Cachexia: Pathophysiology and clinical relevance

American Journal of Clinical Nutrition

Volumn 83, Issue 4, 2006, Pages 735-743

  Morley, John E ^a,b   Thomas, David R ^a   Wilson, Margaret Mary G ^a  

^a SAINT LOUIS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

Cachexia; Pathogenesis; Sarcopenia; Weight loss

Indexed keywords

APPETITE STIMULANT; CYTOKINE; CYTOKINE ANTIBODY; CYTOKINE RECEPTOR; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; ETANERCEPT; GESTAGEN; GLUCOCORTICOID; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; ICOSAPENTAENOIC ACID; MEGESTROL ACETATE; MYOSTATIN; NONSTEROID ANTIINFLAMMATORY AGENT; PENTOXIFYLLINE; SOMATOMEDIN C; TESTOSTERONE; THALIDOMIDE; TRANSFORMING GROWTH FACTOR BETA;

AGING; ANOREXIA; CACHEXIA; CANCER; CHRONIC KIDNEY FAILURE; CHRONIC OBSTRUCTIVE LUNG DISEASE; DEHYDRATION; DISEASE ASSOCIATION; HEART DISEASE; HUMAN; MORTALITY; MUSCLE ATROPHY; NUTRITIONAL SUPPORT; PATHOPHYSIOLOGY; PREVALENCE; PROTEIN BLOOD LEVEL; REVIEW; RHEUMATOID ARTHRITIS; UNITED STATES; WASTING SYNDROME; WEIGHT REDUCTION; BLOOD; CHRONIC DISEASE; NEOPLASM; PATHOLOGY; PHYSIOLOGY;

AGING; ANOREXIA; ARTHRITIS, RHEUMATOID; CACHEXIA; CHRONIC DISEASE; CYTOKINES; GLUCOCORTICOIDS; HIV WASTING SYNDROME; HUMANS; INSULIN-LIKE GROWTH FACTOR I; KIDNEY FAILURE, CHRONIC; NEOPLASMS; PULMONARY DISEASE, CHRONIC OBSTRUCTIVE; TESTOSTERONE; TRANSFORMING GROWTH FACTOR BETA; WEIGHT LOSS;

EID: 33646674302     PISSN: 00029165     EISSN: None     Source Type: Journal    
DOI: 10.1093/ajcn/83.4.735     Document Type: Review

References (143)

