Pharmacokinetic–pharmacodynamic modelling of the antinociceptive effect of a romifidine infusion in standing horses

ObjectiveTo evaluate the effect of a romifidine infusion on antinociception and sedation, and to investigate its relationship with plasma concentration.Study designProspective, experimental, nonrandomized trial.AnimalsA total of 10 healthy adult warmblood horses.MethodsRomifidine (loading dose: 0.08 mg kg^–1, infusion: 0.03 mg kg^–1 hour^–1) was administered intravenously over 120 minutes. Romifidine plasma concentrations were determined by capillary electrophoresis. Sedation quality and nociceptive thresholds were evaluated at regular time points before, during and after romifidine administration. The nociceptive withdrawal reflex was elicited by electrical stimulation at the thoracic limb using a dedicated threshold tracking algorithm and recorded by electromyography at the deltoid muscle. A pharmacokinetic–pharmacodynamic model was established and correlation between romifidine plasma concentration and main output variables tested.ResultsA two compartmental model best described the romifidine pharmacokinetic profile. The nociceptive thresholds increased compared with baseline in all horses from 10 to 146 minutes after romifidine administration (p < 0.001). Peak effect reached 5.7 ± 2.3 times the baseline threshold (mean ± standard deviation). The effect/concentration relationship followed a counter-clockwise hysteresis loop. The mean plasma concentration was weakly correlated to nociceptive thresholds (p < 0.0071, r = 0.392). The sedative effects were significant until 160 minutes but variable, not correlated to plasma concentration (p = 0.067), and weakly correlated to nociceptive thresholds (p < 0.0001, r = 0.33).Conclusions and clinical relevanceRomifidine elicited a marked antinociceptive effect. Romifidine-induced antinociception appeared with a delayed onset and lasted longer than sedation after discontinuing its administration.     

Does multiple oral vaccination of wild boar against classical swine fever (CSF) have a positive influence on the immunity?

We studied the efficacy of multiple vaccinations of wild boar against classical swine fever (CSF) using a C-strain vaccine. The study consisted of two experiments. In the first experiment, 7 to 8 months old animals were vaccinated either three or four times at an interval of 7 days or twice at an interval of 14 or 28 days. In the second experiment, the efficacy of oral immunisation in young boars (3 months old) was examined after fivefold vaccination at intervals of 14 or 28 days. Independently of the immunisation scheme all wild boar developed neutralising antibodies. An evaluation of the antibody titres 28 days after the initial vaccine application showed that single vaccination and triple immunisation at an interval of 7 days induced the highest antibody titres (X > or = 1/80). In multiple vaccinated young boars (vaccinated at intervals of 14 or 28 days) the third vaccination led to a slight reduction or to an only moderate increase of the antibody titre. In a challenge study after the fifth vaccination all wild boar were protected (no viraemia, no virus excretion, no post-mortem virus detection in organs). This was confirmed by the fact that sentinel animals were not affected. Although other immunisation schemes also were effective, booster vaccination at an interval of 28 days is recommended as basic procedure for eradication of CSF in wild boar. Triple vaccination might also be used at the beginning of the control measures.     

A preliminary study on the effect of wounding on transforming growth factor-β1 and cartilage oligomeric matrix protein concentrations in the skin of horses

Objective: To evaluate whether wound type or site influence the production of cartilage oligomeric matrix protein (COMP) and transforming growth factor β1 (TGF‐β1), and determine if there is a correlation between TGF‐β1and COMP during healing. Study Design: Experimental. Animals: Standardbred horses (n=6), 4–8 years old. Methods: Six, standardized, full‐thickness skin wounds (open, straight, and elliptical) were surgically created on the neck (n=3) and metacarpus (3) on each horse. Wounds were randomly allocated to site and side. Tissue samples were collected before creating wounds and on days 7, 14, and 42. COMP concentration (μg/g dry weight of tissue) was determined using a standard competitive ELISA and TGF‐β1 (ng/g dry weight of tissue) was determined using a commercially available sandwich ELISA. Results: COMP concentrations were higher in intact skin on the neck compared with the metacarpus (P=.02). There was no difference in COMP and TGF‐β1 concentrations between the different wound types or sites during healing. There was no correlation between TGF‐β1 and COMP during healing. Conclusions: Within the limitations of the study design, production of COMP during healing of skin wounds does not appear to be influenced by wound type or anatomic site, nor does it appear to be correlated with TGF‐β1 concentrations.     

Bacterial culture of septic synovial structures of horses: Does a positive bacterial culture influence prognosis?

