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Gastric Ulceration - Horse (view source)

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→‎Extrinsic ulcerogenic factors (RISK FACTORS)

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====Extrinsic ulcerogenic factors (RISK FACTORS)====

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*'''Exercise:''' ~~There~~ appears to be a high prevalence of gastric ulcers in horses performing in most disciplines.<ref>Hartmann, A.M, Frankeny, R.L (2003) A preliminary investigation into the association between competition and gastric ulcer formation in non-racing performance horses. ''J Equine Vet Sci'', 23:560-561. In: Nadeau, J.A, Andrews, F.M (2009) ''Science: Overviews'' Equine gastric ulcer syndrome: The continuing conundrum. ''Equine Vet J'', 41(7):611-615.</ref> Although this may be related to exercise, other confounding factors related to these disciplines such as travel, diet, feeding regime, use of non-steroidal anti-inflammatories (NSAIDs) and stress may be significant. However, Vatistas and co-workers (1999) were able to induce and maintain EGUS in racehorses in fast work without the use of NSAIDs or fasting before exercise.<ref name="Vatistas 2">Vatistas, N.J, Sifferman, R.L, Holste, J, Cox, J.L, Pinalto, G, Schultz, K.T (1999) Induction and maintenance of gastric ulceration in horses in simulated race training. ''Equine Vet J Suppl'', 29:40-44</ref> There is also evidence that training for just 8 days is suffcient to induce gastric ulcers.<ref>White, G, McClure, S.R, Siifferman, R, Holste, J.E, Fleishman, C, Murray, M.J, Cramer, L.G (2007) Effects of short-term light to heavy exercise on gastric ulcer development in horses and efficacy of omeprazole paste in preventing gastric ulceration. ''J Am Vet Med Assoc'', 230(11):1680-2.</ref> The higher prevalence of gastric ulcers at ''post mortem'' in racehorses in training compared to those in retirement is consistent with the hypothesis that exercise may be an important risk factor for EGUS.<ref name="Hammond">Hammond, C.J, Mason, D.K, Watkins, K.L (1986) Gastric ulceration in mature Thoroughbred horses. ''Equine Vet J'', 18(4):284-287.</ref> Strenuous exercise is known to stimulate gastrin release which has effects on HCl secretion, gastric emptying and gastric blood flow. Diversion of blood to active muscle groups may further deprive the gastric mucosa of the perfusion required for its integrity(REF). It is also thought that exposure of the squamous mucosa to acid is increased as the stomach is compressed by the abdominal viscera and diaphragm during excercise.<ref>Lorenzo-Figueras, M, Merritt, A.M (2002) Effects of exercise on gastric volume and pH in the proximal portion of the stomach of horses. ''Am J Vet Res'', 63:1481-1487.</ref>