1. Sharma R, Anker S. First cachexia symposium. Berlin, Germany: 1st-2nd December, 2000. Eur J Heart Fail 2000;3:751-4.
2. Thomas DR. Distinguishing starvation from cachexia. Clin Geriatr Med 2002;18:883-91.
3. Roubenoff R, Heymsfield SB, Kehayias JJ, Cannon JG, Rosenberg IH. Standardization of nomenclature of body composition in weight loss. Am J Clin Nutr 1997;66:192-6.
4. Roubenoff R, Parise H, Payette HA, et al. Cytokines, insulin-like growth factor 1, sarcopenia, and mortality in very old community-dwelling men and women: the Framingham Heart Study. Am J Med 2003;115:429-35.
5. Ferrucci L, Penninx BWJH, Volpato S, et al. Change in muscle strength explains accelerated decline in physical function in older women with high interleukin-6 serum levels. J Am Geriatr Soc 2002;50:1947-54.
6. Morley JE. Anorexia, sarcopenia, and aging. Nutrition 2001;17:660-3.
7. Morley JE, Baumgartner R. Cytokine related aging process. J Gerontol Med Sci 2004;59A:924-9.
8. Wilkinson TJ, Warren MR. What is the prognosis of mild normocytic anemia in older people? Int Med J 2003;33:14-7.
9. Kotler DP. Cachexia. Ann Intern Med 2000;1333:622-34.
10. Guttridge DC, Mayo MW, Madrid LV, Wang CY, Baldwin AS Jr. NF-κB-induced loss of MyoD messenger RNA; possible role in muscle decay and cachexia. Science 2000;289:2363-6.
11. Wheeler MT, Snyder EC, Patterson MN, Swoap SJ. An E-box within the MHC IIB gene is bound by MyoD and is required for gene expression in fast muscle. Am J Physiol 1999;276:C1069-78.
12. Acharyya S, Ladner KJ, Nelsen LL, et al. Cancer cachexia is regulated by selective targeting of skeletal muscle gene products. Cancer cachexia is regulated by selective targeting of skeletal muscle gene products. J Clin Invest 2004;114:370-8.
13. Mitch WE, Goldberg AL. Mechanisms of muscle wasting. The role of the ubiquitin-proteasome pathway. N Engl J Med 1996;335:1897-905.
14. Shintani F, Nakaki T, Kanba S, Kato R, Asai M. Role of interleukin-1 in stress responses. A putative neurotransmitter. Mol Neurobiol 1995;10:47-71.
15. Pende A, Musso NR, Vergassola C, et al. Neuroendocrine effects of interferon alpha 2-a in healthy human subjects. J Biol Regul Homeost Agents 1990;4:67-72.
16. Ryden M, Arvidsson E, Blomqvist L, Perbeck L, Dicker A, Arner P. Targets for TNF-alpha-induced lipolysis in human adipocytes. Biochem Biophys Res Commun 2004;318:168-75.
17. Liao W, Floren CH. Upregulation of low density lipoprotein receptor activity by tumor necrosis factor, a process independent of tumor necrosis factor-induced lipid synthesis and secretion. Lipids 1994;29:679-84.
18. Feingold KR, Marshall M, Gulli R, Moser AH, Grunfeld C. Effect of endotoxin and cytokines on lipoprotein lipase activity in mice. Arterioscler Thromb 1994;14:1866-72.
19. Grunfeld C, Feingold KR. Regulation of lipid metabolism by cytokines during host defense. Nutrition 1996;12(suppl):S24-6.
20. Morley JE, Kaiser FE, Perry HM, et al. Longitudinal changes in testosterone, luteinizing hormone, and follicle-stimulating hormone in healthy older men. Metab Clin Exp 1997;46:410-3.
21. Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR. Baltimore Longitudinal Study of Aging. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. J Clin Endocrinol Metab 2001;86:724-31.
22. Morley JE, Melmed S. Gonadal dysfunction in systemic disorders. Metabolism 1979;28:1051-73.
23. Bhasin S, Taylor WE, Singh R, et al. The mechanisms of androgen effects on body composition: mesenchymal pluripotent cell as the target of androgen action. J Gerontol Med Sci 2003;58A:M1103-10.
