'Low' faecal immunochemical test (FIT) colorectal cancer: a 4-year comparison of the Nottingham '4F' protocol with FIT10 in symptomatic patients.

AIM: The aim of this work was to evaluate colorectal cancer (CRC) outcomes after 'low' (sub-threshold) faecal immunochemical test (FIT) results in symptomatic patients tested in primary care. METHOD: This work comprised a retrospective audit of 35 289 patients with FIT results who had consulted their general practitioner with lower gastrointestinal symptoms and had subsequent CRC diagnoses. The Rapid Colorectal Cancer Diagnosis pathway was introduced in November 2017 to allow incorporation of FIT into clinical practice. The local '4F' protocol combined FIT results with blood tests and digital rectal examination (DRE): FIT, full blood count, ferritin and finger [DRE]. The outcome used was detection rates of CRC, missed CRC and time to diagnosis in local 4F protocols for patients with a subthreshold faecal haemoglobin (fHb) result compared with thresholds of 10 and 20 µg Hb/g faeces. RESULTS: A single threshold of 10 µg Hb/g faeces identifies a population in whom the risk of CRC is 0.2%, but this would have missed 63 (10.5%) of 599 CRCs in this population. The Nottingham 4F protocol would have missed fewer CRCs [42 of 599 (7%)] despite using a threshold of 20 µg Hb/g faeces for patients with normal blood tests. Subthreshold FIT results in patients subsequently diagnosed with a palpable rectal tumour yielded the longest delays in diagnosis. CONCLUSION: A combination of FIT with blood results and DRE (the 4F protocol) reduced the risk of missed or delayed diagnosis. Further studies on the impact of such protocols on the diagnostic accuracy of FIT are expected. The value of adding blood tests to FIT may be restricted to specific parts of the fHb results spectrum.

Regional variations and deprivation are linked to poorer access to laparoscopic and robotic colorectal surgery: a national study in England.

BACKGROUND: Laparoscopic and now robotic colorectal surgery has rapidly increased in prevalence; however, little is known about how uptake varies by region and sociodemographics. The aim of this study was to quantify the uptake of minimally invasive colorectal surgery (MIS) over time and variations by region, sociodemographics and ethnicity. METHODS: Retrospective analysis of routinely collected healthcare data (Clinical Practice Research Datalink linked to Hospital Episode Statistics) for all adults having elective colorectal resectional surgery in England from 1 January 2006 to 31 March 2020. Sociodemographics between modalities were compared and the association between sociodemographic factors, region and year on MIS was compared in multivariate logistic regression analysis. RESULTS: A total of 93,735 patients were included: 52,098 open, 40,622 laparoscopic and 1015 robotic cases. Laparoscopic surgery surpassed open in 2015 but has plateaued; robotic surgery has rapidly increased since 2017, representing 3.2% of cases in 2019. Absolute differences up to 20% in MIS exist between regions, OR 1.77 (95% CI 1.68-1.86) in South Central and OR 0.75 (95% CI 0.72-0.79) in the North West compared to the largest region (West Midlands). MIS was less common in the most compared to least deprived (14.6% of MIS in the most deprived, 24.8% in the least, OR 0.85 95% CI 0.81-0.89), with a greater difference in robotic surgery (13.4% vs 30.5% respectively). Female gender, younger age, less comorbidity, Asian or 'Other/Mixed' ethnicity and cancer indication were all associated with increased MIS. CONCLUSIONS: MIS has increased over time, with significant regional and socioeconomic variations. With rapid increases in robotic surgery, national strategies for procurement, implementation, equitable distribution and training must be created to avoid worsening health inequalities.

Measuring executive function in sheep (Ovis aries) using visual stimuli in a semi-automated operant system.