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*'''Exercise:''' there appears to be a high prevalence of gastric ulcers in horses performing in most disciplines.<ref>Hartmann, A.M, Frankeny, R.L (2003) A preliminary investigation into the association between competition and gastric ulcer formation in non-racing performance horses. ''J Equine Vet Sci'', 23:560-561. In: Nadeau, J.A, Andrews, F.M (2009) ''Science: Overviews'' Equine gastric ulcer syndrome: The continuing conundrum. ''Equine Vet J'', 41(7):611-615.</ref> Although this may be related to exercise, other confounding factors related to these disciplines such as travel, diet, feeding regime, use of non-steroidal anti-inflammatories (NSAIDs) and stress may be significant. However, Vatistas and co-workers (1999) were able to induce and maintain EGUS in racehorses in fast work without the use of NSAIDs or fasting before exercise.<ref name="Vatistas 2">Vatistas, N.J, Sifferman, R.L, Holste, J, Cox, J.L, Pinalto, G, Schultz, K.T (1999) Induction and maintenance of gastric ulceration in horses in simulated race training. ''Equine Vet J Suppl'', 29:40-44</ref> There is also evidence that training for just 8 days is suffcient to induce gastric ulcers.<ref>White, G, McClure, S.R, Siifferman, R, Holste, J.E, Fleishman, C, Murray, M.J, Cramer, L.G (2007) Effects of short-term light to heavy exercise on gastric ulcer development in horses and efficacy of omeprazole paste in preventing gastric ulceration. ''J Am Vet Med Assoc'', 230(11):1680-2.</ref> The higher prevalence of gastric ulcers at ''post mortem'' in racehorses in training compared to those in retirement is consistent with the hypothesis that exercise may be an important risk factor for EGUS.<ref name="Hammond">Hammond, C.J, Mason, D.K, Watkins, K.L (1986) Gastric ulceration in mature Thoroughbred horses. ''Equine Vet J'', 18(4):284-287.</ref> Strenuous exercise is known to stimulate gastrin release which has effects on HCl secretion, gastric emptying and gastric blood flow. Diversion of blood to active muscle groups may further deprive the gastric mucosa of the perfusion required for its integrity(REF). It is also thought that exposure of the squamous mucosa to acid is increased as the stomach is compressed by the abdominal viscera and diaphragm during excercise.<ref>Lorenzo-Figueras, M, Merritt, A.M (2002) Effects of exercise on gastric volume and pH in the proximal portion of the stomach of horses. ''Am J Vet Res'', 63:1481-1487.</ref>

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*'''Housing and Transport:''' ~~Housing~~ in '''stables''' has been proposed as a risk factor for gastric ulcers, with more lesions being found in confined horses compared to those out at grass.<ref>Murray, M.J, Eichorn, E.S (1996) Effects of intermittent feed deprivation, intermittent feed deprivation with ranitidine administration, and stall

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*'''Housing and Transport:''' housing in '''stables''' has been proposed as a risk factor for gastric ulcers, with more lesions being found in confined horses compared to those out at grass.<ref>Murray, M.J, Eichorn, E.S (1996) Effects of intermittent feed deprivation, intermittent feed deprivation with ranitidine administration, and stall

confinement with ''ad libitum'' access to hay on gastric ulceration in horses. ''Am J Vet Res'', 57:1599-1603.</ref> However, when comparing solitary stable confinement with stabling next to a companion, and finally turn out in a paddock, Husted and colleagues (2008) found that the environmental situation had no effect on mucosal acid exposure in the equine stomach.<ref>Husted, L, Sanchex, L.C, Olsen, S.N, Baptiste, K.E, Merritt, A.M (2008) Effect of paddock vs. stall housing on 24 hour gastric pH within the proximal and ventral equine stomach. ''Equine Vet J'', 40(4):337-41.</ref> Thus the reason for a higher prevalence of EGUS in stabled animals is unclear. '''Transport''' has also been shown to induce squamous mucosal ulceration in horses, by as yet, unidentified mechanisms.<ref>McClure, S.R, Carithers, D.S, Gross, S.J, Murray, M.J (2005) Gastric ulcer development in horses in a simulated show or training environment. ''J Am Vet Med Assoc'', 227:775-777.</ref>

