@article{little_tomlinson_blikslager_2005, title={Post operative neutrophilic inflammation in equine small intestine after manipulation and ischaemia}, volume={37}, ISSN={["0425-1644"]}, DOI={10.2746/0425164054529472}, abstractNote={REASONS FOR PERFORMING STUDY
Post operative ileus (POI) remains an important cause of post operative morbidity and mortality in the horse. However, clinical progression of naturally occurring cases of POI in both horse and man does not entirely support the 'neurogenic' hypothesis as the sole mechanism of POI; and the hypothesis that inflammation plays a major role at 12-24 h after surgery requires validation.


HYPOTHESIS
An inflammatory infiltrate in the muscularis externa and myenteric plexus of equine jejunum is present 18 h following a period of ischaemia.


METHODS
Samples of normal jejunum, jejunum from the proximal resection margins of clinical cases and jejunum obtained 18 h after 1 or 2 h ischaemia or manipulation alone were evaluated for neutrophil infiltration. Samples obtained 18 h after surgery were additionally evaluated for leucocyte activation using calprotectin immunohistochemistry. Results were evaluated by ANOVA and P < 0.05 was considered significant.


RESULTS
Significant neutrophilic inflammation was identified in the samples from the proximal resection margins of clinical cases compared to uninjured jejunum. In experimental cases, neutrophilic inflammation appeared to be increased further by 18 h and was identified through all intestinal layers, particularly in the serosa, fascial planes around circular and longitudinal muscle fibres, and myenteric plexus. This elevated level of neutrophilic inflammation was mirrored by an increased number of calprotectin-positive cells in these intestinal layers, indicating leucocyte activation.


CONCLUSIONS
Significant neutrophilic inflammation occurs in equine jejunal myenteric layers 18 h after surgery.


POTENTIAL RELEVANCE
This neutrophilic inflammation coincides with the clinical time point at which POI is identified and may indicate that inflammatory pathways, rather than solely neurogenic pathways, are responsible for POI in the horse.}, number={4}, journal={EQUINE VETERINARY JOURNAL}, author={Little, D and Tomlinson, JE and Blikslager, AT}, year={2005}, month={Jul}, pages={329–335} }
 @article{tomlinson_blikslager_2005, title={Effects of cyclooxygenase inhibitors flunixin and deracoxib on permeability of ischaemic-injured equine jejunum}, volume={37}, ISSN={["2042-3306"]}, DOI={10.2746/0425164054406865}, abstractNote={SummaryReasons for performing study: Recent studies have shown that flunixin prevented recovery of equine jejunum post ischaemia. However, the use of a purported cyclooxygenase (COX)‐2 preferential inhibitor, etodolac, also prevented recovery. These findings may have implications for the use of nonsteroidal anti‐inflammatory drugs in colic patients.Objective: To compare the effects of deracoxib, a highly selective canine COX‐2 inhibitor, with flunixin onin vitrorecovery of ischaemic‐injured equine jejunum.Methods: Six horses underwent 2 h jejunal ischaemia, after which mucosa was mounted in Ussing chambers and recovered for 240 mins. Transepithelial electrical resistance (TER) and mucosal‐to‐serosal fluxes of3H‐mannitol were monitored as indices of barrier function in the presence of flunixin or deracoxib.Results: The TER of ischaemic‐injured tissue recovered significantly over 240 mins in the presence of no treatment, but not in the presence of flunixin or deracoxib. In addition, flunixin‐treated ischaemic jejunum was significantly more permeable to mannitol when compared with untreated tissue by the end of the recovery period, whereas deracoxib treatment did not increase permeability. Addition of the PGE1analogue misoprostol to flunixin‐treated tissue restored recovery of TER.Conclusions and potential relevance: Treatment of horses with ischaemic jejunal disease with flunixin may result in a prolonged permeability defect in recovering mucosa. Addition of misoprostol or replacement of flunixin with deracoxib may ameliorate effects of COX inhibitors on recovering mucosa.}, number={1}, journal={EQUINE VETERINARY JOURNAL}, author={Tomlinson, JE and Blikslager, AT}, year={2005}, month={Jan}, pages={75–80} }
