Difference between revisions of "Effect of Diet on Behaviour"
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==Overview== | ==Overview== | ||
Several aspects of feeding can have an effect on behaviour: | Several aspects of feeding can have an effect on behaviour: | ||
| − | * Dietary composition: Nutrient composition, palatability, method of preservation (raw, dried, moist) | + | * Dietary composition: Nutrient composition, palatability, method of preservation (raw, dried, moist). |
| − | * Timing of access: Meal-feeding, on demand feeding, ad-lib feeding | + | * Timing of access: Meal-feeding, on demand feeding, ad-lib feeding. |
* Type of access: Bowl, simulated foraging (activity feeding) | * Type of access: Bowl, simulated foraging (activity feeding) | ||
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It is particularly important to ensure appropriate timing and type of access that satisfies species-specific time and energy allocation; cats and dogs would normally spent large parts of the day on foraging behaviour. A lack of opportunity to do this can lead to welfare and behaviour problems. | It is particularly important to ensure appropriate timing and type of access that satisfies species-specific time and energy allocation; cats and dogs would normally spent large parts of the day on foraging behaviour. A lack of opportunity to do this can lead to welfare and behaviour problems. | ||
| − | * Feral and wild cats allocate 6-8 hours every day on foraging (searching for prey and hunting). They eat 10-20 small meals each day, and return to | + | * Feral and wild cats allocate 6-8 hours every day on foraging (searching for prey and hunting). They eat 10-20 small meals each day, and return to hunting dirtily after consuming a meal. Frequency of hunting is not affected by satiation; cats will hunt whether hungry or not, but latency to kill-bite delivery is reduced when cats are hungry. |
* Feral dogs and wolves hunt more sporadically, as opportunities arise, but also spend several hours each day foraging (often searching for carrion and non-meat food). | * Feral dogs and wolves hunt more sporadically, as opportunities arise, but also spend several hours each day foraging (often searching for carrion and non-meat food). | ||
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====Protein, Tryptophan and Carbohydrate==== | ====Protein, Tryptophan and Carbohydrate==== | ||
| − | + | l-Tryptophan is large neutral amino acid (LNAA) which acts as a precursor for serotonin. l-Tryptophan is actively transported across the blood brain barrier by the L1 carrier<ref>Hawkins, R.A., O’Kane, R.L., Simpson, I.A., Vin ̃az, J.R. (2006) Structure of the Blood–Brain Barrier and Its Role in the Transport of Amino Acids. J. Nutr. 136: 218S–226S.</ref>. l-Tryptophan is therefore in competition for this carrier with other LNAAs (such as leucine, valine, methionine, histidine, isoleucine, tyrosine, phenylalanine, and threonine) leading to theories that l-tryptophan supplementation might increase serotoinin availability and therefore alter mood and behaviour. However, l-tryptophan is converted to kynurenine by the enzyme indoleamine 2,3,-dioygenase (IDO), which is activated by cortisol or pro-inflammatory cytokines<ref>Oxenkrug, G.F. (2010) Tryptophan–Kynurenine Metabolism as a Common Mediator of Genetic and Environmental Impacts in Major Depressive Disorder: The Serotonin Hypothesis Revisited 40 Years Later. Isr J Psychiatry Relat Sci. 47(1): 56–63.</ref>. Activation of IDO leads to depletion of l-tryptophan, and therefore of serotonin, which indicates a significant role in anxiety and depression<ref> Wichers, M.C., Maes, M. (2004) The role of indoleamine 2,3-dioxygenase (IDO) in the pathophysiology of interferon-α-induced depression. J Psychiatry Neurosci. 29(1):11-7.</ref> <ref>Elovainio, M., Hurme, M., Jokela, M., Pulkki-Råback, L., Kivimäki, M., Hintsanen, M., Hintsa, T., Lehtimäki, T., Viikari, J., Raitakari, O.T., Keltikangas-Järvinen, L. (2012) Indoleamine 2,3-dioxygenase activation and depressive symptoms: results from the Young Finns Study.Psychosom Med. 74(7):675-81.</ref>. Through IDO there is therefore an interaction between stress hormones (e.g. cortisol), inflammation and serotonin production. Supplementation of l-tryptophan in stressed individuals might therefore be expected to have variable effects. Supplementation with 5-hydroxytrptophan, which is converted directly to serotonin and bypasses IDO, might be expected to circumvent this problem. However, despite a large number of trials, evidence of the clinical effect of l-tryptophan supplementation in humans is weak, with a Cochrane Report concluding that evidence for effect above placebo was positive but of insufficient quality to be conclusive both for l-tryptophan and 5-hydroxytryptophan <ref>Shaw, K.A., Turner, J., Del Mar, C. (2008) Tryptophan and 5-Hydroxytryptophan for depressions.The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.</ref>. | |