BACKGROUND: Cognitive impairment is a distinguishing feature of many neurodegenerative diseases. The intra-dimensional (ID) extra-dimensional (ED) attentional set shift task is part of a clinical battery of tests used to evaluate executive function in Huntington's and Alzheimer's disease patients. The IDED task, however, has not translated well to pre-clinical rodent models of neurological disease. NEW METHOD: The ability to perform executive tasks coupled with a long lifespan makes sheep (Ovis aries) an ideal species for modelling cognitive decline in progressive neurodegenerative conditions. We describe the methodology for testing the performance of sheep in the IDED task using a semi-automated system in which visual stimuli are presented as coloured letters on computer screens. RESULTS: During each stage of IDED testing, all sheep (n = 12) learned successfully to discriminate between different colours and letters. Sheep were quick to learn the rules of acquisition at each stage. They required significantly more trials to reach criterion (p < 0.05) and made more errors (p < 0.05) following stimulus reversal, with the exception of the ED shift (p > 0.05). COMPARISON WITH EXISTING METHOD(S): Previous research shows that sheep can perform IDED set shifting in a walk-through maze using solid objects with two changeable dimensions (colour and shape) as the stimuli. Presenting the stimuli on computer screens provides better validity, greater task flexibility and higher throughput than the walk-through maze. CONCLUSION: All sheep completed each stage of the task, with a range of abilities expected in an outbred population. The IDED task described is ideally suited as a quantifiable and clinically translatable measure of executive function in sheep.

Characteristic patterns of EEG oscillations in sheep (Ovis aries) induced by ketamine may explain the psychotropic effects seen in humans.

Ketamine is a valuable anaesthetic and analgesic that in recent years has gained notoriety as a recreational drug. Recently, ketamine has also been proposed as a novel treatment for depression and post-traumatic stress disorder. Beyond its anaesthetic actions, however, the effects of ketamine on brain activity have rarely been probed. Here we examined the cortical electroencephalography (EEG) response to ketamine of 12 sheep. Following ketamine administration, EEG changes were immediate and widespread, affecting the full extent of the EEG frequency spectrum measured (0-125 Hz). After recovery from sedation during which low frequency activity dominated, the EEG was characterised by short periods (2-3 s) of alternating low (<14 Hz) and high (>35 Hz) frequency oscillation. This alternating EEG rhythm phase is likely to underlie the dissociative actions of ketamine, since it is during this phase that ketamine users report hallucinations. At the highest intravenous dose used (24 mg/kg), in 5/6 sheep we observed a novel effect of ketamine, namely the complete cessation of cortical EEG activity. This persisted for up to several minutes, after which cortical activity resumed. This phenomenon is likely to explain the 'k-hole', a state of oblivion likened to a near death experience that is keenly sought by ketamine abusers.

Antagonistic pleiotropy in mice carrying a CAG repeat expansion in the range causing Huntington's disease.

Antagonist pleiotropy, where a gene exerts a beneficial effect at early stages and a deleterious effect later on in an animal's life, may explain the evolutionary persistence of devastating genetic diseases such as Huntington's disease (HD). To date, however, there is little direct experimental evidence to support this theory. Here, we studied a transgenic mouse carrying the HD mutation with a repeat of 50 CAGs (R6/2_50) that is within the pathological range of repeats causing adult-onset disease in humans. R6/2_50 mice develop characteristic HD brain aggregate pathology, with aggregates appearing predominantly in the striatum and cortex. However, they show few signs of disease in their lifetime. On the contrary, R6/2_50 mice appear to benefit from carrying the mutation. They have extended lifespans compared to wildtype (WT) mice, and male mice show enhanced fecundity. Furthermore, R6/2_50 mice outperform WT mice on the rotarod and show equal or better performance in the two choice discrimination task than WT mice. This novel mouse line provides direct experimental evidence that, although the HD mutation causes a fatal neurodegenerative disorder, there may be premorbid benefits of carrying the mutation.

Lentiviral-based reporter constructs for profiling chondrogenic activity in primary equine cell populations.