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*'''Diet and feeding regime:''' ~~'''Feed~~ deprivation~~'''~~ encourages gastric ulceration in three ways: (1) it precludes the buffering capacity of protein leading to a reduced gastric pH,<ref>Murray, M.J, Schusser, G.F (1993) Measurement of 24-h gastric pH using an indwelling pH electrode in horses unfed, fed and treated with ranitidine. ''Equine Vet J'', 25:417-421. In: Sandin, A, Skidell, J, Haggstrom, J, Nilsson, G (2000) ''Postmortem'' findings of gastric ulcers in Swedish horses older than age one year: a retrospective study of 3715 horses (1924–1996). ''Equine Vet J'', 32(1):36-42.</ref> (2) it empties the stomach and exposes the squamous mucosa to the more mobile gastric juice<ref name="Sandin">Sandin, A, Skidell, J, Haggstrom, J, Nilsson, G (2000) ''Postmortem'' findings of gastric ulcers in Swedish horses older than age one year: a retrospective study of 3715 horses (1924–1996). ''Equine Vet J'', 32(1):36-42.</ref> and (3) it permits the accumulation of bile salts, which, together with HCl, cause greater squamous mucosal damage than HCl alone.<ref>Berschneider, H.M, Blikslager, A.T, Roberts, M.C (1999) Role of dudodenal relfux in nonglandular gastric ulcer disease of the mature horse. ''Equine Vet J Suppl'', 29:24-29.</ref> It is unsurprising, therefore, that an alternating feed-fast protocol would produce a consistent model of ulcer induction in the equine squamous mucosa.<ref>Murray, M.J, Schusser, G.F (1993) Measurement of 24-h gastric pH using an indwelling pH electrode in horses unfed, fed and treated with ranitidine. ''Equine Vet J'', 25:417-421. In: Sanchez, L.C (2010) 'Diseases Of The Stomach' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), Saunders, Chapter 15.</ref><ref>Murray, M.J (1994) Equine model of inducing ulceration in alimentary squamous epithelial mucosa. ''Dig Dis Sci'', 39:2530-2535. In: Sanchez, L.C (2010) 'Diseases Of The Stomach' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), Saunders, Chapter 15.</ref> Despite this, feed deprivation is not a prerequisite for gastric ulceration in the horse.<ref name="Vatistas thesis">Vatistas, N.J (1998) Gastric Ulceration in the Racing Thoroughbred. ''PhD Thesis''. In: Vatistas, N.J, Sifferman, R.L, Holste, J, Cox, J.L, Pinalto, G, Schultz, K.T (1999) Induction and maintenance of gastric ulceration in horses in simulated race training. ''Equine Vet J Suppl'', 29:40-44</ref> Diets that are plentiful in roughage prolong the mastication process and the production of salivary bicarbonate that protects the gastric mucosa. A diet of '''high grain and low roughage''' thus predisposes to EGUS.<ref name="Nadeau"> In: Nadeau, J.A, Andrews, F.M (2009) ''Science: Overviews'' Equine gastric ulcer syndrome: The continuing conundrum. ''Equine Vet J'', 41(7):611-615.</ref> This sort of diet is commonly fed to racehorses but dietary components have also been shown to influence EGUS risk in nonracehorses.<ref>Luthersson, N, Nielson, K.H, Harris, P, Parkin, T.D (2009) Risk factors associated with equine gastric ulceration syndrome (EGUS) in 201 horses in Denmark. ''Equine Vet J'', 41(7):625-30.</ref> Ponies fed a '''concentrate diet''' had a greater prevalence of gastric ulcers than ponies fed hay alone.<ref name="Vatistas 2">Vatistas, N.J, Sifferman, R.L, Holste, J, Cox, J.L, Pinalto, G, Schultz, K.T (1999) Induction and maintenance of gastric ulceration in horses in simulated race training. ''Equine Vet J Suppl'', 29:40-44</ref> and this may be because grain and pelleted feeds are asssociated with increased serum gastrin.<ref>Smyth, G.B, Young, D.W, Hammond, L.S (1988) Effects of diet and feeding on post-prandial serum gastrin and insulin concentrations in adult horses. ''Equine Vet J Suppl'' 7:56-59.</ref> '''High starch meals''' are also a risk because they are fermented to VFAs and lactic acid and are emptied from the stomach relatively slowly.<ref>Mètayer, N, Lhôte, M, Bahr, A, Cohen, N.D, Kim, I, Rousell, A.J, Julliand, V (2004) Meal size and starch content affect gastric emptying in horses. ''Equine Vet J'', 36:434-440. In: Nadeau, J.A, Andrews, F.M (2009) ''Science: Overviews'' Equine gastric ulcer syndrome: The continuing conundrum. ''Equine Vet J'', 41(7):611-615.</ref><ref>Taharaguchi, S, Okai, K, Orita, Y, Kuwano, M, Ueno, T, Taniyama, H (2004) Relation between amounts of concentrated feed given mares and gastric ulcers in foals. ''J Japan Vet Med Ass'', 57:366-370. In: Nadeau, J.A, Andrews, F.M (2009) ''Science: Overviews'' Equine gastric ulcer syndrome: The continuing conundrum. ''Equine Vet J'', 41(7):611-615.</ref><ref>Boswinkel, A.M, Ellis, A.D, Sloet van Oldruitenborgh-Oosterbaan, M.M (2007) The influence of low versus high fibre haylage diets in combination with training or pasture rest on equine gastric ulceration syndrome (EGUS). ''Pferdeheilkunde'', 23:123-130. In: Nadeau, J.A, Andrews, F.M (2009) ''Science: Overviews'' Equine gastric ulcer syndrome: The continuing conundrum. ''Equine Vet J'', 41(7):611-615.</ref>