Dysfunction of the serotonergic neurotransmitter system in dogs has been linked to a number of problems, including aggression<ref>Rosado, B., Garcia-Belenguer, S., Leon, M., et al. Blood concentrations of serotonin, cortisol, and dehydroepiandrosterone in aggressive dogs. Appl Anim Behav Sci 2010; 123:124-30</ref>. However, evidence for the efficacy of l-tryptophan supplemented diets is as equivocal and unreliable as in humans. | Dysfunction of the serotonergic neurotransmitter system in dogs has been linked to a number of problems, including aggression<ref>Rosado, B., Garcia-Belenguer, S., Leon, M., et al. Blood concentrations of serotonin, cortisol, and dehydroepiandrosterone in aggressive dogs. Appl Anim Behav Sci 2010; 123:124-30</ref>. However, evidence for the efficacy of l-tryptophan supplemented diets is as equivocal and unreliable as in humans. | ||
| − | In both dogs and cats fed a | + | In both dogs and cats fed a L-tryptophan supplement, lower levels of behaviours related to stress and fewer signs of anxiety were seen in one study, but this was not in a peer-reviewed journal<ref>Da Graca Pereira, G., Fragoso, S., L-tryptophan supplementation and its effect of multi-housed cats and working dogs. Proceedings of the 2010 European Veterinary Behaviour Meeting. Hamburg, 2010, 30-35</ref>. In another study, an axiolytic effect was fond, but the diet contained alpha-casozepine as well as l-tryptophan, so any effect cannot be ascribed to amino acid acid supplementation alone<ref name="Kato">Kato, M., Miyaji, K., Ohtani, N., et al. (2012) Effects of prescription diet on dealing with stressful situations and performance of anxiety-related behaviours in privately owned anxious dogs. Journal of Veterinary Behavior: Clinical Applications and Research. 7(1). 21–26.</ref>. A randomised double-blinded, placebo-controlled study showed no effect of an l-tryptophan enriched diet on behaviour or salivary cortisol in dogs, despite measurable increases in plasma levels of the amino acid<ref name="Kato">Kato, M., Miyaji, K., Ohtani, N., et al. (2012) Effects of prescription diet on dealing with stressful situations and performance of anxiety-related behaviours in privately owned anxious dogs. Journal of Veterinary Behavior: Clinical Applications and Research. 7(1). 21–26.</ref>Bosch, G., Beerda, B., Beynen, A.C., van der Borg, J.A.M., b, van der Poel, A.F.B., Hendriks, W.H., (2009) Dietary tryptophan supplementation in privately owned mildly anxious dogs. Applied Animal Behaviour Science. 121. 197–205</ref>. |
| − | The effect of dietary protein content is also uncertain. In one study feeding dogs a diet with a lower protein content decreased territorial aggression (territorial aggression that had a fearful underlying motivation)<ref>Dodman, N.H., Reisner, I., Shuster, L., et al. Effect of dietary protein content on behaviour of dogs. J Am Vet Med Assoc 1996; 208:376-9</ref>, although other types of aggression seemed to be uninfluenced. In another, protein content and relative level to l-tryptophan were found to affect different forms of aggression<ref>DeNapoli, J.S., Dodman, N.H., Shuster, L., Rand, W.M., Gross, K.L. (2000) Effect of dietary protein content and tryptophan supplementation on dominance aggression, territorial aggression, and hyperactivity in dogs. J Am Vet Med Assoc. 217(4):504-8.</ref>. | + | The effect of dietary protein content is also uncertain. In one study feeding dogs a diet with a lower protein content decreased territorial aggression (territorial aggression that had a fearful underlying motivation)<ref>Dodman, N.H., Reisner, I., Shuster, L., et al. Effect of dietary protein content on behaviour of dogs. J Am Vet Med Assoc 1996; 208:376-9</ref>, although other types of aggression seemed to be uninfluenced. In another, protein content and relative level to l-tryptophan were found to affect different forms of aggression<ref>DeNapoli, J.S., Dodman, N.H., Shuster, L., Rand, W.M., Gross, K.L. (2000) Effect of dietary protein content and tryptophan supplementation on dominance aggression, territorial aggression, and hyperactivity in dogs.J Am Vet Med Assoc. 217(4):504-8.</ref>. |