24. D'Agostino P, Milano S, Barbera C, et al. Sex hormone modulate inflammatory mediators produced by macrophages. Ann NY Acad Sci 1999;876:426-9.
25. Li ZG, Danis VA, Brooks PM. Effect of gonadal steroids on the production of IL-1 and IL-6 by blood mononuclear cells in vitro. Clin Exp Rheumatol 1993;11:157-62.
26. Malkin CJ, Pugh PJ, Jones RD, Kapoor D, Channer KS, Jones TH. The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. J Clin Endocrinol Metab 2004;89:3313-8.
27. Baumgartner RN, Waters DL, Morley JE, Patrick P, Montoya GD, Garry PJ. Age-related changes in sex hormones affect the sex difference in serum leptin independently of changes in body fat. Metab Clin Exp 1999;48:378-84.
28. Sih R, Morley JE, Kaiser Fe, Perry HM, Patrick P, Ross C. Testosterone replacement in older hypogonadal men - a 12-month randomized controlled trial. J Clin Endocrinol Metab 1997;82:1661-7.
29. Baumgartner RN, Waters DL, Gallagher D, Morley JE, Garry PJ. Predictors of skeletal muscle mass in elderly men and women. Mech Ageing Dev 1999;107:123-36.
30. Iannuzzi-Sucich M, Prestwood KM, Kenny AM. Prevalence of sarcopenia and predictors of skeletal muscle mass in healthy, older men and women. J Gerontol Med Sci 2002;57A:M772-7.
31. Giovannucci E, Pollak M, Liu Y, et al. Nutritional predictors of insulin-like growth factor I and their relationships to cancer in men. Cancer Epidemiol Biomarkers Prev 2003;12:84-9.
32. Allen NE, Appleby PN, Davey GK, Kaaks R, Rinaldi S, Key TJ. The associations of diet with serum insulin-like growth factor I and its main binding proteins in 292 women meat-eaters, vegetarians, and vegans. Cancer Epidemiol Biomarkers Prev 2002;11:1441-8.
33. Fang CH, Li BG, Wang JJ, Fischer JE, Hasselgren PO. Insulin-like growth factor 1 stimulates protein synthesis and inhibits protein breakdown in muscle from burned rats. JPEN J Parenter Enteral Nutr 1997;21:245-51.
34. Tirapegui J. Effect of insulin-like growth factor-1 (IGF-1) on muscle and bone growth in experimental models. Int J Food Sci Nutr 1999;50:231-6.
35. Barton ER, Morris L, Musaro A, Rosenthal N, Sweeney HL. Muscle-specific expression of insulin-like growth factor I counters muscle decline in MDX mice. J Cell Biol 2002;157:137-47.
36. Musaro A, McCullagh K, Paul A, et al. Localized IgF-1 transgene expression sustains hypertrophy and regeneration in senescent skeletal muscle. Nat Genet 2001;27:195-200.
37. Caregaro L, Favaro A, Santonastaso P, et al. Insulin-like growth factor 1 (IGF-1), a nutritional marker in patients with eating disorders. Clin Nutr 2001;20:251-7.
38. Ponzer S, Tidermark J, Brismar K, Soderqvist A, Cederholm T. Nutritional status, insulin-like growth factor-1 and quality of life in elderly women with hip fractures. Clin Nutr 1999;18:241-6.
39. Caregaro L, Alberino F, Amodio P, et al. Nutritional and prognostic significance of insulin-like growth factor 1 in patients with liver cirrhosis. Nutrition 1997;13:185-90.
40. Roth SM, Walsh S. Myostatin: a therapeutic target for skeletal muscle wasting. Curr Opin Clin Nutr Metab Care 2004;7:259-63.
41. McPherron AC, Lee S-J. Double muscling in cattle due to mutations in the myostatin gene. Proc Natl Acad Sci U S A 1997;94:12457-61
42. Grobet L, Martin LJR, Poncelet D, et al. A deletion in the bovine myostatin gene causes the double-muscled phenotype in cattle. Nat Genet 1997;17:71-4.
43. Lin J, Arnold HB, Della-Fera MA, et al. Myostatin knockout in mice increases myogenesis and decreases adipogenesis. Biochem Biophys Res Commun 2002;291:701-6.
44. Schuelke M, Wagner KR, Stolz LE, et al. Brief report - myostatin mutation associated with gross muscle hypertrophy in a child. N Engl J Med 2004;250:2682-8.