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*'''Diet and feeding regime:''' feed deprivation encourages gastric ulceration in three ways: (1) it precludes the buffering capacity of protein leading to a reduced gastric pH,<ref>Murray, M.J, Schusser, G.F (1993) Measurement of 24-h gastric pH using an indwelling pH electrode in horses unfed, fed and treated with ranitidine. ''Equine Vet J'', 25:417-421. In: Sandin, A, Skidell, J, Haggstrom, J, Nilsson, G (2000) ''Postmortem'' findings of gastric ulcers in Swedish horses older than age one year: a retrospective study of 3715 horses (1924–1996). ''Equine Vet J'', 32(1):36-42.</ref> (2) it empties the stomach and exposes the squamous mucosa to the more mobile gastric juice<ref name="Sandin">Sandin, A, Skidell, J, Haggstrom, J, Nilsson, G (2000) ''Postmortem'' findings of gastric ulcers in Swedish horses older than age one year: a retrospective study of 3715 horses (1924–1996). ''Equine Vet J'', 32(1):36-42.</ref> and (3) it permits the accumulation of bile salts, which, together with HCl, cause greater squamous mucosal damage than HCl alone.<ref>Berschneider, H.M, Blikslager, A.T, Roberts, M.C (1999) Role of dudodenal relfux in nonglandular gastric ulcer disease of the mature horse. ''Equine Vet J Suppl'', 29:24-29.</ref> It is unsurprising, therefore, that an alternating feed-fast protocol would produce a consistent model of ulcer induction in the equine squamous mucosa.<ref>Murray, M.J, Schusser, G.F (1993) Measurement of 24-h gastric pH using an indwelling pH electrode in horses unfed, fed and treated with ranitidine. ''Equine Vet J'', 25:417-421. In: Sanchez, L.C (2010) 'Diseases Of The Stomach' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), Saunders, Chapter 15.</ref><ref>Murray, M.J (1994) Equine model of inducing ulceration in alimentary squamous epithelial mucosa. ''Dig Dis Sci'', 39:2530-2535. In: Sanchez, L.C (2010) 'Diseases Of The Stomach' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), Saunders, Chapter 15.</ref> Despite this, feed deprivation is not a prerequisite for gastric ulceration in the horse.<ref name="Vatistas thesis">Vatistas, N.J (1998) Gastric Ulceration in the Racing Thoroughbred. ''PhD Thesis''. In: Vatistas, N.J, Sifferman, R.L, Holste, J, Cox, J.L, Pinalto, G, Schultz, K.T (1999) Induction and maintenance of gastric ulceration in horses in simulated race training. ''Equine Vet J Suppl'', 29:40-44</ref> Diets that are plentiful in roughage prolong the mastication process and the production of salivary bicarbonate that protects the gastric mucosa. A diet of '''high grain and low roughage''' thus predisposes to EGUS.<ref name="Nadeau"> In: Nadeau, J.A, Andrews, F.M (2009) ''Science: Overviews'' Equine gastric ulcer syndrome: The continuing conundrum. ''Equine Vet J'', 41(7):611-615.</ref> This sort of diet is commonly fed to racehorses but dietary components have also been shown to influence EGUS risk in nonracehorses.<ref>Luthersson, N, Nielson, K.H, Harris, P, Parkin, T.D (2009) Risk factors associated with equine gastric ulceration syndrome (EGUS) in 201 horses in Denmark. ''Equine Vet J'', 41(7):625-30.</ref> Ponies fed a '''concentrate diet''' had a greater prevalence of gastric ulcers than ponies fed hay alone<ref name="Vatistas 2">Vatistas, N.J, Sifferman, R.L, Holste, J, Cox, J.L, Pinalto, G, Schultz, K.T (1999) Induction and maintenance of gastric ulceration in horses in simulated race training. ''Equine Vet J Suppl'', 29:40-44</ref> and this may be because grain and pelleted feeds are asssociated with increased serum gastrin.<ref>Smyth, G.B, Young, D.W, Hammond, L.S (1988) Effects of diet and feeding on post-prandial serum gastrin and insulin concentrations in adult horses. ''Equine Vet J Suppl'' 7:56-59.</ref> '''High starch meals''' are also a risk because they are fermented to VFAs and lactic acid and are emptied from the stomach relatively slowly.<ref>Mètayer, N, Lhôte, M, Bahr, A, Cohen, N.D, Kim, I, Rousell, A.J, Julliand, V (2004) Meal size and starch content affect gastric emptying in horses. ''Equine Vet J'', 36:434-440. In: Nadeau, J.A, Andrews, F.M (2009) ''Science: Overviews'' Equine gastric ulcer syndrome: The continuing conundrum. ''Equine Vet J'', 41(7):611-615.</ref><ref>Taharaguchi, S, Okai, K, Orita, Y, Kuwano, M, Ueno, T, Taniyama, H (2004) Relation between amounts of concentrated feed given mares and gastric ulcers in foals. ''J Japan Vet Med Ass'', 57:366-370. In: Nadeau, J.A, Andrews, F.M (2009) ''Science: Overviews'' Equine gastric ulcer syndrome: The continuing conundrum. ''Equine Vet J'', 41(7):611-615.</ref><ref>Boswinkel, A.M, Ellis, A.D, Sloet van Oldruitenborgh-Oosterbaan, M.M (2007) The influence of low versus high fibre haylage diets in combination with training or pasture rest on equine gastric ulceration syndrome (EGUS). ''Pferdeheilkunde'', 23:123-130. In: Nadeau, J.A, Andrews, F.M (2009) ''Science: Overviews'' Equine gastric ulcer syndrome: The continuing conundrum. ''Equine Vet J'', 41(7):611-615.</ref>