Increasing carbohydrate level in the diet has also been proposed as a means of altering anxiety in dogs and cats, but such diets also include a reduced protein content. | Increasing carbohydrate level in the diet has also been proposed as a means of altering anxiety in dogs and cats, but such diets also include a reduced protein content. | ||
====Pyridoxine==== | ====Pyridoxine==== | ||
| − | + | Pyridoxine or vitamin B<sub>6</sub> assists in the fabrication of serotonin,<ref name="Kato" /> which in turn is linked to a reduction in anxiety and aggression. | |
====Fatty Acids==== | ====Fatty Acids==== | ||
| − | For cats, cis-linoleic and arachidonic acid are essential | + | For cats, cis-linoleic and arachidonic acid are essential for life.However, other fatty acids, specifically long-chain omega-3; docosahexaenoic acid (DHA), are fundamental for certain aspects of development (both neuronal and retinal) and for neurotransmission. They also help to combat oxidative stress.<ref>Innis, S.M. Dietary (n-3) fatty acids and brain development. J Nutr 2007:137:855-9</ref>. Eicosapentaenoic acid (EPA) has an important anti-inflammatory effect. The conversion of alpha-linolenic acid to long-chain EPA and DHA is very inefficacious<ref name="Zicker"> Zicker, S.C, Jewell, D.E., Yamka, R.M., et al. Evaluation of cognitive learning, memory, psychomotor, immunologic, and retinal functions in healthy puppies fed foods fortified with docosahexanoeic acid-rich fish oil from 8-52 weeks. J Am Vet Med Assoc 2012;241:583-94</ref>. These can be added to the diet as a supplement and may be particularly important in gestation, lactation and post-weaning<ref>Bauer, J.E., Heinemann, K.M., Lees, G.E., et al. Retinal functions of young dogs are improved and maternal plasma phospholipids are altered with diets containing long-chain n-3 polyunsaturated fatty acids during gestation, lactation, and after weaning. J Nutr 2006;1191S-994S</ref>. Further to the already mentioned effects DHA supplementation has been linked to an improved memory, cognitive, psychomotor and immunologic function and better problem-solving skills in puppies<ref>Heinemann, K.M., Bauer, J.E., Docosaheaenoic acid and neurologic development in animals. J Am Vet Med Assoc 2006;228:700-6</ref><ref name="Zicker"/>, this is also likely to be applicable to felines. |
| − | + | ==Behavioural Problems Related to Diet and Their Diagnosis== | |
| + | If it is thought that diet may be a contributing factor to behavioural problems the theory should be tested by trial and exclusion. The new diet, potentially with lower protein levels should be fed for a 1-2 weeks, taking note of any differences in behaviour and then returning the animal to the initial diet to see if behaviours which ceased or became reduced during the trial period return. Before implementing a trial diet a careful clinical examination should be performed and blood and urine samples should be taken to ensure these are normal. If a homemade diet is going to be used for the trial period, this should consist of the same amount of meat and carbohydrate, one part of each and the same quantity should be fed as of the diet it is replacing. No supplements or treats or other types of food should be fed during the trial. Alternatives to a homemade diet include using prescription diets which are already low in protein, for example a canned renal diet. It is also important to consider the difference between diets which contain additives and preservatives - dry foods, and those which don't - canned foods or homemade diets and whether this is also an influencing factor on behaviour. | ||
| − | + | ==Control of Diet Associated Behavioural Problems== | |
| − | + | It should be noted that a homemade diet is not a balanced diet for long-term use, and although is not likely to cause a problem for the trial period of 1-2 weeks it should not be fed long term. A nutritionist should be consulted if it is decided to continue with a home-produced diet to ensure that it is nutritionally balanced and contains all the necessary components. Prescription renal diets are a nutritionally balanced alternative. With other foods it is important to looks for those which contain a good-quality protein in conservative amounts with a carbohydrate source which is easily digestible. Canned foods generally have fewer, or no preservatives and dry foods generally have most preservatives. If behaviour deteriorates when a commercial formulation is reintroduced other problems apart from solely the protein content should be considered. | |