45. Zimmers TA, Davies MV, Koniaris LG, et al. Induction of cachexia in mice by systemically administered myostatin. Science 2002;296:1486-8.
46. Ewart HS, Somwar R, Klip A. Dexamethasone stimulates the expression of GLUT1 and GLUT4 proteins with different signaling pathways in L6 skeletal muscle cells. FEBS Lett 1998;425:179-83.
47. Dimitriadis G, Leighton B, Parry-Billings M, et al. Effects of glucocorticoid excess on the sensitivity of glucose transport and metabolism to insulin in rat skeletal muscle. Biochem J 1997;321:707-12.
48. Wing SS, Goldberg AL. Glucocorticoids activate the ATP-ubiquitin- dependent proteolytic system in skeletal muscle during fasting. Am J Physiol 1993;264:E668-76.
49. Anker SD, Negassa A, Coats AJ, et al. Prognostic importance of weight loss in chronic heart failure and the effect of treatment with angiotensin-converting-enzyme inhibitors: an observational study. Lancet 2003;361:1077-83.
50. The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 1991;325:293-302.
51. Anker SD, von Haehling S. Inflammatory mediators in chronic heart failure: an overview. Heart 2004;90:464-70.
52. Anker SD, Ponikowski PP, Clark AL, et al. Cytokines and neurohormones relating to body composition alterations in the wasting syndrome of chronic heart failure. Eur Heart J 1999;20:683-93.
53. Cicoira M, Bolger AP, Doehner W, et al. High tumour necrosis factor-alpha levels are associated with exercise intolerance and neurohormonal activation in chronic heart failure patients. Cytokine 2001;15:80-6.
54. Anker SD. Has the time arrived to use anticytokine therapy in chronic heart failure. Dialogues Cardiovasc Med 2000;5:162-70.
55. Liu L, Zhao SP. The changes of circulating tumor necrosis factor levels in patients with congestive heart failure influenced by therapy. Int J Cardiol 1999;69:77-82.
56. Gullestad L, Aukrust P, Ueland T, et al. Effect of high-versus low-dose angiotensin converting enzyme inhibition on cytokine levels in chronic heart failure. J Am Coll Cardiol 1999;34:2061-7.
57. Sigurdsson A, Swedberg K, Ullman B. Effects of ramipril on the neurohormonal response to exercise in patients with mild or moderate congestive heart failure. Eur Heart J 1994;15:247-54.
58. Mann DL, McMurray JJ, Packer M, et al. Targeted anticytokine therapy in patients with chronic heart failure: results of Randomized Etanercept Worldwide Evaluation (RENEWAL). Circulation 2004;109:1594-602.
59. Bozkurt B, Torre-Amione G, Warren MS, et al. Results of targeted anti-tumor necrosis factor therapy with etanercept in patients with advanced heart failure. Circulation 2001;103:1044-7.
60. Chung ES, Packer M, Lo KH, Fasanmade AA, Willerson JT, AntiTNF Therapy Against Congestive Heart Failure Investigators. Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor alpha, in patients with moderate-to-severe heart failure: results of the anti-TNF Therapy Against Congestive Heart Failure (ATTACHF) trial. Circulation 2003;107:3133-40.
61. Cano W. Malnutrition and chronic renal failure. Ann Med Interne (Paris) 2000;151:563-74.
62. Garg AX, Blake PG, Clark WF, Clase CM, Haynes RB, Moist LM. Association between renal insufficiency and malnutrition in older adults: results from the NHAMES III. Kidney Int 2001;60:1867-74.
63. Guarnieri G, Toigo G, Fiotti N, et al. Mechanisms of malnutrition in uremia. Kidney Int 1997;62(suppl):S41-4.
64. Kalantar-Zadeh K, Stenvinkel P, Bross R, et al. Kidney insufficiency and nutrient-based modulation of inflammation. Curr Opin Clin Nutr Metab Care 2005;8:388-96.
