Diagnostic value of blood variables following attenuation of congenital extrahepatic portosystemic shunt in dogs.

BACKGROUND: The aims of this study were to determine if extrahepatic portosystemic shunt (EHPSS) postoperative closure could be predicted based on preoperative blood analyses and to determine the accuracy of blood variables to evaluate persistence of portosystemic shunting postoperatively (multiple acquired portosystemic shunts (MAPSS) or persistent EHPSS). METHODS: Retrospectively, 62 dogs treated surgically for congenital EHPSS that underwent postoperative trans-splenic portal scintigraphy or CT angiography three to six months postoperatively were included. RESULTS: None of the studied preoperative blood variables could unambiguously predict surgical outcome. Elevated postoperative fasting venous ammonia (FA) concentration always indicated surgical failure (persistent shunting or MAPSS), but normal FA did not provide any information on the postoperative shunting status. Paired serum bile acids (SBA) were not reliable enough to confirm or exclude postoperative shunting. In the presence of low normal postoperative FA levels, elevated preprandial SBA was more likely in dogs with persistent shunting (sensitivity of 0.79, specificity of 0.83), whereas postprandial SBA below reference limit was more often observed in case of surgical success (sensitivity of 0.93, specificity of 0.67). CONCLUSION: Blood variables, and more specifically the combination of FA and SBA, are not a valuable alternative to advanced medical imaging to reliably assess the surgical outcome after EHPSS surgery.

Kinetic analysis of [18F] altanserin bolus injection in the canine brain using PET imaging.

BACKGROUND: Currently, [18F] altanserin is the most frequently used PET-radioligand for serotonin2A (5-HT2A) receptor imaging in the human brain but has never been validated in dogs. In vivo imaging of this receptor in the canine brain could improve diagnosis and therapy of several behavioural disorders in dogs. Furthermore, since dogs are considered as a valuable animal model for human psychiatric disorders, the ability to image this receptor in dogs could help to increase our understanding of the pathophysiology of these diseases. Therefore, five healthy laboratory beagles underwent a 90-min dynamic PET scan with arterial blood sampling after [18F] altanserin bolus injection. Compartmental modelling using metabolite corrected arterial input functions was compared with reference tissue modelling with the cerebellum as reference region. RESULTS: The distribution of [18F] altanserin in the canine brain corresponded well to the distribution of 5-HT2A receptors in human and rodent studies. The kinetics could be best described by a 2-Tissue compartment (2-TC) model. All reference tissue models were highly correlated with the 2-TC model, indicating compartmental modelling can be replaced by reference tissue models to avoid arterial blood sampling. CONCLUSIONS: This study demonstrates that [18F] altanserin PET is a reliable tool to visualize and quantify the 5-HT2A receptor in the canine brain.

Alfaxalone total intravenous anaesthesia in dogs: pharmacokinetics, cardiovascular data and recovery characteristics.

OBJECTIVE: To evaluate the cardiovascular effects, pharmacokinetic (PK) data and recovery characteristics of an alfaxalone constant rate infusion (CRI) of different duration in dogs at manufacturer's recommended dose rate. STUDY DESIGN: Experimental, prospective, randomized, crossover study. ANIMALS: Six intact female Beagles. METHODS: Following an intravenous alfaxalone bolus (3 mg kg-1), anaesthesia was maintained using an alfaxalone CRI at 0.15 mg kg-1 minute-1 for 90 (short CRI) or 180 minutes (long CRI). Venous blood samples were collected to determine the PK profile. Cardiovascular variables and recovery characteristics were evaluated. Recovery was scored on a scale ranging from 0, excellent to 4, bad. A mixed-model statistical approach was used to compare the cardiovascular parameters (global α = 0.05). An analysis of variance was performed to compare PK parameters and recovery times between treatments. RESULTS: No significant difference was noted between protocols for any PK parameter. Volume of distribution at steady state (935.74 ± 170.25 versus 1119.15 ± 190.65 mL kg-1), elimination half-life (12 ± 2 versus 13 ± 3 minutes), clearance from the central compartment (26.02 ± 4.41 versus 27.74 ± 5.65 mL kg-1 minute-1) and intercompartmental clearance (8.47 ± 4.06 versus 12.58 ± 7.03 mL kg-1 minute-1) were comparable for short CRI and long CRI. Cardiovascular variables remained within physiological limits. Mechanical ventilation was necessary (short CRI: n = 1, long CRI: n = 4). The manufacturer's recommended dose rate resulted in a light plane of anaesthesia. No significant differences in recovery times and scores were observed between treatments. The quality of recovery was scored as very poor with both protocols. CONCLUSIONS AND CLINICAL RELEVANCE: PK data were similar between long and short infusions of alfaxalone at the manufacturer's recommended dose, with acceptable cardiovascular conditions. Nevertheless, both protocols resulted in a superficial plane of general anaesthesia with poor recovery characteristics.