Successful clinical translation of mesenchymal stem cell (MSC)-based therapies for cartilage repair will likely require the implementation of standardised protocols and broadly applicable tools to facilitate the comparisons among cell types and chondroinduction methods. The present study investigated the utility of recombinant lentiviral reporter vectors as reliable tools for comparing chondrogenic potential among primary cell populations and distinguishing cellular-level variations of chondrogenic activity in widely used three-dimensional (3D) culture systems. Primary equine MSCs and chondrocytes were transduced with vectors containing combinations of fluorescent and luciferase reporter genes under constitutive cytomeglavirus (CMV) or chondrocyte-lineage (Col2) promoters. Reporter activity was measured by fluorescence imaging and luciferase assay. In 3D cultures of MSC aggregates and polyethylene glycol-hyaluronic acid (PEG-HA) hydrogels, transforming growth factor beta 3 (TGF-ß3)-mediated chondroinduction increased Col2 reporter activity, demonstrating close correlation with histology and mRNA expression levels of COL2A1 and SOX9. Comparison of chondrogenic activities among MSC populations using a secretable luciferase reporter revealed enhanced chondrogenesis in bone-marrow-derived MSCs relative to MSC populations from synovium and adipose tissues. A dual fluorescence reporter - enabling discrimination of highly chondrogenic (Col2-GFP) cells within an MSC population (CMV-tdTomato) - revealed marked heterogeneity in differentiating aggregate cultures and identified chondrogenic cells in chondrocyte-seeded PEG-HA hydrogels after 6 weeks in a subcutaneous implant model - indicating stable, long-term reporter expression in vivo. These results suggested that lentiviral reporter vectors may be used to address fundamental questions regarding chondrogenic activity in chondroprogenitor cell populations and accelerate clinical translation of cell-based cartilage repair strategies.

Erratum to: Large-Brained Animal Models of Huntington's Disease: Sheep.

The name of the Chapter 12 author had been inadvertently mentioned as "Jennifer Morton A". This has been correctly updated as "Morton. A. J".

Large-Brained Animal Models of Huntington's Disease: Sheep.

The limitations of using small-brained rodents to model diseases that affect large-brain humans are becoming increasingly obvious as novel therapies emerge. Huntington's disease (HD) is one such disease. In recent years, the desirability of a large-brained, long-lived animal model of HD for preclinical testing has changed into a necessity. Treatment involving gene therapy in particular presents delivery challenges that are currently unsolved. Models using long-lived, large-brained animals would be useful, not only for refining methods of delivery (particularly for gene and other therapies that do not involve small molecules) but also for measuring long-term "off-target" effects, and assessing the efficacy of therapies. With their large brains and convoluted cortices, sheep are emerging as feasible experimental subjects that can be used to bridge the gap between rodents and humans in preclinical drug development. Sheep are readily available, economical to use, and easy to care for in naturalistic settings. With brains of a similar size to a large rhesus macaque, they have much to offer. The only thing that was missing until recently was the means of testing their neurological function and behavior using approaches and methods that are relevant to HD. In this chapter, I will outline the present and future possibilities of using sheep and testing as large animal models of HD.

Reconstruction of a Damaged Lower Polar Artery for Kidney Transplantation Using Tubularised Donor Aorta.

INTRODUCTION: Live donors, extended donor criteria, and the maximum usage of organs with anatomical variants are some of the mechanisms used to increase the number of organs available. CASE: We present the case of a kidney transplant, in which the organ had an iatrogenic injury to a lower pole arterial branch during retrieval. The donor was a 35-year-old male (DCD, Maastricht III). The right kidney was accepted; it had three veins in a single cava patch and three renal arteries, the main artery with aorta patch that is 8 cm long. A small lower pole artery was sectioned during retrieval surgery at approximately 1 cm from its origin as well as a third small mid-lower pole artery. The lower pole damaged artery was reconstructed using tubularised aorta patch to a total length of 5 cm. No additional donor vessels had been sent. After construction of the tubulised aorta, E-E anastomosis to the damaged polar artery was done with interrupted 7-0 Prolene sutures. CONCLUSION: While the waiting list for a kidney continues to rise and we continue to have organ shortness, vascular retrieval injury should not be an absolute contraindication for transplant.