65. Lundholm K, Daneryd P, Bosaeus I, Korner U, Lindholm E. Palliative nutritional intervention in addition to cyclooxygenase and erythropoietin treatment for patients with malignant disease: effects on survival, metabolism, and function. Cancer 2004;100:1967-77.
66. Bergstrom J. Regulation of appetite in chronic renal failure. Miner Electrolyte Metab 1999;25:291-7.
67. Van Vlem B, Schoonjans R, Vanholder R, et al. Delayed gastric emptying in dyspeptic chronic hemodialysis patients. Am J Kidney Dis 2000;36:962-8.
68. De Schoenmakere G, Vanholder R, Rottey S, Duym P, Lameire N. Relationship between gastric emptying and clinical and biochemical factors in chronic hemodialysis patients. Nephrol Dial Transplant 2001;16:1850-5.
69. Mitch WE, Du J, Bailey JL, Price SR. Mechanisms causing muscle proteolysis in uremia: the influence of insulin and cytokines. Miner Electrolyte Metab 1999;25:216-9.
70. Reid MB. COPD as a muscle disease. Am J Respir Crit Care Med 2001;164:1101-2.
71. Schols AM, Slangen J, Volovics L, et al. Weight loss is a reversible factor in the prognosis of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998;157:1791-7.
72. Mostert R, Goris A, Weling-Scheepers C, et al. Tissue depletion and health related quality of life in patients with chronic obstructive pulmonary disease. Respir Med 2000;94:859-67.
73. Farber MO, Mannix ET. Tissue wasting in patients with chronic obstructive pulmonary disease, the acquired immune deficiency syndrome, and congestive heart failure. Neurol Clin 2000;18:245-62.
74. Hasegawa Y, Sawada M, Ozaki N, et al. Increased soluble tumor necrosis factor receptor levels in the serum of elderly people. Gerontology 2000;46:185-8.
75. Agusti A, Morla M, Sauleda J, Saus C, Busquets X. NF-kappa β activation and iNOS upregulation in skeletal muscle of patients with COPD and low body weight. Thorax 2004;59:483-7.
76. Schols A. Nutritional modulation as part of the integrated management of chronic obstructive pulmonary disease. Proc Nutr Soc 2003;62:783-91.
77. Weisberg J, Wanger J, Olson J, et al. Megestrol acetate stimulates weight gain and ventilation in underweight COPD patients. Chest 2002;121:1070-8.
78. Kimischke A, Kemper DE, Castel MA, et al. Testosterone levels in men with chronic obstructive pulmonary disease with or without glucocorticoid therapy. Eur Respir J 1998;11:41-5.
79. Yeh SS, DeGuzman B, Kramer T. Reversal of COPD-associated weight loss using the anabolic agent oxandrolone. Chest 2002;122:421-8.
80. Inui A. Cancer anorexia-cachexia syndrome: current issues in research management. CA Cancer J Clin 2002;52:72-91.
81. Behan DP, Grigoriadis DE, Lovenberg T, et al. Neurobiology of corticotrophin releasing factor (CRF) receptors and CRF-binding protein: implications for the treatment of CNS disorders. Mol Psychiatry 1996;1:265-77.
82. Ramos EJ, Suzuki S, Marks D, Inui A, Asakawa A, Meguid MM. Cancer anorexia-cachexia syndrome: cytokines and neuropeptides. Curr Opin Clin Nutr Metab Care 2004;7:427-34.
83. Davis MP, Dreicer R, Walsh D, Lagman R, LeGrand SB. Appetite and cancer-associated anorexia: a review. J Clin Oncol 2004;22:1510-7.
84. Russell ST, Zimmerman TP, Domin BA, Tisdale MJ. Induction of lipolysis in vitro and loss of body fat in vivo by zinc alpha2-glycoprotein. Biochim Biophys Acta 2004;1636:59-68.
85. Jatoi A, Rowland K, Loprinzi CL, et al. An eicosapentaenoic acid supplement versus megestrol acetate versus both for patients with cancer-associated wasting: a North Central Cancer Treatment Group and National Cancer Institute Canada collaborative effort. J Clin Oncol 2004;22:2469-76.