Effect of premedication on dose requirement, cardiovascular effects and recovery quality of alfaxalone total intravenous anaesthesia in dogs.

OBJECTIVE: To investigate alfaxalone total intravenous anaesthesia (TIVA) following premedication with methadone combined with acepromazine (ACP) or dexmedetomidine in bitches undergoing ovariohysterectomy. STUDY DESIGN: Prospective, blinded, randomized, experimental study. ANIMALS: A group of 12 female Beagles. METHODS: Dogs were premedicated intravenously with methadone (0.2 mg kg-1) combined with ACP (20 µg kg-1, group AM) or dexmedetomidine (5 µg kg-1, group DM). Anaesthesia was induced with alfaxalone (2 mg kg-1). Anaesthetic maintenance was obtained with an alfaxalone variable rate infusion (VRI) started at 0.15 mg kg-1 minute-1 and adjusted every 5 minutes based on clinical assessment. Mechanical ventilation was initiated when necessary to maintain normocapnia. Anaesthetic monitoring included electrocardiogram, heart rate (HR), invasive diastolic (DAP), systolic (SAP) and mean arterial blood pressure, arterial haemoglobin oxygen saturation, respiratory variables and oesophageal temperature. Data were recorded every 5 minutes. A mixed model statistical approach was used to compare cardiovascular variables within and between groups (α = 0.05). A Wilcoxon rank-sum test was used to compare body temperature, VRI alfaxalone rate, administered rescue analgesia, sedation, induction, intubation, recovery scores and recovery times between treatments. RESULTS: Overall HR, SAP and DAP differed between groups (p = 0.001, 0.016, 0.019, respectively). The mean VRI dose rate of alfaxalone differed between groups DM [0.13 (0.11-0.14) mg kg-1 minute-1] and AM [0.18 (0.13-0.19) mg kg-1 minute-1; p = 0.030]. Rescue analgesia was administered more in group AM (p = 0.019). No significant difference in recovery times and scores was observed between protocols. CONCLUSIONS AND CLINICAL RELEVANCE: Alfaxalone TIVA following dexmedetomidine/methadone premedication produced a more stable plane of anaesthesia to perform ovariohysterectomy than ACP/methadone. A dose reduction of alfaxalone of 27.7% was obtained in group DM compared with group AM. Recovery quality and recovery times were comparable between both groups.

PET quantification of [18F]MPPF in the canine brain using blood input and reference tissue modelling.