| − | + | ==Prevention of Diet Associated Behavioural Problems== | |
| − | + | Complete prevention of diet related behavioural problems is not normally possible as they are difficult to predict. On average, most pets consume a diet which contains far higher levels of protein than are necessary to satisfy amino-acid needs. Some anecdotal evidence points to some breeds being more sensitive to certain dietary components. For example the Cavalier King Charles spaniel may be more sensitive to preservatives and Golden Retrievers to exorphines, as well as others which may react to different meat proteins affecting serotonin<ref>Ballarni, G. Animal psychodietetics. J Small Anim Pract 1990;31:523-32</ref>. However, further research is necessary to investigate these suggestions. | |
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==References== | ==References== | ||
<references/> | <references/> | ||
| + | *Landsberg, G.M., Hunthausen, W.L., Ackermann, L.J. 2013. Behaviour Problems of the Dog and Cat. Third Edition. Saunders Elsevier. | ||
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[[Category:Feline Behaviour Management]] | [[Category:Feline Behaviour Management]] | ||
| + | [[Category:JBowen reviewing]] | ||
Revision as of 11:26, 2 July 2014
Overview
Several aspects of feeding can have an effect on behaviour:
- Dietary composition: Nutrient composition, palatability, method of preservation (raw, dried, moist).
- Timing of access: Meal-feeding, on demand feeding, ad-lib feeding.
- Type of access: Bowl, simulated foraging (activity feeding)
All of these should be taken into account when designing a feeding regime for domestic cats and dogs.
Feeding Pattern
It is particularly important to ensure appropriate timing and type of access that satisfies species-specific time and energy allocation; cats and dogs would normally spent large parts of the day on foraging behaviour. A lack of opportunity to do this can lead to welfare and behaviour problems.
- Feral and wild cats allocate 6-8 hours every day on foraging (searching for prey and hunting). They eat 10-20 small meals each day, and return to hunting dirtily after consuming a meal. Frequency of hunting is not affected by satiation; cats will hunt whether hungry or not, but latency to kill-bite delivery is reduced when cats are hungry.
- Feral dogs and wolves hunt more sporadically, as opportunities arise, but also spend several hours each day foraging (often searching for carrion and non-meat food).
For cats, the most ethologically appropriate presentation of food is ad-lib using simulated foraging (activity feeders). A cat given 2 meals per day is effectively having its feeding frequency reduced to the equivalent of a person being fed every 2nd or 3rd day.
For dogs, some opportunity for simulated foraging should also be provided, in the form of activity feeders.
Dietary Components Which Affect Behaviour
Certain dietary components have an effect on an animals behaviour, leading to the possibility that behaviour may be manipulated using a modified diet.
Protein, Tryptophan and Carbohydrate
l-Tryptophan is large neutral amino acid (LNAA) which acts as a precursor for serotonin. l-Tryptophan is actively transported across the blood brain barrier by the L1 carrier[1]. l-Tryptophan is therefore in competition for this carrier with other LNAAs (such as leucine, valine, methionine, histidine, isoleucine, tyrosine, phenylalanine, and threonine) leading to theories that l-tryptophan supplementation might increase serotoinin availability and therefore alter mood and behaviour. However, l-tryptophan is converted to kynurenine by the enzyme indoleamine 2,3,-dioygenase (IDO), which is activated by cortisol or pro-inflammatory cytokines[2]. Activation of IDO leads to depletion of l-tryptophan, and therefore of serotonin, which indicates a significant role in anxiety and depression[3] [4]. Through IDO there is therefore an interaction between stress hormones (e.g. cortisol), inflammation and serotonin production. Supplementation of l-tryptophan in stressed individuals might therefore be expected to have variable effects. Supplementation with 5-hydroxytrptophan, which is converted directly to serotonin and bypasses IDO, might be expected to circumvent this problem. However, despite a large number of trials, evidence of the clinical effect of l-tryptophan supplementation in humans is weak, with a Cochrane Report concluding that evidence for effect above placebo was positive but of insufficient quality to be conclusive both for l-tryptophan and 5-hydroxytryptophan [5].
