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C. C. Pollitt - One of the best experts on this subject based on the ideXlab platform.
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the oral glucose test predicts Laminitis risk in ponies fed a diet high in nonstructural carbohydrates
Domestic Animal Endocrinology, 2018Co-Authors: Alexandra Meier, M. A. De Laat, C. C. Pollitt, James Mcgree, Dania Birte Reiche, Donald M Walsh, M. N. SillenceAbstract:The aim of this study was to investigate the relationship between Laminitis development in ponies and insulin/glucose concentrations in response to the oral glucose test (OGT) and a dietary challenge high in nonstructural carbohydrates (NSCs). After undergoing an OGT (1 g dextrose/kg BW in feed), 37 ponies with 2-h serum insulin concentrations ranging from 22 to 1,133 μIU/mL were subjected to a diet challenge period (DCP), consuming 12 g NSC/kg BW/d for up to 18 d. Insulin and glucose responses were measured on day 2 of the DCP. Clinical Laminitis was diagnosed by blinded experts and confirmed radiographically. Basal ACTH levels and clinical signs were assessed to investigate concurrent putative pituitary pars intermedia dysfunction (PPID). The diet induced Obel grade 1 or 2 Laminitis in 14 ponies (38%). The ponies that developed Laminitis had higher maximum concentrations of blood glucose (P = 0.04) and serum insulin (P = 0.02) in response to the diet. The geometric mean (95% CI) blood glucose concentration for Laminitis cases was 14.9 (12.9-17.2) mM, compared to 10.7 (9.2-12.5) mM for ponies who did not develop Laminitis. Similarly, the geometric mean (95% CI) for serum insulin was 396 (301-520) μIU/mL for Laminitis cases, compared to 216 (148-316) μIU/mL for ponies who did not develop Laminitis. Laminitis incidence was likewise associated with insulin concentrations measured during the OGT. Laminitis occurred at frequencies of 0% (0/7) if postdextrose insulin (μIU/mL) was 195 μIU/mL. Basal ACTH concentrations were above seasonally accepted reference ranges in 16/37 ponies, and 8 of these animals (50%) developed Laminitis. This included all 5 ponies in the study that had clinical signs of PPID (100%). In contrast, hyperinsulinemia and Laminitis occurred in only 3/11 ponies (27%) with elevated ACTH concentrations and no clinical signs of PPID (P = 0.009). Thus, Laminitis occurrence was associated with higher glucose and insulin responses to both the OGT and challenge diet, and the frequency of Laminitis can be predicted based on insulin and glucose hyperresponsiveness to these oral carbohydrate challenges.
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distribution of technetium 99m peg liposomes during oligofructose induced Laminitis development in horses
Veterinary Journal, 2015Co-Authors: C Underwood, C. C. Pollitt, Josbert M Metselaar, Peter Laverman, Louis Van Bloois, Jolanda M Van Den Hoven, Gerrit StormAbstract:Liposomes are phospholipid nanoparticles used for targeted drug delivery. This study aimed to determine whether intravenous liposomes accumulate in lamellar tissue during Laminitis development in horses so as to assess their potential for targeted lamellar drug delivery. Polyethylene-glycol (PEG) coated liposomes were prepared according to the film hydration method and labelled using 99mTc-hexamethyl-propylene-amine-oxime. Six horses received 10 g/kg oligofructose via nasogastric tube to induce Laminitis, and four control horses received water via nasogastric tube. All horses received 300 µmol 99mTc-PEG-liposomes (5.5 GBq) plus 5.5 µmol/kg PEG-liposomes by slow intravenous infusion. Scintigraphic imaging was performed at 0, 6 and 12 h post-infusion. Technetium-99m liposome uptake was measured in regions of interest over the hoof, fetlock and metacarpus. At the study end-point horses were euthanased, tissue samples collected and tissue liposome levels were calculated as the percentage of the injected dose of 99mTc-liposomes per kilogram of tissue. Data were analysed non-parametrically. All horses receiving oligofructose developed clinical and histological signs of Laminitis. Technetium-99m liposome uptake in the hoof increased with time in Laminitis horses (P = 0.04), but decreased with time in control horses (P = 0.01). Technetium-99m liposome levels in lamellar tissue from Laminitis horses were 3.2-fold higher than controls (P = 0.02) and were also higher in Laminitis vs. control skin, muscle, jejunum, colon, and kidney (P < 0.05). Liposomes accumulated in lamellar tissue during oligofructose-induced Laminitis development and demonstrated potential for targeted lamellar drug delivery in acute Laminitis. This study provides further evidence that lamellar inflammation occurs during Laminitis development. Liposome accumulation also occurred in the skin, muscle, jejunum, colon and kidneys, suggesting systemic inflammation in this model.