Numerous studies have shown that the serotonin1A (5-HT1A) receptor is implicated in the pathophysiology and treatment of several psychiatric and neurological disorders. Furthermore, functional imaging studies in a variety of species have demonstrated that 4-(2´-Methoxyphenyl)-1-[2´-(N-2´´-pyridinyl)-p- [18F]fluorobenzamidoethylpiperazine ([18F]MPPF) is a valid and useful PET tracer to visualize the 5HT1A receptor. However, to our knowledge, [18F]MPPF has never been demonstrated in the canine brain. The ability to image the 5HT1A receptor with PET in dogs could improve diagnosis and therapy in both canine and human behavioural and neuropsychiatric disorders. To examine the potential use of [18F]MPPF in dogs, five healthy adult laboratory beagles underwent a 60-minutes dynamic PET scan with [18F]MPPF while arterial blood samples were taken. For each region of interest, total distribution volume (VT) and corresponding binding potential (BPND) were calculated using the 1-tissue compartment model (1-TC), 2-Tissue compartment model (2-TC) and Logan plot. The preferred model was chosen based on the goodness-of-fit, calculated with the Akaike information criterium (AIC). Subsequently, the BPND values of the preferred compartment model were compared with the estimated BPND values using three reference tissue models (RTMs): the 2-step simplified reference tissue model (SRTM2), the 2-parameter multilinear reference tissue model (MRTM2) and the Logan reference tissue model. According to the lower AIC values of the 2-TC model compared to the 1-TC in all ROIs, the 2-TC model showed a better fit. Calculating BPND using reference tissue modelling demonstrated high correlation with the BPND obtained by metabolite corrected plasma input 2-TC. This first-in-dog study indicates the results of a bolus injection with [18F]MPPF in dogs are consistent with the observations presented in the literature for other animal species and humans. Furthermore, for future experiments, compartmental modelling using invasive blood sampling could be replaced by RTMs, using the cerebellum as reference region.

Comparison of Three Methods to Quantify Laxity in the Canine Hip Joint.

OBJECTIVES: Comparison of PennHIP and a novel method to diagnose hip laxity, called the Vezzoni modified Badertscher distension device technique. METHODS: In a total of 10 dogs, it was first assessed whether the distraction index (DI) from the PennHIP evaluation center could be reproduced by two individual observers. In the next two steps, the DI measurements made by the individual observers and the PennHIP evaluation center were compared with the laxity index (LI) measured on the Vezzoni modified Badertscher distension device view. Finally, the interobserver agreement of the DI, LI and Norberg angle was assessed and compared with classification criteria. RESULTS: The results were similar for the first three comparisons: there was no evidence for bias, the relation between DI and LI was linear and the variability was small. A comparison of the interobserver agreement showed that the measurement variability for the NA was substantial, while the reproducibility for the DI and LI was equal. CLINICAL SIGNIFICANCE: While the standard ventrodorsal hip extended radiograph is most commonly used for diagnosis and screening of canine hip dysplasia, it lacks sensitivity to diagnose laxity. To improve the identification of hip joint laxity, distraction-based radiographic techniques are helpful. The Vezzoni modified Badertscher distension device technique allows for a reliable in-house evaluation of canine hip joint laxity.

Cardiovascular effects, induction and recovery characteristics and alfaxalone dose assessment in alfaxalone versus alfaxalone-fentanyl total intravenous anaesthesia in dogs.

OBJECTIVE: To compare cardiovascular effects and anaesthetic quality of alfaxalone alone or in combination with a fentanyl constant rate infusion (CRI) when used for total intravenous anaesthesia (TIVA) in dogs. STUDY DESIGN: Prospective, blinded, randomized, experimental study. ANIMALS: A group of 12 intact female dogs. METHODS: Following intramuscular dexmedetomidine (10 µg kg-1) and methadone (0.1 mg kg-1) administration, anaesthesia was induced intravenously with alfaxalone (2 mg kg-1) (group AP) or alfaxalone (2 mg kg-1) preceded by fentanyl (2 µg kg-1) (group AF). Anaesthetic maintenance was obtained with an alfaxalone variable rate infusion (VRI) started at 0.15 mg kg-1 minute-1 (group AP) or an alfaxalone VRI (same starting rate) combined with a CRI of fentanyl (10 µg kg-1 hour-1) (group AF). The alfaxalone VRI was adjusted every 5 minutes, based on clinical assessment. Cardiovascular parameters (recorded every 5 minutes) and recovery characteristics (using a numerical rating scale) were compared between groups. A mixed model statistical approach was used to compare the mean VRI alfaxalone dose and cardiovascular parameters between groups; recovery scores were analysed using the Wilcoxon rank-sum test (α = 0.05). RESULTS: The mean CRI alfaxalone dose for anaesthetic maintenance differed significantly between treatments [0.16 ± 0.01 mg kg-1 minute-1 (group AP) versus 0.13 ± 0.01 mg kg-1 minute-1 (group AF)]. Overall heart rate, systolic, mean and diastolic arterial pressures were lower in group AF than in group AP (p < 0.0001, p = 0.0058, p < 0.0001 and p < 0.0001, respectively. Recovery quality scores did not differ significantly and were poor in both groups. CONCLUSIONS AND CLINICAL RELEVANCE: In combination with a fentanyl CRI, an alfaxalone TIVA provides a cardiovascular stable anaesthesia in dogs. The addition of fentanyl results in a significant dose reduction. The quality of anaesthetic recovery remains poor.