Techniques for chronic monitoring of brain activity in freely moving sheep using wireless EEG recording.

BACKGROUND: Large mammals with complex central nervous systems offer new possibilities for translational research into basic brain function. Techniques for monitoring brain activity in large mammals, however, are not as well developed as they are in rodents. NEW METHOD: We have developed a method for chronic monitoring of electroencephalographic (EEG) activity in unrestrained sheep. We describe the methods for behavioural training prior to implantation, surgical procedures for implantation, a protocol for reliable anaesthesia and recovery, methods for EEG data collection, as well as data pertaining to suitability and longevity of different types of electrodes. RESULTS: Sheep tolerated all procedures well, and surgical complications were minimal. Electrode types used included epidural and subdural screws, intracortical needles and subdural disk electrodes, with the latter producing the best and most reliable results. The implants yielded longitudinal EEG data of consistent quality for periods of at least a year, and in some cases up to 2 years. COMPARISON WITH EXISTING METHODS: This is the first detailed methodology to be described for chronic brain function monitoring in freely moving unrestrained sheep. CONCLUSIONS: The developed method will be particularly useful in chronic investigations of brain activity during normal behaviour that can include sleep, learning and memory. As well, within the context of disease, the method can be used to monitor brain pathology or the progress of therapeutic trials in transgenic or natural disease models in sheep.

Integrative veterinary medical education and consensus guidelines for an integrative veterinary medicine curriculum within veterinary colleges.

Integrative veterinary medicine (IVM) describes the combination of complementary and alternative therapies with conventional care and is guided by the best available evidence. Veterinarians frequently encounter questions about complementary and alternative veterinary medicine (CAVM) in practice, and the general public has demonstrated increased interest in these areas for both human and animal health. Consequently, veterinary students should receive adequate exposure to the principles, theories, and current knowledge supporting or refuting such techniques. A proposed curriculum guideline would broadly introduce students to the objective evaluation of new veterinary treatments while increasing their preparation for responding to questions about IVM in clinical practice. Such a course should be evidence-based, unbiased, and unaffiliated with any particular CAVM advocacy or training group. All IVM courses require routine updating as new information becomes available. Controversies regarding IVM and CAVM must be addressed within the course and throughout the entire curriculum. Instructional honesty regarding the uncertainties in this emerging field is critical. Increased training of future veterinary professionals in IVM may produce an openness to new ideas that characterizes the scientific method and a willingness to pursue and incorporate evidence-based medicine in clinical practice with all therapies, including those presently regarded as integrative, complementary, or alternative.

Complications of percutaneous nephrolithotomy in the prone position according with modified Clavien-Dindo grading system.

INTRODUCTION: Clavien-Dindo classification system has been proposed to grade perioperative complications in percutaneous nephrolithotomy. The complications of this technique that have taken place in the last 2 years are reported in this paper according Clavien-Dindo classification. MATERIALS AND METHODS: Between 2011 and 2012 a total of 255 percutaneous nephrolithotomy were performed at our center for stones more than 2 cm in size. In order to determine the incidence of complications classified in the modified Clavien-Dindo system, statistical analysis of the data obtained was carried out. RESULTS: During the period analyzed, 255 percutaneous nephrolithotomy were performed in 249 patients, 41% of the right side, 57% of the left side and 2% bilateral and simultaneous. 137 and 112 patients were males and females, respectively. The most prevalent comorbidities were: hypertension (AHT) in 101 patients (40.6%), BMI>30 in 81 patients (32%), diabetes mellitus in 46 patients (18.5%) and coagulation abnormalities in 24 patients (9.6%). A total of 70 cases (27.4%) were distributed according to Clavien-Dindo classification: grade i, 8.4%, grade ii 8.4%, grade iiia 4.4%, grade iiib 6% grade iva .8%, grade ivb: 0% and grade v 0%. CONCLUSIONS: A graded classification scheme for reporting the complications of percutaneous nephrolithotomy is useful for monitoring and reporting outcomes. We propose a standardized use of this classification in order to make the results comparable among different centers performing the technique.