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the timeline of metalloprotease events during oligofructose induced equine Laminitis development
Equine Veterinary Journal, 2012Co-Authors: Michelle B Visser, C. C. PollittAbstract:Reason for performing study: The role of matrix metalloproteases (MMPs) and the timeline of proteolysis during Laminitis development are incompletely understood. Objectives: To determine the temporal progression of selected MMPs and protease regulators during Laminitis development. Methods: Five clinically normal Standardbred horses received, via nasogastric intubation, an oligofructose (OF) bolus (10g/kg bwt). Laminitis induction proceeded for 48h followed by euthanasia. Lamellar biopsies were obtained prior to dosing and at intervals during the treatment period for analysis (12, 18, 24, 30 and 36h and at 48h following euthanasia). Tissue samples were analysed by real-time PCR, zymography and western blotting. Results: Activation of proMMP-2 occurs either simultaneously or at least 12h following lamellar basement membrane (BM) damage, while no activation of proMMP-9 is seen during OF Laminitis induction. Aggrecanase gene expression increased initially at 12-18h post OF dosing, similar to BM changes. Gene expression of TIMP-2, a MMP regulator, decreases during Laminitis development. Conclusions: The MMP-2/MT1-MMP complex may not play a major role in initiating lamellar BM damage. Aggrecanase and TIMP-2 gene expression appear related to BM lamellar changes. Potential relevance: MMPs, historically thought to cause Laminitis, do not appear to play an initiating role in the lamellar lesion. Other host derived proteases and degradation of alternative lamellar matrix components need to be considered.
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equine Laminitis comparative histopathology 48 hours after experimental induction with insulin or alimentary oligofructose in standardbred horses
Journal of Comparative Pathology, 2011Co-Authors: M. A. De Laat, C. M. Mcgowan, M. N. Sillence, C. C. PollittAbstract:Summary Laminitis has many triggers and comparing the histopathology of lesions induced by different causes may help to establish whether a common mechanism or multiple pathologies are involved. The aim of this study was to describe the microscopical lesions and to quantify morphometric changes in the lamellae of horses with insulin-induced (n = 4) and oligofructose (OF)-induced Laminitis (n = 4) compared with normal controls (n = 4). Archived lamellar samples collected during two previous studies were used. Laminitis was induced within 48 h in standardbred horses with either a euglycaemic, hyperinsulinaemic clamp (EHC) technique or, in a separate experiment, with an overdose of alimentary OF. Normal tissue was obtained from control horses in the EHC experiment that received a balanced electrolyte solution intravenously for 48 h. Six measurements of lamellar length and width were recorded for each hoof. Leucocyte infiltration was assessed by immunolocalization of calprotectin. All control horses exhibited normal lamellar architecture, whereas treated horses developed clinical and histopathological changes consistent with Laminitis. Laminitic samples displayed lengthening and narrowing of secondary epidermal lamellae (SELs), rounded epidermal basal cell (EBC) nuclei, mitosis and apoptosis. In the fore feet of laminitic horses, the length from the end of the keratinized axis to the axial tip of the primary epidermal lamellae (PELs) was increased (P
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the developmental and acute phases of insulin induced Laminitis involve minimal metalloproteinase activity
Veterinary Immunology and Immunopathology, 2011Co-Authors: M. A. De Laat, C. M. Mcgowan, M. N. Sillence, M T Kyawtanner, A R Nourian, C. C. PollittAbstract:Metalloproteinases have been implicated in the pathogenesis of equine Laminitis and other inflammatory conditions, through their role in the degradation and remodelling of the extracellular matrix environment. Matrix metalloproteinases (MMPs) and their inhibitors are present in normal equine lamellae, with increased secretion and activation of some metalloproteinases reported in horses with Laminitis associated with systemic inflammation. It is unknown whether these enzymes are involved in insulin-induced Laminitis, which occurs without overt systemic inflammation. In this study, gene expression of MMP-2, MMP-9, MT1-MMP, ADAMTS-4 and TIMP-3 was determined in the lamellar tissue of normal control horses (n = 4) and horses that developed Laminitis after 48 h of induced hyperinsulinaemia (n = 4), using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Protein concentrations of MMP-2 and MMP-9 were also examined using gelatin zymography in horses subject to prolonged hyperinsulinaemia for 6 h (n = 4), 12 h (n = 4), 24 h (n = 4) and 48 h (n = 4), and in normal control horses (n = 4). The only change in gene expression observed was an upregulation of MMP-9 (p < 0.05) in horses that developed insulin-induced Laminitis (48 h). Zymographical analysis showed an increase (p < 0.05) in pro MMP-9 during the acute phase of Laminitis (48 h), whereas pro MMP-2 was present in similar concentration in the tissue of all horses. Thus, MMP-2, MT1-MMP, TIMP-3 and ADAMTS-4 do not appear to play a significant role in the pathogenesis of insulin-induced Laminitis. The increased expression of MMP-9 may be associated with the infiltration of inflammatory leukocytes, or may be a direct result of hyperinsulinaemia. The exact role of MMP-9 in basement membrane degradation in Laminitis is uncertain as it appears to be present largely in the inactive form.