Negative pressure wound therapy using polyvinyl alcohol foam to bolster full-thickness mesh skin grafts in dogs.

OBJECTIVE: To report the use of negative pressure wound therapy (NPWT) with polyvinyl alcohol (PVA) foam to bolster full-thickness mesh skin grafts in dogs. STUDY DESIGN: Retrospective case series. ANIMALS: Client-owned dogs (n = 8). MATERIAL AND METHODS: Full-thickness mesh skin graft was directly covered with PVA foam. NPWT was maintained for 5 days (in 1 or 2 cycles). Grafts were evaluated on days 2, 5, 10, 15, and 30 for graft appearance and graft take, granulation tissue formation, and complications. RESULTS: Firm attachment of the graft to the recipient bed was accomplished in 7 dogs with granulation tissue quickly filling the mesh holes, and graft take considered excellent. One dog had bandage complications after cessation of the NPWT, causing partial graft loss. The PVA foam did not adhere to the graft or damage the surrounding skin. CONCLUSION: The application of NPWT with a PVA foam after full-thickness mesh skin grafting in dogs provides an effective method for securing skin grafts, with good graft acceptance. PVA foam can be used as a primary dressing for skin grafts, obviating the need for other interposing materials to protect the graft and the surrounding skin.

Regional cerebral blood flow assessed by single photon emission computed tomography (SPECT) in dogs with congenital portosystemic shunt and hepatic encephalopathy.

Regional cerebral blood flow (rCBF) in eight dogs with congenital portosystemic shunt (PSS) and hepatic encephalopathy (HE) was compared with rCBF in eight healthy control dogs using single photon emission computed tomography (SPECT) with a 99mtechnetium-hexamethylpropylene amine oxime (99mTc-HMPAO) tracer. SPECT scans were abnormal in all PSS dogs. Compared to the control group, rCBF in PSS dogs was significantly decreased in the temporal lobes and increased in the subcortical (thalamic and striatal) area. Brain perfusion imaging alterations observed in the dogs with PSS and HE are similar to those in human patients with HE. These findings suggest that dogs with HE and PSS have altered perfusion of mainly the subcortical and the temporal regions of the brain.

Evaluation of Feline Renal Perfusion with Contrast-Enhanced Ultrasonography and Scintigraphy.

Contrast-enhanced ultrasound (CEUS) is an emerging technique to evaluate tissue perfusion. Promising results have been obtained in the evaluation of renal perfusion in health and disease, both in human and veterinary medicine. Renal scintigraphy using 99mTc-Mercaptoacetyltriglycine (MAG3) is another non-invasive technique that can be used to evaluate renal perfusion. However, no data are available on the ability of CEUS or 99mTc- MAG3 scintigraphy to detect small changes in renal perfusion in cats. Therefore, both techniques were applied in a normal feline population to evaluate detection possibilities of perfusion changes by angiotensin II (AT II). Contrast-enhanced ultrasound using a bolus injection of commercially available contrast agent and renal scintigraphy using 99mTc-MAG3 were performed in 11 healthy cats after infusion of 0,9% NaCl (control) and AT II. Angiotensin II induced changes were noticed on several CEUS parameters. Mean peak enhancement, wash-in perfusion index and wash-out rate for the entire kidney decreased significantly after AT II infusion. Moreover, a tendency towards a lower wash-in area-under-the curve was present. Renal scintigraphy could not detect perfusion changes induced by AT II. This study shows that CEUS is able to detect changes in feline renal perfusion induced by AT II infusion.

Clinical efficacy and cardiorespiratory effects of intramuscular administration of alfaxalone alone or in combination with dexmedetomidine in cats.