Dysfunction of the serotonergic neurotransmitter system in dogs has been linked to a number of problems, including aggression[6]. However, evidence for the efficacy of l-tryptophan supplemented diets is as equivocal and unreliable as in humans.
In both dogs and cats fed a L-tryptophan supplement, lower levels of behaviours related to stress and fewer signs of anxiety were seen in one study, but this was not in a peer-reviewed journal[7]. In another study, an axiolytic effect was fond, but the diet contained alpha-casozepine as well as l-tryptophan, so any effect cannot be ascribed to amino acid acid supplementation alone[8]. A randomised double-blinded, placebo-controlled study showed no effect of an l-tryptophan enriched diet on behaviour or salivary cortisol in dogs, despite measurable increases in plasma levels of the amino acid[8]Bosch, G., Beerda, B., Beynen, A.C., van der Borg, J.A.M., b, van der Poel, A.F.B., Hendriks, W.H., (2009) Dietary tryptophan supplementation in privately owned mildly anxious dogs. Applied Animal Behaviour Science. 121. 197–205</ref>.
The effect of dietary protein content is also uncertain. In one study feeding dogs a diet with a lower protein content decreased territorial aggression (territorial aggression that had a fearful underlying motivation)[9], although other types of aggression seemed to be uninfluenced. In another, protein content and relative level to l-tryptophan were found to affect different forms of aggression[10].
Increasing carbohydrate level in the diet has also been proposed as a means of altering anxiety in dogs and cats, but such diets also include a reduced protein content.
Pyridoxine
Pyridoxine or vitamin B6 assists in the fabrication of serotonin,[8] which in turn is linked to a reduction in anxiety and aggression.
Fatty Acids
For cats, cis-linoleic and arachidonic acid are essential for life.However, other fatty acids, specifically long-chain omega-3; docosahexaenoic acid (DHA), are fundamental for certain aspects of development (both neuronal and retinal) and for neurotransmission. They also help to combat oxidative stress.[11]. Eicosapentaenoic acid (EPA) has an important anti-inflammatory effect. The conversion of alpha-linolenic acid to long-chain EPA and DHA is very inefficacious[12]. These can be added to the diet as a supplement and may be particularly important in gestation, lactation and post-weaning[13]. Further to the already mentioned effects DHA supplementation has been linked to an improved memory, cognitive, psychomotor and immunologic function and better problem-solving skills in puppies[14][12], this is also likely to be applicable to felines.
Behavioural Problems Related to Diet and Their Diagnosis
If it is thought that diet may be a contributing factor to behavioural problems the theory should be tested by trial and exclusion. The new diet, potentially with lower protein levels should be fed for a 1-2 weeks, taking note of any differences in behaviour and then returning the animal to the initial diet to see if behaviours which ceased or became reduced during the trial period return. Before implementing a trial diet a careful clinical examination should be performed and blood and urine samples should be taken to ensure these are normal. If a homemade diet is going to be used for the trial period, this should consist of the same amount of meat and carbohydrate, one part of each and the same quantity should be fed as of the diet it is replacing. No supplements or treats or other types of food should be fed during the trial. Alternatives to a homemade diet include using prescription diets which are already low in protein, for example a canned renal diet. It is also important to consider the difference between diets which contain additives and preservatives - dry foods, and those which don't - canned foods or homemade diets and whether this is also an influencing factor on behaviour.
Control of Diet Associated Behavioural Problems
It should be noted that a homemade diet is not a balanced diet for long-term use, and although is not likely to cause a problem for the trial period of 1-2 weeks it should not be fed long term. A nutritionist should be consulted if it is decided to continue with a home-produced diet to ensure that it is nutritionally balanced and contains all the necessary components. Prescription renal diets are a nutritionally balanced alternative. With other foods it is important to looks for those which contain a good-quality protein in conservative amounts with a carbohydrate source which is easily digestible. Canned foods generally have fewer, or no preservatives and dry foods generally have most preservatives. If behaviour deteriorates when a commercial formulation is reintroduced other problems apart from solely the protein content should be considered.