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*'''Other ailments:''' ~~Conditions~~ that produce abdominal pain and/or inappetance are likely to reduce food intake and predipose to gastric ulcers.<ref name="Sandin">Sandin, A, Skidell, J, Haggstrom, J, Nilsson, G (2000) ''Postmortem'' findings of gastric ulcers in Swedish horses older than age one year: a retrospective study of 3715 horses (1924–1996). ''Equine Vet J'', 32(1):36-42.</ref> This may be the reason that '''colic''' and other gastrointestinal disorders have been associated with EGUS.<ref>Furr, M.O, Murray, M.J (1989) Treatment of gastric ulcers in horses with histamine type 2 receptor antagonists. ''Equine Vet J Suppl'', 7:77-79.</ref> Alternatively, EGUS may be part of a more general gastrointestinal disease complex.<ref name="Vatistas 2">Vatistas, N.J, Sifferman, R.L, Holste, J, Cox, J.L, Pinalto, G, Schultz, K.T (1999) Induction and maintenance of gastric ulceration in horses in simulated race training. ''Equine Vet J Suppl'', 29:40-44</ref> ~~Gastrointestinal disorders: especially those resulting in delayed gastric emptying.~~<ref>Mertz, H.R, Walsh, J.H, (1991) Peptic ulcer pathophysiology. ''Med Clin North Am'', 75:799-814. In: Sanchez, L.C (2010) ''Diseases Of The Stomach'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), Saunders, Chapter 15.</ref>