C. M. Mcgowan - One of the best experts on this subject based on the ideXlab platform.
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paradigm shifts in understanding equine Laminitis
Veterinary Journal, 2018Co-Authors: J C Pattersonkane, Ninja Karikoski, C. M. McgowanAbstract:Abstract Laminitis, one of the most debilitating conditions of all equids, is now known to be the result of several systemic disease entities. This finding, together with other recent developments in the field of Laminitis research, have provoked a rethink of our clinical and research strategies for this condition. First, Laminitis is now considered to be a clinical syndrome associated with systemic disease (endocrine disease, sepsis or systemic inflammatory response syndrome, SIRS) or altered weight bearing rather than being a discrete disease entity. Next, Laminitis associated with endocrine disease (endocrinopathic Laminitis) is now believed to be the predominant form in animals presenting (primarily) for lameness. Third, the designation of Laminitis as a primary and severe basement membrane pathology now requires revision. Instead, current data now proposes a variable subclinical phase associated with gross changes in the hoof capsule, with stretching and elongation of the lamellar cells an early and key event in the pathophysiology. These findings have fuelled new mechanistic hypotheses and research directions that will be discussed, together with their implications for future clinical management.
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pathology of natural cases of equine endocrinopathic Laminitis associated with hyperinsulinemia
Veterinary Pathology, 2015Co-Authors: Ninja Karikoski, C. M. Mcgowan, E R Singer, K E Asplin, Riittamari Tulamo, J C PattersonkaneAbstract:Laminitis in equids is a clinical syndrome usually associated with systemic disease. Endocrinopathies recently have been recognized as the most common cause of Laminitis, with hyperinsulinemia playing a key role. Descriptions of Laminitis-associated lesions have been confusing due to the wide range of experimental models used, failure of adequate clinical documentation for naturally occurring cases, lack of separate analysis of inflammatory and endocrinopathic Laminitis, and uncertainty regarding normal morphological variation of lamellae. In this study, lamellar morphology and pathology were described in 14 laminitic horses and ponies that had hyperinsulinemia (>20 mIU/l), with reference to 25 age- and breed-matched controls. The type and severity of lesions noted had no correlation with reported clinical duration and in at least some cases must have preceded it. Lesions were largely localized abaxially within the lamellar tissue and included apoptotic cell death, as well as lamellar fusion, hyperplasia,...
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equine Laminitis comparative histopathology 48 hours after experimental induction with insulin or alimentary oligofructose in standardbred horses
Journal of Comparative Pathology, 2011Co-Authors: M. A. De Laat, C. M. Mcgowan, M. N. Sillence, C. C. PollittAbstract:Summary Laminitis has many triggers and comparing the histopathology of lesions induced by different causes may help to establish whether a common mechanism or multiple pathologies are involved. The aim of this study was to describe the microscopical lesions and to quantify morphometric changes in the lamellae of horses with insulin-induced (n = 4) and oligofructose (OF)-induced Laminitis (n = 4) compared with normal controls (n = 4). Archived lamellar samples collected during two previous studies were used. Laminitis was induced within 48 h in standardbred horses with either a euglycaemic, hyperinsulinaemic clamp (EHC) technique or, in a separate experiment, with an overdose of alimentary OF. Normal tissue was obtained from control horses in the EHC experiment that received a balanced electrolyte solution intravenously for 48 h. Six measurements of lamellar length and width were recorded for each hoof. Leucocyte infiltration was assessed by immunolocalization of calprotectin. All control horses exhibited normal lamellar architecture, whereas treated horses developed clinical and histopathological changes consistent with Laminitis. Laminitic samples displayed lengthening and narrowing of secondary epidermal lamellae (SELs), rounded epidermal basal cell (EBC) nuclei, mitosis and apoptosis. In the fore feet of laminitic horses, the length from the end of the keratinized axis to the axial tip of the primary epidermal lamellae (PELs) was increased (P
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the prevalence of endocrinopathic Laminitis among horses presented for Laminitis at a first opinion referral equine hospital
Domestic Animal Endocrinology, 2011Co-Authors: Ninja Karikoski, I Horn, T W Mcgowan, C. M. McgowanAbstract:Endocrinopathic causes of Laminitis may be a common underlying causative pathogenesis in first-opinion or field cases presenting with Laminitis, as opposed to Laminitis produced in inflammatory research models. This study aimed to determine whether evidence of an underlying endocrinopathy was present in horses presented for Laminitis to a first-opinion/referral veterinary teaching hospital. A second aim was to compare the signalment of horses and ponies with Laminitis with the equine hospital population during the same period. All horses presenting for Laminitis at Helsinki University Equine Teaching Hospital, Finland, over a 16-month period were examined for an underlying endocrinopathy. Horses presenting for Laminitis were compared with the hospitalized population over the same period. There were 36 horses presented for Laminitis, and evidence of endocrinopathy was present in 89%. Of the horses showing an underlying endocrinopathy, one-third had a diagnosis of pituitary pars intermedia dysfunction, and two-thirds showed basal hyperinsulinemia indicative of insulin resistance, without evidence of hirsutism. Phenotypic indicators of obesity were present in 95% of horses with basal hyperinsulinemia without hirsutism. Compared with the hospital population during the same period, horses with Laminitis associated with an underlying endocrinopathy were significantly older and more likely to be pony breeds. Our data support that endocrine testing should be performed on all cases of Laminitis that do not have a clear inflammatory or gastrointestinal origin.