OBJECTIVE: To investigate the sedative, anaesthetic and cardiorespiratory effects of intramuscular (IM) administration of alfaxalone alone or in combination with dexmedetomidine in cats. STUDY DESIGN: Blinded, randomized crossover study with a washout period of 15 days. ANIMALS: Seven adult cats, weighing 3.5 ± 0.7 kg. METHODS: Cats were assigned randomly to each of three treatments: A5 (alfaxalone 5 mg kg(-1) ), D20 A5 (dexmedetomidine 20 µg kg(-1) and alfaxalone 5 mg kg(-1) ) and D40 A5 (dexmedetomidine 40 µg kg(-1) and alfaxalone 5 mg kg(-1) ). Drugs were administered IM into the epaxial muscles. Sedation or anaesthesia scores were evaluated by a modified numerical rating scale. Times to extubation, head-lift, sternal recumbency and standing were recorded. Heart and respiratory rates, systolic arterial pressure, arterial oxygen saturation of haemoglobin, end-tidal carbon dioxide tension and rectal temperature were measured at 5, 10, 15, 20, 30, 45, 60, 90, 120 and 150 minutes after drug administration. Adverse events were recorded. Data were analysed by one-way anova with Tukey's post-hoc test for parametric values and, for non-normally distributed parameters, a Kruskal-Wallis test and Mann-Whitney U-test for two independent samples (p < 0.05). RESULTS: Sedation scores were significantly different among the treatments. Cats in A5 were deeply sedated, whereas cats administered dexmedetomidine were anaesthetized. The onset of action and the duration of anaesthesia were related to the dose of dexmedetomidine. Cardiorespiratory parameters remained stable in the A5 group. Lower heart rates, higher systolic blood pressures and occasional low pulse oximetry readings were observed in the dexmedetomidine groups. A limited number of adverse events (hyperkinesia, emesis) occurred during recovery. CONCLUSIONS AND CLINICAL RELEVANCE: Alfaxalone administered IM induced sedation in cats. The addition of dexmedetomidine to alfaxalone induced general anaesthesia with a mild decrease in the heart rate and arterial oxygen saturation of haemoglobin.

In vivo quantification of the [(11)C]DASB binding in the normal canine brain using positron emission tomography.

BACKGROUND: [(11)C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile ([(11)C]DASB) is currently the mostly used radiotracer for positron emission tomography (PET) quantitative studies of the serotonin transporter (SERT) in the human brain but has never been validated in dogs. The first objective was therefore to evaluate normal [(11)C]DASB distribution in different brain regions of healthy dogs using PET. The second objective was to provide less invasive and more convenient alternative methods to the arterial sampling-based kinetic analysis. RESULTS: A dynamic acquisition of the brain was performed during 90 min. The PET images were coregistered with the magnetic resonance images taken prior to the study in order to manually drawn 20 regions of interest (ROIs). The highest radioactivity concentration of [(11)C]DASB was observed in the hypothalamus, raphe nuclei and thalamus and lowest levels in the parietal cortex, occipital cortex and cerebellum. The regional radioactivity in those 20 ROIs was quantified using the multilinear reference tissue model 2 (MRTM2) and a semi-quantitative method. The values showed least variability between 40 and 60 min and this time interval was set as the optimal time interval for [(11)C]DASB quantification in the canine brain. The correlation (R(2)) between the MRTM2 and the semi-quantitative method using the data between 40 and 60 min was 99.3% (two-tailed p-value < 0.01). CONCLUSIONS: The reference tissue models and semi-quantitative method provide a more convenient alternative to invasive arterial sampling models in the evaluation of the SERT of the normal canine brain. The optimal time interval for static scanning is set at 40 to 60 min after tracer injection.

An heuristic filtering tool to identify phenotype-associated genetic variants applied to human intellectual disability and canine coat colors.