Understanding the concept of a reflective surface: can sheep improve navigational ability through the use of a mirror?

Mirror image-induced stimulation and the ability to use the mirror to improve navigational ability for the purpose of object location are considered measures of animal cognitive ability. The purpose of this study was to assess these cognitive abilities in sheep (Ovis aries) as part of a larger programme profiling the cognitive ability of this animal species. Three separate groups of sheep [(n = 29); 10 Welsh Mountain, 8 Norfolk Horned and 11 Borderdale] were trained (≥80 % criterion) to locate a salient object (yellow bucket containing cereal-based food) in one of two possible positions, from one of two possible starting points. Each group of sheep was then divided into two sub-groups. One sub-group was exposed to a mirror over a period of 15 days (mirror exposed), whilst the other group remained mirror naïve. All animals were then retested within the choice maze using the mirror, where two out of the possible four bucket positions were now 'apparent' (as reflections in the mirror), in order to assess whether mirror-exposed animals had a more accurate representation of the real bucket position. Sheep exhibited two out of the three archetypal stages of mirror-induced behaviour, namely social/exploratory and contingency behaviour, with differences existing between breeds. Welsh Mountain sheep spent significantly more time fixating on the self-image and touching the self-image with their muzzle than the other two breeds. During the test phase, no overall differences in performance were observed between the mirror-exposed and mirror-naïve groups. However, Welsh Mountain sheep did perform significantly more correct responses overall, compared to the other two breeds. Although the data did not convincingly demonstrate that sheep could use a reflective surface to improve their navigational ability, the observed differences between groups suggests that some breeds of sheep may demonstrate better navigational ability as well as having a greater engagement with the self-image than others.

Hinged circular fixator construct for correction of congenital metatarsal deformity in a foal.

A five-week-old American Quarter Horse colt was presented for evaluation of a left hindlimb deformity and lameness. Radiographs of the left hindlimb revealed a varus deformity with recurvatum originating in the mid-diaphysis of the third metatarsal bone. Surgical correction was undertaken by performing an osteotomy through the centre of rotation of angulation located within the mid-diaphysis of the third metatarsal bone, and a four-ring hinged circular external fixator construct was applied. Distraction of the osteotomy site was performed over an 11 day period. Notable complications included failure of a fixation pin, infection of the surgical site, and temporary laxity of the supporting tendons and ligaments of the contralateral metatarsophalangeal joint. The fixator was maintained until there was sufficient bone formation to allow frame removal, 152 days after the initial surgery. Use of a hinged circular construct allowed for partial correction of the deformity with resultant lengthening and resolution of the lameness in this colt.

Mucosal injury and inflammatory cells in response to brief ischaemia and reperfusion in the equine large colon.