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the developmental and acute phases of insulin induced Laminitis involve minimal metalloproteinase activity
Veterinary Immunology and Immunopathology, 2011Co-Authors: M. A. De Laat, C. M. Mcgowan, M. N. Sillence, M T Kyawtanner, A R Nourian, C. C. PollittAbstract:Metalloproteinases have been implicated in the pathogenesis of equine Laminitis and other inflammatory conditions, through their role in the degradation and remodelling of the extracellular matrix environment. Matrix metalloproteinases (MMPs) and their inhibitors are present in normal equine lamellae, with increased secretion and activation of some metalloproteinases reported in horses with Laminitis associated with systemic inflammation. It is unknown whether these enzymes are involved in insulin-induced Laminitis, which occurs without overt systemic inflammation. In this study, gene expression of MMP-2, MMP-9, MT1-MMP, ADAMTS-4 and TIMP-3 was determined in the lamellar tissue of normal control horses (n = 4) and horses that developed Laminitis after 48 h of induced hyperinsulinaemia (n = 4), using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Protein concentrations of MMP-2 and MMP-9 were also examined using gelatin zymography in horses subject to prolonged hyperinsulinaemia for 6 h (n = 4), 12 h (n = 4), 24 h (n = 4) and 48 h (n = 4), and in normal control horses (n = 4). The only change in gene expression observed was an upregulation of MMP-9 (p < 0.05) in horses that developed insulin-induced Laminitis (48 h). Zymographical analysis showed an increase (p < 0.05) in pro MMP-9 during the acute phase of Laminitis (48 h), whereas pro MMP-2 was present in similar concentration in the tissue of all horses. Thus, MMP-2, MT1-MMP, TIMP-3 and ADAMTS-4 do not appear to play a significant role in the pathogenesis of insulin-induced Laminitis. The increased expression of MMP-9 may be associated with the infiltration of inflammatory leukocytes, or may be a direct result of hyperinsulinaemia. The exact role of MMP-9 in basement membrane degradation in Laminitis is uncertain as it appears to be present largely in the inactive form.
J. R. Newton - One of the best experts on this subject based on the ideXlab platform.
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decision tree analysis of clinical data to aid diagnostic reasoning for equine Laminitis a cross sectional study
Veterinary Record, 2016Co-Authors: C. E. Wylie, K. L.p. Verheyen, Darren J Shaw, J. R. NewtonAbstract:The objective of this cross-sectional study was to compare the prevalence of selected clinical signs in Laminitis cases and non-laminitic but lame controls to evaluate their capability to discriminate Laminitis from other causes of lameness. Participating veterinary practitioners completed a checklist of Laminitis-associated clinical signs identified by literature review. Cases were defined as horses/ponies with veterinary-diagnosed, clinically apparent Laminitis; controls were horses/ponies with any lameness other than Laminitis. Associations were tested by logistic regression with adjusted odds ratios (ORs) and 95% confidence intervals, with veterinary practice as an a priori fixed effect. Multivariable analysis using graphical classification tree-based statistical models linked Laminitis prevalence with specific combinations of clinical signs. Data were collected for 588 cases and 201 controls. Five clinical signs had a difference in prevalence of greater than +50 per cent: ‘reluctance to walk’ (OR 4.4), ‘short, stilted gait at walk’ (OR 9.4), ‘difficulty turning’ (OR 16.9), ‘shifting weight’ (OR 17.7) and ‘increased digital pulse’ (OR 13.2) (all P
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a cohort study of equine Laminitis in great britain 2009 2011 estimation of disease frequency and description of clinical signs in 577 cases
Equine Veterinary Journal, 2013Co-Authors: C. E. Wylie, K. L.p. Verheyen, S N Collins, J. R. NewtonAbstract:Reasons for performing study: A previous systematic review highlighted a lack of good evidence regarding the frequency of equine Laminitis in Great Britain. Objectives: To estimate the frequency of veterinary-diagnosed active Laminitis in the general horse population of Great Britain and to describe the clinical signs present in cases. Study design: Prospective cohort study. Methods: Data on active episodes of equine Laminitis were collected from veterinary practitioners. Results: The prevalence of veterinary-diagnosed active Laminitis was 0.47% (95% confidence interval [CI] 0.42-0.52%) for the veterinary-attended population and 0.49% (95% CI 0.43-0.55%) for the veterinary-registered population, suggesting that active episodes of Laminitis accounted for nearly one in 200 equine visits and occurred in nearly one in 200 horses registered with veterinary practices. The incidence of veterinary-diagnosed active Laminitis was 0.5 cases per 100 horse-years at risk (95% CI 0.44-0.57). Laminitis occurred in all limbs, but most commonly affected the forelimbs bilaterally (53.5%, 95% CI 49.4-57.7%) and was most severe in the front feet. The most common clinical signs were increased digital pulses, difficulty turning and a short, stilted gait at walk. Conclusions and potential relevance: The frequency of veterinary-diagnosed active Laminitis was considerably lower than previously published estimates, which is probably due to differences in geographical setting, study period, case definition, study design and study populations.