BACKGROUND: Identification of one or several disease causing variant(s) from the large collection of variants present in an individual is often achieved by the sequential use of heuristic filters. The recent development of whole exome sequencing enrichment designs for several non-model species created the need for a species-independent, fast and versatile analysis tool, capable of tackling a wide variety of standard and more complex inheritance models. With this aim, we developed "Mendelian", an R-package that can be used for heuristic variant filtering. RESULTS: The R-package Mendelian offers fast and convenient filters to analyze putative variants for both recessive and dominant models of inheritance, with variable degrees of penetrance and detectance. Analysis of trios is supported. Filtering against variant databases and annotation of variants is also included. This package is not species specific and supports parallel computation. We validated this package by reanalyzing data from a whole exome sequencing experiment on intellectual disability in humans. In a second example, we identified the mutations responsible for coat color in the dog. This is the first example of whole exome sequencing without prior mapping in the dog. CONCLUSION: We developed an R-package that enables the identification of disease-causing variants from the long list of variants called in sequencing experiments. The software and a detailed manual are available at https://github.com/BartBroeckx/Mendelian.

Improved canine exome designs, featuring ncRNAs and increased coverage of protein coding genes.

By limiting sequencing to those sequences transcribed as mRNA, whole exome sequencing is a cost-efficient technique often used in disease-association studies. We developed two target enrichment designs based on the recently released annotation of the canine genome: the exome-plus design and the exome-CDS design. The exome-plus design combines the exons of the CanFam 3.1 Ensembl annotation, more recently discovered protein-coding exons and a variety of non-coding RNA regions (microRNAs, long non-coding RNAs and antisense transcripts), leading to a total size of ≈ 152 Mb. The exome-CDS was designed as a subset of the exome-plus by omitting all 3' and 5' untranslated regions. This reduced the size of the exome-CDS to ≈ 71 Mb. To test the capturing performance, four exome-plus captures were sequenced on a NextSeq 500 with each capture containing four pre-capture pooled, barcoded samples. At an average sequencing depth of 68.3x, 80% of the regions and well over 90% of the targeted base pairs were completely covered at least 5 times with high reproducibility. Based on the performance of the exome-plus, we estimated the performance of the exome-CDS. Overall, these designs provide flexible solutions for a variety of research questions and are likely to be reliable tools in disease studies.

Prepubertal gonadectomy in cats: different injectable anaesthetic combinations and comparison with gonadectomy at traditional age.

Anaesthetic and analgesic effects of three different injectable anaesthetic combinations for prepubertal gonadectomy (PPG) in cats were studied. One anaesthetic protocol was compared with a similar one for gonadectomy at traditional age (TAG). Kittens were randomly assigned to PPG or TAG. For PPG, three different protocols were compared: (1) intramuscular (IM) administration of 60 µg/kg dexmedetomidine plus 20 µg/kg buprenorphine followed by an IM injection of the anaesthetic agent (20 mg/kg ketamine) (DB-IM protocol); (2) oral transmucosal (OTM) administration of 80 µg/kg dexmedetomidine plus 20 µg/kg buprenorphine followed by an IM injection of 20 mg/kg ketamine combined with 20 µg/kg dexmedetomidine (DB-OTM protocol); (3) IM injection of a 40 µg/kg medetomidine-20 µg/kg buprenorphine-20 mg/kg ketamine combination (MBK-IM protocol). For TAG, a DB-IM protocol was used, but with different doses for dexmedetomidine (40 µg/kg) and ketamine (5 mg/kg). All cats (PPG and TAG) received a non-steroidal anti-inflammatory before surgery. Anaesthetic and analgesic effects were assessed pre- and postoperatively (until 6 h). Cumulative logit, linear and logistic regression models were used for statistical analysis. Compared with the DB-OTM protocol, the DB-IM and MBK-IM protocols provided better anaesthesia with fewer adverse effects in PPG cats. Postoperative pain was not significantly different between anaesthetic protocols. PPG and TAG cats anaesthetised with the two DB-IM protocols differed significantly only for sedation and pain scores, but sedation and pain scores were generally low. Although there were no anaesthesia-related mortalities in the present study and all anaesthetic protocols for PPG in cats provided a surgical plane of anaesthesia and analgesia up to 6 h postoperatively, our findings were in favour of the intramuscular (DB-IM and MBK-IM) protocols.

TTA Rapid: Description of the Technique and Short Term Clinical Trial Results of the First 50 Cases.