 @article{tomlinson_wilder_young_blikslager_2004, title={Effects of flunixin meglumine or etodolac treatment on mucosal recovery of equine jejunum after ischemia}, volume={65}, ISSN={["1943-5681"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-3042571674&partnerID=MN8TOARS}, DOI={10.2460/ajvr.2004.65.761}, abstractNote={AbstractObjective—To examine the effects of flunixin meglumine and etodolac treatment on recovery of ischemicinjured equine jejunal mucosa after 18 hours of reperfusion.Animals—24 horses.Procedure—Jejunum was exposed to 2 hours of ischemia during anesthesia. Horses received saline (0.9% NaCl) solution (12 mL, IV, q 12 h), flunixin meglumine (1.1 mg/kg, IV, q 12 h), or etodolac (23 mg/kg, IV, q 12 h). Tissue specimens were obtained from ischemic-injured and nonischemic jejunum immediately after ischemia and 18 hours after recovery from ischemia. Transepithelial electric resistance (TER) and transepithelial flux of tritium-labeled mannitol measured mucosal permeability. Denuded villous surface area and mean epithelial neutrophil count per mm2 were calculated. Western blot analysis for cyclooxygenase (COX)-1 and -2 was performed. Pharmacokinetics of flunixin and etodolac and eicosanoid concentrations were determined.Results—Ischemic-injured tissue from horses treated with flunixin and etodolac had significantly lower TER and increased permeability to mannitol, compared with that from horses treated with saline solution. Epithelial denudation after ischemia and 18 hours after recovery was not significantly different among treatments. Both COX-1 and -2 were expressed in ischemic-injured and nonischemic tissues. Ischemia caused significant upregulation of both COX isoforms. Eicosanoid concentrations were significantly lower in tissues from flunixin and etodolac-treated horses, compared with that from horses treated with saline solution.Conclusions and Clinical Relevance—Flunixin and etodolac treatment retarded recovery of intestinal barrier function in jejunal mucosa after 18 hours of reperfusion, whereas tissues from horses treated with saline solution recovered baseline values of TER and permeability to mannitol. (Am J Vet Res2004;65:761–769)}, number={6}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Tomlinson, JE and Wilder, BO and Young, KM and Blikslager, AT}, year={2004}, month={Jun}, pages={761–769} }
 @article{tomlinson_blikslager_2004, title={Effects of ischemia and the cyclooxygenase inhibitor flunixin on in vitro passage of lipopolysaccharide across equine jejunum}, volume={65}, ISSN={["0002-9645"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-5644271864&partnerID=MN8TOARS}, DOI={10.2460/ajvr.2004.65.1377}, abstractNote={AbstractObjective—To determine whether ischemia and flunixin affect in vitro lipopolysaccharide (LPS) absorption in samples of the jejunum of horses.Animals—12 horses.Procedure—Horses were anesthetized, a midline celiotomy was performed, and the jejunum was located. Two 30-cm sections of jejunum (60 cm apart) were selected. One segment was designated as control tissue; ischemia was induced in the other segment for 120 minutes. Horses were then euthanatized. Mucosa from each jejunal segment was mounted on Ussing chambers and treated with or without flunixin. Tissues from 6 horses were used to assess permeability to radiolabeled LPS; mucosal samples from the remaining 6 horses were incubated with fluorescent-labeled LPS (FITC-LPS) and examined histologically. Production of tumor necrosis factor-α (TNF-α) and production of LPS-binding protein (LBP) were assessed as indicators of mucosal response to LPS.Results—Ischemia significantly increased mucosal permeability to LPS, but by 180 minutes, the mucosa was not more permeable than control tissue. Flunixin treatment adversely affected intestinal barrier function throughout the experiment but did not result in increased mucosal permeability to LPS. Compared with control tissues, LBP production was increased by ischemia and reduced by exposure to LPS. In ischemic tissue, FITC-LPS entered the lamina propria but TNF-α was produced on the mucosal side only, indicating little response to the absorbed LPS.Conclusions and Clinical Relevance—Ischemia increased LPS passage across equine jejunal mucosa. Flunixin delayed mucosal recovery but did not exacerbate LPS absorption. Evaluation of the clinical importance of flunixin-associated delayed mucosal recovery requires further in vivo investigation. (Am J Vet Res2004;65:1377–1383)}, number={10}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Tomlinson, JE and Blikslager, AT}, year={2004}, month={Oct}, pages={1377–1383} }