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A cohort study of equine Laminitis in Great Britain 2009-2011: Estimation of disease frequency and description of clinical signs in 577 cases
Equine Veterinary Journal, 2013Co-Authors: C. E. Wylie, K. L.p. Verheyen, S N Collins, J. R. NewtonAbstract:REASONS FOR PERFORMING STUDY: A previous systematic review highlighted a lack of good evidence regarding the frequency of equine Laminitis in Great Britain.\n\nOBJECTIVES: To estimate the frequency of veterinary-diagnosed active Laminitis in the general horse population of Great Britain and to describe the clinical signs present in cases.\n\nSTUDY DESIGN: Prospective cohort study.\n\nMETHODS: Data on active episodes of equine Laminitis were collected from veterinary practitioners.\n\nRESULTS: The prevalence of veterinary-diagnosed active Laminitis was 0.47% (95% confidence interval [CI] 0.42-0.52%) for the veterinary-attended population and 0.49% (95% CI 0.43-0.55%) for the veterinary-registered population, suggesting that active episodes of Laminitis accounted for nearly one in 200 equine visits and occurred in nearly one in 200 horses registered with veterinary practices. The incidence of veterinary-diagnosed active Laminitis was 0.5 cases per 100 horse-years at risk (95% CI 0.44-0.57). Laminitis occurred in all limbs, but most commonly affected the forelimbs bilaterally (53.5%, 95% CI 49.4-57.7%) and was most severe in the front feet. The most common clinical signs were increased digital pulses, difficulty turning and a short, stilted gait at walk.\n\nCONCLUSIONS AND POTENTIAL RELEVANCE: The frequency of veterinary-diagnosed active Laminitis was considerably lower than previously published estimates, which is probably due to differences in geographical setting, study period, case definition, study design and study populations.
C. E. Wylie - One of the best experts on this subject based on the ideXlab platform.
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decision tree analysis of clinical data to aid diagnostic reasoning for equine Laminitis a cross sectional study
Veterinary Record, 2016Co-Authors: C. E. Wylie, K. L.p. Verheyen, Darren J Shaw, J. R. NewtonAbstract:The objective of this cross-sectional study was to compare the prevalence of selected clinical signs in Laminitis cases and non-laminitic but lame controls to evaluate their capability to discriminate Laminitis from other causes of lameness. Participating veterinary practitioners completed a checklist of Laminitis-associated clinical signs identified by literature review. Cases were defined as horses/ponies with veterinary-diagnosed, clinically apparent Laminitis; controls were horses/ponies with any lameness other than Laminitis. Associations were tested by logistic regression with adjusted odds ratios (ORs) and 95% confidence intervals, with veterinary practice as an a priori fixed effect. Multivariable analysis using graphical classification tree-based statistical models linked Laminitis prevalence with specific combinations of clinical signs. Data were collected for 588 cases and 201 controls. Five clinical signs had a difference in prevalence of greater than +50 per cent: ‘reluctance to walk’ (OR 4.4), ‘short, stilted gait at walk’ (OR 9.4), ‘difficulty turning’ (OR 16.9), ‘shifting weight’ (OR 17.7) and ‘increased digital pulse’ (OR 13.2) (all P
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a cohort study of equine Laminitis in great britain 2009 2011 estimation of disease frequency and description of clinical signs in 577 cases
Equine Veterinary Journal, 2013Co-Authors: C. E. Wylie, K. L.p. Verheyen, S N Collins, J. R. NewtonAbstract:Reasons for performing study: A previous systematic review highlighted a lack of good evidence regarding the frequency of equine Laminitis in Great Britain. Objectives: To estimate the frequency of veterinary-diagnosed active Laminitis in the general horse population of Great Britain and to describe the clinical signs present in cases. Study design: Prospective cohort study. Methods: Data on active episodes of equine Laminitis were collected from veterinary practitioners. Results: The prevalence of veterinary-diagnosed active Laminitis was 0.47% (95% confidence interval [CI] 0.42-0.52%) for the veterinary-attended population and 0.49% (95% CI 0.43-0.55%) for the veterinary-registered population, suggesting that active episodes of Laminitis accounted for nearly one in 200 equine visits and occurred in nearly one in 200 horses registered with veterinary practices. The incidence of veterinary-diagnosed active Laminitis was 0.5 cases per 100 horse-years at risk (95% CI 0.44-0.57). Laminitis occurred in all limbs, but most commonly affected the forelimbs bilaterally (53.5%, 95% CI 49.4-57.7%) and was most severe in the front feet. The most common clinical signs were increased digital pulses, difficulty turning and a short, stilted gait at walk. Conclusions and potential relevance: The frequency of veterinary-diagnosed active Laminitis was considerably lower than previously published estimates, which is probably due to differences in geographical setting, study period, case definition, study design and study populations.