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*'''Other ailments:''' conditions that produce abdominal pain and/or inappetance are likely to reduce food intake and predipose to gastric ulcers.<ref name="Sandin">Sandin, A, Skidell, J, Haggstrom, J, Nilsson, G (2000) ''Postmortem'' findings of gastric ulcers in Swedish horses older than age one year: a retrospective study of 3715 horses (1924–1996). ''Equine Vet J'', 32(1):36-42.</ref> This may be the reason that '''colic''' and other gastrointestinal disorders (especially those resulting in delayed gastric emptying) have been associated with EGUS.<ref>Furr, M.O, Murray, M.J (1989) Treatment of gastric ulcers in horses with histamine type 2 receptor antagonists. ''Equine Vet J Suppl'', 7:77-79.</ref> Alternatively, EGUS may be part of a more general gastrointestinal disease complex.<ref name="Vatistas 2">Vatistas, N.J, Sifferman, R.L, Holste, J, Cox, J.L, Pinalto, G, Schultz, K.T (1999) Induction and maintenance of gastric ulceration in horses in simulated race training. ''Equine Vet J Suppl'', 29:40-44</ref><ref>Mertz, H.R, Walsh, J.H, (1991) Peptic ulcer pathophysiology. ''Med Clin North Am'', 75:799-814. In: Sanchez, L.C (2010) ''Diseases Of The Stomach'' in Reed, S.M, Bayly, W.M. and Sellon, D.C (2010) '''Equine Internal Medicine''' (Third Edition), Saunders, Chapter 15.</ref>