Reasons for performing study: The influence of synovial fluid culture on short‐ and long‐term prognosis of cases with septic synovitis requires study. Hypotheses: Horses with a positive bacterial culture from septic synovial fluid are less likely to survive or return to successful athletic function than those with a negative bacterial culture from septic synovial fluid. Methods: Records of mature horses presented to 2 equine referral hospitals for investigation of suspected septic synovitis were examined. Horses (n = 206) were included in the study if synovial fluid was submitted for full laboratory examination, including bacterial culture. A diagnosis of septic synovitis was based on a nucleated cell count >30 × 10⁹ cells/l or >90% neutrophils and other clinical, cytological and bacteriological parameters. Long‐term follow‐up was obtained by telephone questionnaire. Univariate analysis, using the Fisher's exact test, was used for all outcomes. Results: Fourteen (20.9%) of 67 horses with a positive bacterial culture from synovial fluid were subjected to euthanasia because of persistent synovial sepsis compared to 2 (1.44%) of 139 with negative bacterial cultures (P<0.001). Overall survival and successful long‐term return to function in horses with a positive bacterial culture was 50% (24/48 horses) compared to 70.5% (74/105) in culture negative horses (P = 0.01). In horses that survived to be discharged, successful long‐term return to function was not significantly different between culture positive and culture negative groups. Growth of Staphylococcus aureus from synovial fluid did not affect short‐term survival to discharge from the hospital compared to other positive bacterial culture; however, successful long‐term return to function was only 30.4% (4/13) in horses from which S. aureus was cultured compared to 73.9% (17/23) of horses in which other bacteria were cultured (P = 0.015). Conclusions and potential clinical relevance: Horses with a positive bacterial culture from a septic synovitis have a poorer prognosis for survival to discharge from hospital and overall long‐term return to function than horses that yielded no bacterial growth. When S. aureus was cultured, the long‐term prognosis was poorer.     

Is there a lasting effect of functional claw-trimming on claw conditions?

The influence of regular claw-trimming on the occurrence and prevalence of claw disorders was examined on a total of 164 dairy cows (Simmental, Red Friesian, Holstein Friesian). Ten dairy farms in the Austrian province of Salzburg were used for this study. Three examinations of the claws were carried out with an interval of six months in between to find out claw disorders. The results were recorded according to a claw scoring system. The claw scores were in the range of other studies using the same scoring system. The median of the claw scores at the beginning of the study was 27 in the tied stall group compared with 37 in the loose housing group, remaining at that level in the first group and falling to 25 in the second group. All in all, the positive effect of regular claw trimming was more pronounced in the loose housing group than in the tethered housing group.     

Post anaesthetic colic in horses: a preventable complication?

REASONS FOR PERFORMING STUDY: There is little information on the prevalence of, and risk factors associated with, post anaesthetic colic (PAC) in horses undergoing nonabdominal operations. OBJECTIVES: To undertake the first prospective study of prevalence of PAC and identify risk factors in its development in nonabdominal procedures. METHODS: A multicentre prospective case-control study was conducted, on every horse undergoing anaesthesia for a nonabdominal procedure between April 2004 and June 2005. Colic cases were defined as any horse with recognised signs of abdominal pain within 72 h of general anaesthesia that could not be attributed to any concurrent disease. Five control horses per case were selected randomly from the study population at all hospitals. Multivariable logistic regression analysis was used to examine the relationship between predictor variables and the risk of developing PAC. RESULTS: The estimated mean prevalence of PAC in the study population was 5.2% (95% CI, 2.8, 8.0). However, the prevalence of colic varied between each centre. The most commonly diagnosed cause of colic was impaction. Multivariable analyses showed that the centre involved and the type of surgery performed were associated with an increased risk of PAC. Preoperative food deprivation and the use of opioid drugs were confounding factors. CONCLUSIONS: Prevalence of PAC varied significantly between the 4 hospitals studied; there may be hospital-related covariates that account for this. The type of surgery performed influenced the risk of PAC. POTENTIAL RELEVANCE: Identifying the risk factors for PAC is a prerequisite for its prevention. This study indicates horses at increased risk of PAC that might benefit from a more critical evaluation of post anaesthetic gastrointestinal function and/or the provision of preventative measures. Further investigation is required to explain the variation in prevalence of PAC between centres.     

Canine brain tumours: a model for the human disease?

Canine brain tumours are becoming established as naturally occurring models of disease to advance diagnostic and therapeutic understanding successfully. The size and structure of the dog's brain, histopathology and molecular characteristics of canine brain tumours, as well as the presence of an intact immune system, all support the potential success of this model. The limited success of current therapeutic regimens such as surgery and radiation for dogs with intracranial tumours means that there can be tremendous mutual benefit from collaboration with our human counterparts resulting in the development of new treatments. The similarities and differences between the canine and human diseases are described in this article, emphasizing both the importance and limitations of canines in brain tumour research. Recent clinical veterinary therapeutic trials are also described to demonstrate the areas of research in which canines have already been utilized and to highlight the important potential benefits of translational research to companion dogs.     

Neurological trypanosomiasis in quinapyramine sulfate-treated horses—a breach of the blood–brain barrier?

Trypanosoma evansi infection typically produces wasting disease, but it can also develop into a neurological or meningoencephalitis form in equids. Trypanosomiasis in horses was treated with quinapyramine sulfate, and all the 14 infected animals were recovered clinically. After clinical recovery, four animals developed a neurological form of the disease at various intervals. Two of these animals treated with diminazene aceturate recovered temporarily. Repeated attempts failed to find the parasite in the blood or the cerebrospinal fluid (CSF), but all of the animals were positive in enzyme-linked immunosorbent assay. The calculation of the antibody index (AI) in the serum and the CSF and polymerase chain reaction (PCR) analysis of the CSF and brain tissue were carried out to confirm the neuro-infection. We found PCR and AI analyses of the CSF to be useful tools in the diagnosis of the neurological form of trypanosomiasis when the organism cannot be found in the blood or CSF. The increased albumin quotient is indicative of barrier leakage due to neuroinflammation. The biochemical changes in the CSF due to nervous system trypanosomiasis include increases in the albumin quotient, total protein, and urea nitrogen. It seems to be the first report on relapse of the nervous form of trypanosomiasis in equids even after quinapyramine treatment in endemic areas.