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risk factors for equine Laminitis a case control study conducted in veterinary registered horses and ponies in great britain between 2009 and 2011
Veterinary Journal, 2013Co-Authors: C. E. Wylie, K. L.p. Verheyen, S N Collins, Richard J NewtonAbstract:Laminitis is a highly debilitating disease of the foot known to have a complex and multifactorial aetiology of metabolic, inflammatory, traumatic or vascular origin. The disease has major welfare implications due to unrelenting pain associated with degenerative changes, which often necessitate euthanasia on welfare grounds. Despite this, there have been few high-quality studies investigating risk factors for equine Laminitis, and only a limited number of risk factors have been previously investigated. The aim of this study was to conduct a case-control study of risk factors for active episodes of veterinary-diagnosed Laminitis in horses and ponies attended by veterinary practitioners in Great Britain, based on multivariable statistical analyses. Questionnaires were received for 1010 animals, comprising 191 Laminitis cases and 819 controls. Factors associated with an increased risk of Laminitis were weight gain in the previous 3. months, summer and winter months compared to spring, new access to grass in the previous 4. weeks, box rest in the previous week, owner-reported history of Laminitis, lameness or foot-soreness after shoeing/trimming, existing endocrinopathic (pituitary pars intermedia dysfunction and equine metabolic syndrome) disease and increasing time since the last anthelmintic treatment. Factors associated with a decreased risk of Laminitis were increasing height (cm), feeding of additional supplements in the previous week and transportation in the previous week. Novel associated factors were identified that may aid in the management and prevention of the disease in the veterinary-registered equine population.
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A cohort study of equine Laminitis in Great Britain 2009-2011: Estimation of disease frequency and description of clinical signs in 577 cases
Equine Veterinary Journal, 2013Co-Authors: C. E. Wylie, K. L.p. Verheyen, S N Collins, J. R. NewtonAbstract:REASONS FOR PERFORMING STUDY: A previous systematic review highlighted a lack of good evidence regarding the frequency of equine Laminitis in Great Britain.\n\nOBJECTIVES: To estimate the frequency of veterinary-diagnosed active Laminitis in the general horse population of Great Britain and to describe the clinical signs present in cases.\n\nSTUDY DESIGN: Prospective cohort study.\n\nMETHODS: Data on active episodes of equine Laminitis were collected from veterinary practitioners.\n\nRESULTS: The prevalence of veterinary-diagnosed active Laminitis was 0.47% (95% confidence interval [CI] 0.42-0.52%) for the veterinary-attended population and 0.49% (95% CI 0.43-0.55%) for the veterinary-registered population, suggesting that active episodes of Laminitis accounted for nearly one in 200 equine visits and occurred in nearly one in 200 horses registered with veterinary practices. The incidence of veterinary-diagnosed active Laminitis was 0.5 cases per 100 horse-years at risk (95% CI 0.44-0.57). Laminitis occurred in all limbs, but most commonly affected the forelimbs bilaterally (53.5%, 95% CI 49.4-57.7%) and was most severe in the front feet. The most common clinical signs were increased digital pulses, difficulty turning and a short, stilted gait at walk.\n\nCONCLUSIONS AND POTENTIAL RELEVANCE: The frequency of veterinary-diagnosed active Laminitis was considerably lower than previously published estimates, which is probably due to differences in geographical setting, study period, case definition, study design and study populations.
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frequency of equine Laminitis a systematic review with quality appraisal of published evidence
Veterinary Journal, 2011Co-Authors: C. E. Wylie, K. L.p. Verheyen, S N Collins, Richard J NewtonAbstract:Abstract Equine Laminitis is a highly debilitating disease of the foot. Despite its perceived importance, epidemiological characteristics are poorly understood and the true frequency of the disease remains unclear. The objective of this study was to retrospectively assess previous research to identify publications which provide the best evidence of the frequency of naturally-occurring equine Laminitis. A systematic review of English language publications was conducted using MEDLINE (1950–2010), CAB Direct (1910–2010) and IVIS (1997–2010). Additional publications were included by searching bibliographies. Search terms included Laminitis, equine, frequency, prevalence and incidence. Studies that allowed frequency estimations to be made for naturally-occurring equine Laminitis were included. Information was extracted using predefined data fields, including 13 study quality indicators. Sixty-nine publications were appraised. Ten were considered to provide the most reliable information, estimating the frequency of equine Laminitis ranging from 1.5% to 34%. Previous publications estimating Laminitis frequency were generally poor quality. Laminitis frequency varied across publications however the publications included in this review focussed on many of the different underlying Laminitis aetiologies and comparison of the frequencies between groups would be inappropriate. High-quality evidence-based studies are needed to estimate the true disease frequency in different equine populations.