REASON FOR PERFORMING STUDY: Intestinal ischaemia and reperfusion (I/R) can activate inflammatory cells in the equine colon, although effects on different types of inflammatory cells have received little attention. OBJECTIVES: To assess early mucosal injury, the reaction of mucosal neutrophils, eosinophils, mast cells and macrophages, and cyclooxygenase (COX)-1 and -2 expression in response to I/R in the equine large colon. METHODS: Large colon ischaemia was induced for 1 h (1hI) followed by 4 h of reperfusion in 6 horses, and mucosal biopsies were sampled before and after ischaemia, and after 1, 2 and 4 h of reperfusion. Semithin sections (500 nm) of epon-embedded biopsies were stained with toluidine blue for histomorphometric evaluation. The number and distribution of mucosal macrophages (CD163), neutrophils (calprotectin), eosinophils (LUNA) and mast cells (toluidine blue) were determined, and mucosal COX-1 and -2 expression was identified. RESULTS: Ischaemia caused epithelial cell and nuclear swelling (mean ± s.e. nuclear width; control: 2.7 ± 0.2 µm vs. 1hI: 4.2 ± 0.2 µm; P<0.01), subepithelial oedema (control: 0.2 ± 0.1 µm vs. 1hI: 3.2 ± 0.2 µm; P<0.01) and increased epithelial apoptosis (control: 14.3 ± 4.1 apoptotic cells/mm mucosa vs. 1hI: 60.4 ± 14.0 apoptotic cells/mm mucosa; P<0.01). COX-2 expression (P<0.01) was evident after ischaemia. Reperfusion caused paracellular fluid accumulation (control: 0.9 ± 0.1 µm vs. 1hI: 0.6 ± 0.6 µm vs. 1hI + 4hR: 1.6 ± 0.2 µm; P<0.05). Epithelial repair started at 1 h of reperfusion (P<0.001), followed by migration of neutrophils into the mucosa after 2 h (control: 72.3 ± 18.4 cells/mm(2) mucosa vs. 1hI + 2hR: 1149.9 ± 220.6 cells/mm(2) mucosa; P<0.01). Mucosal eosinophils, mast cells and macrophages did not increase in numbers but were activated. CONCLUSIONS: Epithelial injury and COX-2 expression caused by short-term hypoxia were followed by intense inflammation associated with epithelial repair during reperfusion. POTENTIAL RELEVANCE: Equine colonic mucosa subjected to a brief period of ischaemia can repair during reperfusion, despite increased mucosal inflammation.

Ultrastructural changes in the equine colonic mucosa after ischaemia and reperfusion.

REASON FOR PERFORMING STUDY: Ultrastructural changes in the epithelium can provide information on early changes in barrier properties, repair and inflammation in equine colon after ischaemia and reperfusion (I/R). OBJECTIVES: To describe the morphology and ultrastructure of the epithelium in equine large colonic mucosa after I/R, and the response of inflammatory cells to injury. METHODS: Ischaemia was induced for 1 h followed by 4 h of reperfusion in a 40 cm segment of the pelvic flexure in 6 horses. Mucosal biopsies before and after ischaemia, and after 1, 2 and 4 h of reperfusion were fixed in glutaraldehyde/paraformaldehyde and osmium tetroxide, and embedded in epon. Morphological and ultrastructural changes were evaluated in toluidine blue-stained semithin sections by light microscopy and in thin sections stained with uranyl acetate/lead citrate by transmission electron microscopy. RESULTS: Ischaemia caused swelling of epithelial cells and their organelles, opening of tight junctions, detachment from the basement membrane, early apoptosis and single cell necrosis. Autophagy was a prominent feature in epithelial cells after ischaemia. Reperfusion was characterised by apoptosis, epithelial regeneration and restoration of apical cell junctions. Phagocytic-like vacuoles containing cellular debris and bacteria were evident in epithelial cells after reperfusion. Paracellular and subepithelial clefts formed, accompanied by infiltration of neutrophils, lymphocytes and eosinophils into the epithelium. Subepithelial macrophages and luminal neutrophils had increased phagocytic activity. CONCLUSIONS: Ischaemia caused ultrastructural damage to the colonic epithelium, but epithelial cells recovered during reperfusion. POTENTIAL RELEVANCE: Transmission electron microscopy can demonstrate subtle ultrastructural damage to epithelial cells and evidence of recovery after I/R in equine colon.

Effects of flunixin meglumine on the recovery of ischaemic equine colonic mucosa in vitro.