OBJECTIVE: To (1) describe a modified technique for tibial tuberosity advancement (TTA) in dogs with cranial cruciate ligament (CCL) rupture and (2) report short term outcome and complications. STUDY DESIGN: Prospective clinical study. ANIMALS: Dogs with unilateral CCL rupture (n = 50). METHODS: TTA was performed with a novel implant to achieve advancement of the tibial crest. The technical protocol, specific implants and instrumentation, and the short term outcome are described. RESULTS: Various breeds (mean ± SD weight, 31.9 ± 13.3 kg) were included. Mean age at treatment was 64 ± 30.6 months. Minor complications occurred in 30% and major complications in 4% of the cases. Forty-eight (96%) dogs had a good to excellent outcome 3 months after surgery. CONCLUSION: The modified technique is a viable alternative to other osteotomy techniques.

Sedative and antinociceptive effects of dexmedetomidine and buprenorphine after oral transmucosal or intramuscular administration in cats.

OBJECTIVE: To compare sedation and antinociception after oral transmucosal (OTM) and intramuscular (IM) administration of a dexmedetomidine-buprenorphine combination in healthy adult cats. STUDY DESIGN: Randomized, 'blinded' crossover study, with 1 month washout between treatments. ANIMALS: Six healthy neutered female cats, weighing 5.3-7.5 kg. METHODS: A combination of dexmedetomidine (40 µg kg(-1) ) and buprenorphine (20 µg kg(-1) ) was administered by either the OTM (buccal cavity) or IM (quadriceps muscle) route. Sedation was measured using a numerical rating scale, at baseline and at various time points until 6 hours after treatment. At the same time points, analgesia was scored using a dynamic and interactive visual analogue scale, based on the response to an ear pinch, and by the cat's response to a mechanical stimulus exerted by a pressure rate onset device. Physiological and adverse effects were recorded, and oral pH measured. Signed rank tests were performed, with significance set at p < 0.05. Data are presented as median and range. RESULTS: There were no differences in sedation or antinociception scores between OTM and IM dosing at any of the time points. Nociceptive thresholds increased after both treatments but without significant difference between groups. Buccal pH remained between 8 and 8.5. Salivation was noted after OTM administration (n = 2) and vomiting after both OTM (n = 4), and IM (n = 3) dosing. CONCLUSIONS AND CLINICAL RELEVANCE: In healthy adult cats, OTM administration of dexmedetomidine and buprenorphine resulted in comparable levels of sedation and antinociception to IM dosing. The OTM administration may offer an alternative route to administer this sedative-analgesic combination in cats.

The prevalence of nine genetic disorders in a dog population from Belgium, the Netherlands and Germany.

The objective of this study was to screen a dog population from Belgium, the Netherlands and Germany for the presence of mutant alleles associated with hip dysplasia (HD), degenerative myelopathy (DM), exercise-induced collapse (EIC), neuronal ceroid lipofuscinosis 4A (NCL), centronuclear myopathy (HMLR), mucopolysaccharidosis VII (MPS VII), myotonia congenita (MG), gangliosidosis (GM1) and muscular dystrophy (Duchenne type) (GRMD). Blood samples (K3EDTA) were collected for genotyping with Kompetitive Allele Specific PCR (n = 476). Allele and genotype frequencies were calculated in those breeds with at least 12 samples (n = 8). Hardy-Weinberg equilibrium was tested. Genetic variation was identified for 4 out of 9 disorders: mutant alleles were found in 49, 15, 3 and 2 breeds for HD, DM, EIC and NCL respectively. Additionally, mutant alleles were identified in crossbreeds for both HD and EIC. For HD, DM, EIC and NCL mutant alleles were newly discovered in 43, 13, 2 and 1 breed(s), respectively. In 9, 2 and 1 breed(s) for DM, EIC and NCL respectively, the mutant allele was detected, but the respective disorder has not been reported in those breeds. For 5 disorders (HMLR, MPS VII, MG, GM1, GRMD), the mutant allele could not be identified in our population. For the other 4 disorders (HD, DM, EIC, NCL), prevalence of associated mutant alleles seems strongly breed dependent. Surprisingly, mutant alleles were found in many breeds where the disorder has not been reported to date.