M. N. Sillence - One of the best experts on this subject based on the ideXlab platform.
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Incidence and risk factors for recurrence of endocrinopathic Laminitis in horses
Journal of Veterinary Internal Medicine, 2019Co-Authors: M. A. De Laat, M. N. Sillence, Dania Reiche, James McgreeAbstract:BACKGROUND: Endocrinopathic Laminitis is common in horses and ponies, but the recurrence rate of the disease is poorly defined. OBJECTIVES: To determine the incidence of, and risk factors for, the recurrence of endocrinopathic Laminitis. ANIMALS: Privately owned horses and ponies with acute Laminitis (n = 317, of which 276 cases with endocrinopathic Laminitis were followed up to study completion). METHODS: This prospective cohort study collected data on veterinary‐diagnosed cases of acute Laminitis for 2 years. Each case was classified on acceptance to the study as endocrinopathic or non‐endocrinopathic using data collected in a questionnaire completed by the animal's veterinarian. Follow‐up data were collected at regular intervals to determine whether the Laminitis recurred in the 2‐year period after diagnosis. RESULTS: The recurrence rate for endocrinopathic Laminitis was 34.1%. The risk of recurrence during the 2‐year study period increased with basal, fasted serum insulin concentration (P ≤ .05), with the probability of recurrence increasing markedly as the insulin concentration increased beyond the normal range (0‐20 μIU/mL) to over the threshold for normal (up to approximately 45 μIU/mL). Being previously diagnosed with Laminitis (before the study; P = .05) was also a risk factor for recurrent Laminitis. Cases with a higher Obel grade of Laminitis were likely (P = .05) to recur sooner. CONCLUSIONS AND CLINICAL IMPORTANCE: Knowing that hyperinsulinemia and being previously diagnosed with Laminitis are significant risk factors for recurrence will enable clinicians to proactively address these factors, thereby potentially reducing the risk of recurrence of Laminitis.
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the oral glucose test predicts Laminitis risk in ponies fed a diet high in nonstructural carbohydrates
Domestic Animal Endocrinology, 2018Co-Authors: Alexandra Meier, M. A. De Laat, C. C. Pollitt, James Mcgree, Dania Birte Reiche, Donald M Walsh, M. N. SillenceAbstract:The aim of this study was to investigate the relationship between Laminitis development in ponies and insulin/glucose concentrations in response to the oral glucose test (OGT) and a dietary challenge high in nonstructural carbohydrates (NSCs). After undergoing an OGT (1 g dextrose/kg BW in feed), 37 ponies with 2-h serum insulin concentrations ranging from 22 to 1,133 μIU/mL were subjected to a diet challenge period (DCP), consuming 12 g NSC/kg BW/d for up to 18 d. Insulin and glucose responses were measured on day 2 of the DCP. Clinical Laminitis was diagnosed by blinded experts and confirmed radiographically. Basal ACTH levels and clinical signs were assessed to investigate concurrent putative pituitary pars intermedia dysfunction (PPID). The diet induced Obel grade 1 or 2 Laminitis in 14 ponies (38%). The ponies that developed Laminitis had higher maximum concentrations of blood glucose (P = 0.04) and serum insulin (P = 0.02) in response to the diet. The geometric mean (95% CI) blood glucose concentration for Laminitis cases was 14.9 (12.9-17.2) mM, compared to 10.7 (9.2-12.5) mM for ponies who did not develop Laminitis. Similarly, the geometric mean (95% CI) for serum insulin was 396 (301-520) μIU/mL for Laminitis cases, compared to 216 (148-316) μIU/mL for ponies who did not develop Laminitis. Laminitis incidence was likewise associated with insulin concentrations measured during the OGT. Laminitis occurred at frequencies of 0% (0/7) if postdextrose insulin (μIU/mL) was 195 μIU/mL. Basal ACTH concentrations were above seasonally accepted reference ranges in 16/37 ponies, and 8 of these animals (50%) developed Laminitis. This included all 5 ponies in the study that had clinical signs of PPID (100%). In contrast, hyperinsulinemia and Laminitis occurred in only 3/11 ponies (27%) with elevated ACTH concentrations and no clinical signs of PPID (P = 0.009). Thus, Laminitis occurrence was associated with higher glucose and insulin responses to both the OGT and challenge diet, and the frequency of Laminitis can be predicted based on insulin and glucose hyperresponsiveness to these oral carbohydrate challenges.