REASONS FOR PERFORMING STUDY: The effects of prostaglandins and nonsteroidal anti-inflammatory drugs (NSAIDs) on repair of equine intestinal mucosa are important since most horses with gastrointestinal diseases are routinely treated with NSAIDs, such as flunixin meglumine (FM), and these drugs can be toxic to equine gastrointestinal mucosa. HYPOTHESIS: Flunixin meglumine would not affect recovery of equine colonic mucosa in vitro, 18 h after a reversible ischaemic injury. METHODS: In 14 anaesthetised horses, a segment of pelvic flexure was subjected to 2 h of ischaemia and the horses were allowed to recover for 18 h. Seven horses received normal saline and 7 received FM, 1.1 mg/kg bwt i.v., at the end of ischaemia and 12 h later. Colonic mucosa was harvested during a second anaesthesia, 18 h after recovery from ischaemia and then horses were subjected to euthanasia. Transepithelial electrical resistance (TER) and transepithelial flux of tritiated mannitol were used to measure mucosal permeability during 4 h of incubation in Ussing chambers, with the following in vitro treatments: 1) no addition, 2) FM 14 µmol/l as powder, 3) FM 14 µmol/l in injectable form and 4) diluent for injectable FM. Histomorphological changes were assessed by light microscopy. RESULTS: There were no significant differences in any of the measurements between saline and FM treated horses. The mucosal height of the ischaemic FM tissues incubated in diluent was significantly decreased compared to the nonischaemic tissues. CONCLUSIONS: Flunixin meglumine did not adversely affect barrier integrity in ischaemic equine colonic mucosa.

Cardiovascular effects of N-butylscopolammonium bromide and xylazine in horses.

REASONS FOR PERFORMING STUDY: N-butylscopolammonium bromide (NBB) and xylazine are commonly used medications for the treatment of spasmodic colic and other forms of abdominal pain in horses. Both NBB and xylazine exert significant effects on the cardiovascular system and other vital systems of horses. OBJECTIVE: To evaluate the effects of i.v. administration of NBB, xylazine, and the combination of NBB and xylazine on heart rate, other commonly measured physiological parameters, cardiac rhythm and blood pressure. METHODS: Six mature horses of mixed breed were used. In a random cross-over design, each horse was given 0.3 mg/kg bwt of NBB i.v., 0.25 mg/kg bwt xylazine i.v., and a combination of 0.3 mg/kg bwt NBB and 0.25 mg/kg bwt xylazine. Heart rate, physiological parameters, cardiac rhythm and indirect blood pressure were recorded at timed intervals before and 60 min following administration. RESULTS: Heart rate and blood pressure were significantly elevated immediately following administration of NBB or NBB with xylazine. Administration of NBB with xylazine resulted in significantly greater initial and peak blood pressure values than with NBB alone. Administration of xylazine resulted in a decrease in heart rate, with an initial increase in blood pressure followed by a decrease in blood pressure. Sinus tachycardia was seen with NBB, and NBB and xylazine administration. First and second degree atrioventricular block was identified with xylazine administration. Ventricular tachycardia was identified in one horse following NBB and xylazine administration. CONCLUSIONS: Results of this study suggest that the effects of administration of NBB alone or in combination with xylazine to horses with colic, especially to those with systemic cardiovascular compromise, should be considered carefully to assess condition and predict prognosis accurately, and to avoid potential adverse effects.

Use of magnetic resonance imaging for anatomical phenotyping of the R6/2 mouse model of Huntington's disease.

Huntington's disease (HD) is a fatal, inherited neurodegenerative CAG disorder characterized by marked brain atrophy. We used magnetic resonance imaging (MRI) with manual volumetry for three dimensional (3D) morphological phenotyping of ex vivo brains of R6/2 mice, the most commonly used model of HD. High resolution 3D images were acquired for 18 week old wild-type (WT) and R6/2 mice. Although overall brain volumes were the same between genotypes, decreases in volumes were found in the cortex and striatum of R6/2 mice, with significant volume increases in the lateral ventricles and globus pallidus. There was no change in the volume of the amygdala, internal capsule or hippocampal formation. There was a significant increase in signal intensity in the globus pallidus, amygdala, cortex and striatum in R6/2 mice that may reflect neuronal atrophy. This study clearly shows the potential of MRI for morphological phenotyping of rodent models of HD and other neurological diseases. Having obtained proof-of-principle for the technique using ex vivo tissue, it is now our intention to carry out in vivo measurement of developing pathology in HD transgenic mice, and correlate this with behavioral deficits.