically administered drugs in horses

The goal of this editorial is to discuss best practice design, execution and reporting of a pharmacokinetic (PK) study in horses. Our target readers are clinicians who plan to perform this type of research, in a field, clinic or research setting but we also hope that this article might help readers of such work to appraise the articles and understand the quality of the studies. Our emphasis will be on appropriate study design and analytical method, drug and drug formulation choice and route of administration, animal choice, sample collection, storage and shipping, and reporting, rather than the PK data analysis itself

Observations on the use of a pain numbing device for repetitive percutaneous sampling in sheep

Aims: To evaluate the success of a commercially available analgesic device (CoolSense; Coolsense Ltd, Tel Aviv, Israel) in ameliorating pain while sampling from subcutaneous tissue cages in sheep. Methods: The CoolSense device was used as part of a major parent study involving repetitive percutaneous sampling of subcutaneous tissue cages in seven sheep. Sampling was performed by passing a hypodermic needle through the skin and withdrawing fluid from the tissue cage. Each sheep had 10 tissue cages that were individually sampled 14 times over 74 h. The device was placed on the skin of the sampling site immediately before sampling cooling and numbing the skin. The reaction of the sheep was observed by the operators, flinching or jumping as the needle was passed through the skin was deemed to be a failure. We recorded the success or failure of the device for each needle stick. This was opportunistic data collection as part of a pharmacokinetic trial, therefore no controls were included. Results: A total of 1655 observations were recorded and then analysed using a generalised linear mixed model. Overall, 1380 of 1655 (83.4%) observations were recorded as successfully providing analgesia. Marked inter-occasion variability was noted with success ranging from 61.42% to 92.86% across sheep:period (approximately 140 observations each). As no controls were available, the effect of treatment could not be evaluated. Conclusions and clinical relevance: The CoolSense device is a viable option for veterinary research and clinical applications