 @article{tomlinson_blikslager_2004, title={Interactions between lipopolysaccharide and the intestinal epithelium}, volume={224}, ISSN={["1943-569X"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-2442581583&partnerID=MN8TOARS}, DOI={10.2460/javma.2004.224.1446}, abstractNote={I ischemia often results in endotoxemia, and endotoxemia significantly increases postoperative morbidity and mortality rates in patients with ischemic intestinal disease. Even if all grossly ischemic intestine is resected, remaining intestine may be injured as a result of distention. In addition, intestine at the margins of the resection may have evidence of serosal injury and neutrophil infiltration. Endotoxemia is a result of absorption of lipopolysaccharide (LPS) from intestinal gram-negative bacteria. Gram-negative bacteria release LPS during periods of rapid proliferation and cell death. Once absorbed, LPS stimulates host cells, principally monocytes and macrophages, to produce and release endogenous mediators of inflammation, triggering pathophysiologic effects that range from mild fever to fatal septic shock. Although intestinal epithelial cells were once regarded as merely a barrier to LPS, it has recently been determined that these cells interact specifically with LPS molecules. Intestinal epithelial cells are normally exposed to high numbers of intact bacteria and high concentrations of bacterial products and form a barrier to LPS absorption and intestinal microbial invasion. As a result, intestinal epithelial cells must recognize and react to pathologic bacteria but avoid responding to the normal gastrointestinal tract flora. Inappropriate responses to normal gastrointestinal tract flora likely play a role in the development of inflammatory bowel disease. Intestinal epithelial cells are regularly exposed to LPS, and small amounts of LPS may be found in the portal blood of healthy individuals. Kupffer cells in the liver typically remove this LPS before it can reach the systemic circulation. However, if the amount of LPS in the portal blood overwhelms the liver’s mechanisms for LPS removal, then LPS will enter the systemic circulation. Circulating LPS interacts with host cells via specific cell surface receptors, and the intercalation of these molecules is considered to be an important step in the activation cascade.}, number={9}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Tomlinson, JE and Blikslager, AT}, year={2004}, month={May}, pages={1446–1452} }
 @article{tomlinson_redding_berry_smallwood_2003, title={Computed tomographic anatomy of the equine tarsus}, volume={44}, ISSN={["1058-8183"]}, DOI={10.1111/j.1740-8261.2003.tb01267.x}, abstractNote={The purpose of this study was to provide a detailed computed tomographic (CT) anatomic reference for the equine tarsus. CT exami‐nations of the tarsal regions from four cli‐nically and radiographically normal adult horses, which were euthanized for reasons not related to musculoskeletal disease, were included in the study. Limbs were removed at the level of midtibia, and 3‐mni contiguous transverse CT images were obtained, starting at a level proximal to the tuber calcanei and con‐tinuing distally into the proximal metatarsus. Soft tissue and bone windows were used to image different anatomic features, including bones, joints, and various soft tissue components of the tarsus. Each transverse slice was compared with bone models and dissected specimens to assist in the accurate identification of spe‐cific structures. The results of the study consist of nine CT images of the equine tarsus. Each image incorporates labeled soft tissue and bone‐window images, a directional compass indi‐cating cranial (Cr) or dorsal (D) and lateral (L), and a reconstructed scout image indicating the level through which the transverse slice was made.}, number={2}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Tomlinson, JE and Redding, WR and Berry, C and Smallwood, JE}, year={2003}, pages={174–178} }