Prevention of Diet Associated Behavioural Problems
Complete prevention of diet related behavioural problems is not normally possible as they are difficult to predict. On average, most pets consume a diet which contains far higher levels of protein than are necessary to satisfy amino-acid needs. Some anecdotal evidence points to some breeds being more sensitive to certain dietary components. For example the Cavalier King Charles spaniel may be more sensitive to preservatives and Golden Retrievers to exorphines, as well as others which may react to different meat proteins affecting serotonin[15]. However, further research is necessary to investigate these suggestions.
References
- ↑ Hawkins, R.A., O’Kane, R.L., Simpson, I.A., Vin ̃az, J.R. (2006) Structure of the Blood–Brain Barrier and Its Role in the Transport of Amino Acids. J. Nutr. 136: 218S–226S.
- ↑ Oxenkrug, G.F. (2010) Tryptophan–Kynurenine Metabolism as a Common Mediator of Genetic and Environmental Impacts in Major Depressive Disorder: The Serotonin Hypothesis Revisited 40 Years Later. Isr J Psychiatry Relat Sci. 47(1): 56–63.
- ↑ Wichers, M.C., Maes, M. (2004) The role of indoleamine 2,3-dioxygenase (IDO) in the pathophysiology of interferon-α-induced depression. J Psychiatry Neurosci. 29(1):11-7.
- ↑ Elovainio, M., Hurme, M., Jokela, M., Pulkki-Råback, L., Kivimäki, M., Hintsanen, M., Hintsa, T., Lehtimäki, T., Viikari, J., Raitakari, O.T., Keltikangas-Järvinen, L. (2012) Indoleamine 2,3-dioxygenase activation and depressive symptoms: results from the Young Finns Study.Psychosom Med. 74(7):675-81.
- ↑ Shaw, K.A., Turner, J., Del Mar, C. (2008) Tryptophan and 5-Hydroxytryptophan for depressions.The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
- ↑ Rosado, B., Garcia-Belenguer, S., Leon, M., et al. Blood concentrations of serotonin, cortisol, and dehydroepiandrosterone in aggressive dogs. Appl Anim Behav Sci 2010; 123:124-30
- ↑ Da Graca Pereira, G., Fragoso, S., L-tryptophan supplementation and its effect of multi-housed cats and working dogs. Proceedings of the 2010 European Veterinary Behaviour Meeting. Hamburg, 2010, 30-35
- ↑ 8.0 8.1 8.2 Kato, M., Miyaji, K., Ohtani, N., et al. (2012) Effects of prescription diet on dealing with stressful situations and performance of anxiety-related behaviours in privately owned anxious dogs. Journal of Veterinary Behavior: Clinical Applications and Research. 7(1). 21–26.
- ↑ Dodman, N.H., Reisner, I., Shuster, L., et al. Effect of dietary protein content on behaviour of dogs. J Am Vet Med Assoc 1996; 208:376-9
- ↑ DeNapoli, J.S., Dodman, N.H., Shuster, L., Rand, W.M., Gross, K.L. (2000) Effect of dietary protein content and tryptophan supplementation on dominance aggression, territorial aggression, and hyperactivity in dogs.J Am Vet Med Assoc. 217(4):504-8.
- ↑ Innis, S.M. Dietary (n-3) fatty acids and brain development. J Nutr 2007:137:855-9
- ↑ 12.0 12.1 Zicker, S.C, Jewell, D.E., Yamka, R.M., et al. Evaluation of cognitive learning, memory, psychomotor, immunologic, and retinal functions in healthy puppies fed foods fortified with docosahexanoeic acid-rich fish oil from 8-52 weeks. J Am Vet Med Assoc 2012;241:583-94
- ↑ Bauer, J.E., Heinemann, K.M., Lees, G.E., et al. Retinal functions of young dogs are improved and maternal plasma phospholipids are altered with diets containing long-chain n-3 polyunsaturated fatty acids during gestation, lactation, and after weaning. J Nutr 2006;1191S-994S
- ↑ Heinemann, K.M., Bauer, J.E., Docosaheaenoic acid and neurologic development in animals. J Am Vet Med Assoc 2006;228:700-6
- ↑ Ballarni, G. Animal psychodietetics. J Small Anim Pract 1990;31:523-32
- Landsberg, G.M., Hunthausen, W.L., Ackermann, L.J. 2013. Behaviour Problems of the Dog and Cat. Third Edition. Saunders Elsevier.