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equine Laminitis comparative histopathology 48 hours after experimental induction with insulin or alimentary oligofructose in standardbred horses
Journal of Comparative Pathology, 2011Co-Authors: M. A. De Laat, C. M. Mcgowan, M. N. Sillence, C. C. PollittAbstract:Summary Laminitis has many triggers and comparing the histopathology of lesions induced by different causes may help to establish whether a common mechanism or multiple pathologies are involved. The aim of this study was to describe the microscopical lesions and to quantify morphometric changes in the lamellae of horses with insulin-induced (n = 4) and oligofructose (OF)-induced Laminitis (n = 4) compared with normal controls (n = 4). Archived lamellar samples collected during two previous studies were used. Laminitis was induced within 48 h in standardbred horses with either a euglycaemic, hyperinsulinaemic clamp (EHC) technique or, in a separate experiment, with an overdose of alimentary OF. Normal tissue was obtained from control horses in the EHC experiment that received a balanced electrolyte solution intravenously for 48 h. Six measurements of lamellar length and width were recorded for each hoof. Leucocyte infiltration was assessed by immunolocalization of calprotectin. All control horses exhibited normal lamellar architecture, whereas treated horses developed clinical and histopathological changes consistent with Laminitis. Laminitic samples displayed lengthening and narrowing of secondary epidermal lamellae (SELs), rounded epidermal basal cell (EBC) nuclei, mitosis and apoptosis. In the fore feet of laminitic horses, the length from the end of the keratinized axis to the axial tip of the primary epidermal lamellae (PELs) was increased (P
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the developmental and acute phases of insulin induced Laminitis involve minimal metalloproteinase activity
Veterinary Immunology and Immunopathology, 2011Co-Authors: M. A. De Laat, C. M. Mcgowan, M. N. Sillence, M T Kyawtanner, A R Nourian, C. C. PollittAbstract:Metalloproteinases have been implicated in the pathogenesis of equine Laminitis and other inflammatory conditions, through their role in the degradation and remodelling of the extracellular matrix environment. Matrix metalloproteinases (MMPs) and their inhibitors are present in normal equine lamellae, with increased secretion and activation of some metalloproteinases reported in horses with Laminitis associated with systemic inflammation. It is unknown whether these enzymes are involved in insulin-induced Laminitis, which occurs without overt systemic inflammation. In this study, gene expression of MMP-2, MMP-9, MT1-MMP, ADAMTS-4 and TIMP-3 was determined in the lamellar tissue of normal control horses (n = 4) and horses that developed Laminitis after 48 h of induced hyperinsulinaemia (n = 4), using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Protein concentrations of MMP-2 and MMP-9 were also examined using gelatin zymography in horses subject to prolonged hyperinsulinaemia for 6 h (n = 4), 12 h (n = 4), 24 h (n = 4) and 48 h (n = 4), and in normal control horses (n = 4). The only change in gene expression observed was an upregulation of MMP-9 (p < 0.05) in horses that developed insulin-induced Laminitis (48 h). Zymographical analysis showed an increase (p < 0.05) in pro MMP-9 during the acute phase of Laminitis (48 h), whereas pro MMP-2 was present in similar concentration in the tissue of all horses. Thus, MMP-2, MT1-MMP, TIMP-3 and ADAMTS-4 do not appear to play a significant role in the pathogenesis of insulin-induced Laminitis. The increased expression of MMP-9 may be associated with the infiltration of inflammatory leukocytes, or may be a direct result of hyperinsulinaemia. The exact role of MMP-9 in basement membrane degradation in Laminitis is uncertain as it appears to be present largely in the inactive form.
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histopathology of insulin induced Laminitis in ponies
Equine Veterinary Journal, 2010Co-Authors: K E Asplin, M. N. Sillence, C. C. Pollitt, J C Pattersonkane, C. M. McgowanAbstract:Reasons for performing study: Ponies with Laminitis associatedwith insulin resistance and hyperinsulinaemia lack systemicand/or intestinal inflammatory signs, suggesting a differentpathogenesis potentially reflected in differing histopathology.Objectives: To describe the histological appearance andquantify morphological changes in primary and secondaryepidermal lamellae (PEL and SEL) of Laminitis lesions fromponies with insulin-induced Laminitis.Methods: Equine hoof lamellar tissue was obtained from 4control ponies and 5 ponies with Laminitis induced followinginfusion of insulin (1036 ± 55 mU/ml) while maintainingeuglycaemia for 55.4 ± 5.5 h. Sections from all 4 hooves werestained and examined by a veterinary pathologist.Measurements of lamellar length (PEL and SEL) were madein mid-dorsal sections of the right forefeet by 2 blindedobservers. Immunolabelling for calprotectin was performedusing a monoclonal antibody.Results: No lesions were detected in normal ponies. Lesionsdetected in ponies with Laminitis were variable in severitybetween ponies.Within ponies, SEL lesions were more severealong the axial region of PEL. Lesions included swelling,disorganisation and abnormal keratinisation of epidermalcells, increased mitotic activity and apoptosis. Separation ofbasement membranes wasminimal. Immunostaining revealedinflammatory cells within the lamellar dermis. SEL weresignificantly elongated in laminitic hooves relative to controls,with the greatest elongation in those attached to abaxial andmiddle regions of PEL.Conclusions: Laminitis induced by prolonged infusion of insulinlacked widespread basement membrane disintegration, andincreases in epidermal cellular proliferation at axial aspectswere marked for this acute stage of disease.Potential releVance: Defining equine Laminitis entirely interms of separation of the basement membrane may not beappropriate for Laminitis associated with hyperinsulinaemia.