 @article{tomlinson_sage_turner_2003, title={Ultrasonographic abnormalities detected in the sacroiliac area in twenty cases of upper hindlimb lameness}, volume={35}, ISSN={["0425-1644"]}, DOI={10.2746/042516403775467540}, abstractNote={SummaryReasons for performing study: The pelvis is covered with extensive musculature and often presents a challenge in diagnostic imaging. Ultrasonography provides diagnostic information about soft tissue, articular cartilage and bone surfaces, although little information exists about the normal ultrasonographic appearance of the equine sacroiliac region.Objectives: To determine the clinical applicability of ultrasonographic examination in horses with sacroiliac pain.Methods: Horses presented to the University of Minnesota Veterinary Teaching Hospital for hindlimb lameness were evaluated and lower limb lameness was ruled out with examination and local anaesthesia. Twenty cases were diagnosed with sacroiliac pain, characterised by response to palpation over thetuber sacrale.Seven of the 20 had visible a symmetry of thetuber sacrale.Ultrasonography was performed percutaneously andper rectum.Structures imaged were measured and compared to normal reference measurements. Other methods used to confirm diagnoses included thermography, scintigraphy and radiology.Results: All 20 cases with sacroiliac pain showed ultrasonographic abnormalities of the sacroiliac area. Abnormalities were detected in the dorsal sacroiliac ligaments. Ligament size was significantly different from the normal ranges (P<0.01). Malalignment of the sacroiliac area and sacral fractures were also imaged.Conclusions: Ultrasonography of the sacroiliac region aided diagnosis of ligament damage and displacement of bone surfaces; and may aid in monitoring the progression of healing.Potential relevance: Diagnostic ultrasound is readily available to most practitioners. Therefore the findings of this study show that diagnosis of sacroiliac injuries is possible in the field.}, number={1}, journal={EQUINE VETERINARY JOURNAL}, author={Tomlinson, JE and Sage, AM and Turner, TA}, year={2003}, month={Jan}, pages={48–54} }
 @article{tomlinson_sage_turner_feeney_2001, title={Detailed ultrasonographic mapping of the pelvis in clinically normal horses and ponies}, volume={62}, ISSN={["0002-9645"]}, DOI={10.2460/ajvr.2001.62.1768}, abstractNote={AbstractObjective—To map the equine pelvis using ultrasonography, validated by use of computed tomography (CT), magnetic resonance imaging (MRI), and measurements of frozen cadaver slices.Animals—6 ponies and 6 horses.Procedure—Ultrasonographic examination of the pelvis was performed on 6 clinically normal ponies. Measurements were obtained for imaged structures. Computed tomography, MRI, and measurements of frozen sections were performed after death and used to verify measurements. Linear regression determined the degree of correlation between measurements obtained ultrasonographically and the other modalities. Six clinically normal horses were then examined by use of ultrasonography. For each structure measured mean, SD, and range were calculated.Results—Data obtained from ponies revealed high correlations between ultrasonographic findings and those of CT, MRI, and frozen section measurements (r2= 0.97,r2= 0.99, andr2= 0.99, respectively). Differences between structures measured on each side of the pelvis were not significant. Variation in size of structures was not associated with weight of horses. A correlation was not found between weight of horses and ponies and size of structure.Conclusions and Clinical Relevance—Ultrasonography can be used to accurately measure and evaluate the musculoskeletal structures of the pelvis of horses. The use of CT, MRI, and measurements of frozen sections provided a means of validating the ultrasonographic measurements. Reference range values determined in our study can be used to evaluate horses with suspected pelvic disease. (Am J Vet Res2001;62:1768–1775)}, number={11}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Tomlinson, JE and Sage, AM and Turner, TA and Feeney, DA}, year={2001}, month={Nov}, pages={1768–1775} }