*'''NSAIDs:''' As in [[Gastric Ulceration - all species|other species]], nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to cause gastric ulcers in horses. Typicaly this is associated with high doses or frequent administration of phenylbutazone or flunixin meglumine. However, although there is evidence to the contrary,<ref>Andrews, F.M, Reinemeyer, C.R, Longhofer, S.L (2009) Effects of top-dress formulations of suxibuzone and phenylbutazone on development of gastric ulcers in horses. ''Vet Ther'', 10(3):113-20.</ref>therapeutic doses of NSAIDs may be sufficient to induce EGUS. Other studies have suggested that suxibuzone causes significantly less ulcerogenic effects than phenylbutazone when administered orally<ref>Monreal, L, Sabatè, D, Segura, D, Mayós, I, Homedes, J (2004) Lower gastric ulcerogenic effect of suxibuzone compared to phenylbutazone when administered orally to horses. ''Res Vet Sci'', 76:145-149. In: Nadeau, J.A, Andrews, F.M (2009) ''Science: Overviews'' Equine gastric ulcer syndrome: The continuing conundrum. ''Equine Vet J'', 41(7):611-615.</ref>and that combination treatment with phenylbutazone and flunixin meglumine may be more risky than phenylbutazone alone.<ref>Reed, S.K, Messer, N.T, Tessman, R.K, Keegan, K.G (2006) Effects of phenylbutazone alone or in combination with flunixin meglumine on blood protein concentrations in horses. ''Am J Vet Res'', 67:398-402. In: Nadeau, J.A, Andrews, F.M (2009) ''Science: Overviews'' Equine gastric ulcer syndrome: The continuing conundrum. ''Equine Vet J'', 41(7):611-615.</ref> The ulcers produced by NSAIDs are unusual in that they have a predilection for the glandular mucosa<ref>MacAllister, C.G, Morgan, S.J, Borne, A.T, Pollet, R.A, (1993) Comparison of adverse effects of phenylbutazone, flunixin meglumine, and ketoprofen in horses. ''J Am Vet Med Ass'', 202:71-77. In: Jonsson, H, Egenvall, A (2006) Prevalence of gastric ulceration in Swedish Standardbreds in race training. ''Equine Vet J'', 38(3):209-213.</ref><ref>Furr, M.O, Murray, M.J (1989) Treatment of gastric ulcers in horses with histamine type 2 receptor antagonists. ''Equine Vet J Suppl'', 7:77-79. In: Vatistas, N.J, Sifferman, R.L, Holste, J, Cox, J.L, Pinalto, G, Schultz, K.T (1999) Induction and maintenance of gastric ulceration in horses in simulated race training. ''Equine Vet J Suppl'', 29:40-44</ref><ref>Kumaran, D, Bhuvanakumar, C.K (1994) Gastro duodenal ulceration in foals - a discussion. ''Cenfaur Mylapore'', 10:83-86. In: Vatistas, N.J, Sifferman, R.L, Holste, J, Cox, J.L, Pinalto, G, Schultz, K.T (1999) Induction and maintenance of gastric ulceration in horses in simulated race training. ''Equine Vet J Suppl'', 29:40-44</ref>, they may look different endoscopically from ulcers that occur naturally,<ref name="Jonsson">Jonsson, H, Egenvall, A (2006) Prevalence of gastric ulceration in Swedish Standardbreds in race training. ''Equine Vet J'', 38(3):209-213.</ref> and they appear to heal spontaneously.<ref>Jones, W.E (1983) Gastrointestinal ulcers [foal]. ''Equine Vet Data'', 4:305-308. In: Vatistas, N.J, Sifferman, R.L, Holste, J, Cox, J.L, Pinalto, G, Schultz, K.T (1999) Induction and maintenance of gastric ulceration in horses in simulated race training. ''Equine Vet J Suppl'', 29:40-44</ref><ref>MacAllister, C.G, Sangiah, S (1993) Effect of ranitidine (in healing of experimentally induced gastric ulcers in ponies. ''Am J Vet Res'', 54:1103-1107. In: Vatistas, N.J, Sifferman, R.L, Holste, J, Cox, J.L, Pinalto, G, Schultz, K.T (1999) Induction and maintenance of gastric ulceration in horses in simulated race training. ''Equine Vet J Suppl'', 29:40-44</ref> Despite the well-established link bewteen NSAIDs and ulcers, NSAIDs are rarely responsible for the lesions in horses in race training.<ref>Vatistas N.J, Snyder, J.R, Carlson, G.P, Johnson, B, Arther, R.M, Thurmiind, M, Lloyd, K.C.K (1994) Epidemiology study of gastric ulcerarion in the Thoroughbred race horse: 202 horses. ''Proc Am Ass Equine Pract'', 39:125-126. In: Vatistas, N.J, Sifferman, R.L, Holste, J, Cox, J.L, Pinalto, G, Schultz, K.T (1999) Induction and maintenance of gastric ulceration in horses in simulated race training. ''Equine Vet J Suppl'', 29:40-44</ref><ref>Murray, M.J, Schusser, G.F, Pipers, F.S, Gro:ss, S.J (1996) Factors associated with gastric lesions in Thoroughbred racehorses. ''Equine Vet J'', 28:368-374. In: Vatistas, N.J, Sifferman, R.L, Holste, J, Cox, J.L, Pinalto, G, Schultz, K.T (1999) Induction and maintenance of gastric ulceration in horses in simulated race training. ''Equine Vet J Suppl'', 29:40-44</ref><ref name="Vatistas thesis">Vatistas, N.J (1998) Gastric Ulceration in the Racing Thoroughbred. ''PhD Thesis''. In: Vatistas, N.J, Sifferman, R.L, Holste, J, Cox, J.L, Pinalto, G, Schultz, K.T (1999) Induction and maintenance of gastric ulceration in horses in simulated race training. ''Equine Vet J Suppl'', 29:40-44</ref>

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