86. Grobbelaar EJ, Owen S, Torrance AD, Wilson JA. Nutritional challenges in head and neck cancer. Clin Otolaryngol Allied Sci 2004;29:307-13.
87. Argiles JM, Almendro V, Busquets S, Lopez-Soriano FJ. The pharmacological treatment of cachexia. Curr Drug Targets 2004;5:265-77.
88. Jatoi A, Windschitl HE, Loprinzi CL, et al. Dronabinol versus megestrol acetate versus combination therapy cancer-associated anorexia: a North Central Cancer Treatment Group study. J Clin Oncol 2002;20:2912-3.
89. Jho D, Babcock TA, Helton WS, Espat NJ. Omega-3 fatty acids: implications for the treatment of tumor-associated inflammation. Am Surg 2003;69:32-6.
90. Tisdale MJ. The 'cancer cachectic factor.' Support Care Cancer 2003;11:73-78.
91. Bruera E, Strasser F, Palmer JL, et al. Effect of fish oil on appetite and other symptoms in patients with advanced cancer and anorexia/cachexia: a double-blind, placebo-controlled study. J Clin Oncol 2003;21:129-34.
92. Fearon KC, von Meyenfeldt MF, Moses AAG, et al. Effect of a protein and energy dense n-3 fatty acid enriched oral supplement on loss of weight and lean tissue in cancer cachexia: a randomized double blind trial. Gut 2003;52:1479-86.
93. Jatoi A, Jett JR, Sloan J, et al. A pilot study on safety and pharmacokinetics of infliximab for the cancer anorexia/weight loss syndrome in non-small-cell lung cancer patients. Support Care Cancer 2004;12:859-63.
94. Roubenoff R, Roubenoff RA, Cannon JG, et al. Rheumatoid cachexia: cytokine-driven hypermetabolism accompanying reduced body cell mass in chronic inflammation. J Clin Invest 1994;93:2379-86.
95. Walsmith J, Abad L, Kehayias J, Roubenoff R. Tumor necrosis factor-alpha production is associated with less body cell mass in women with rheumatoid arthritis. J Rheumatol 2004;31:23-9.
96. De Carvalho MRP, Tebexreni AS, Salles CAF, Neto TLB, Natour J. Oxygen uptake during walking in patients with rheumatoid arthritis - a controlled study. J Rheumatol 2004;31:655-62.
97. Roubenoff R, Walsmith J, Lundgren N, Snydman L, Dolnikowski GJ, Roberts S. Low physical activity reduces total energy expenditure in women with rheumatoid arthritis: implications for dietary intake recommendations. Am J Clin Nutr 2002;76:774-9.
98. Grunfeld C, Feingold KR. Metabolic disturbances and wasting in the acquired immunodeficiency syndrome. N Engl J Med 1992;327:329-37.
99. Eastgate JA, Wood NC, DiGiovine FS, Symons JA, Grinlinton FM, Duff GW. Correlation of plasma interleukin-1 levels with disease activity in rheumatoid arthritis. Lancet 1988;2:706-9.
100. Saxne T, Palladino MA, Heinegard D, Talal N, Wollheim FA. Detection of tumor necrosis factor-alpha but not tumor necrosis factor-beta in rheumatoid arthritis synovial fluid and serum. Arthritis Rheum 1988;31:1041-4.
101. Roubenoff R, Roubenoff RA, Ward LM, Stevens MB. Catabolic effects of high-dose corticosteroids persist despite therapeutic benefit in rheumatoid arthritis. Am J Clin Nutr 1990;52:1113-7.
102. Grinspoon S, Mulligan K. Weight loss and wasting in patients infected with human immunodeficiency virus. Clin Infect Dis 2003;236(suppl):S69-78.
103. Rodolphe T, Denis M, Catherine M, Francois D. Anthropometric indices as predictors of survival in AIDS adults. Aquitaine Cohort, France, 1985-1997. Eur J Epidemiol 2000;16:633-9.
104. Dolan S, Wilkie S, Aliabadi N, et al. Effects of testosterone administration in human immunodeficiency virus-infected women with low weight - a randomized placebo-controlled study. Arch Intern Med 2004;164:897-904.
105. Rietschel P, Corcoran C. Stanley T, Basgoz N, Klibanski A, Grinspoon S. Prevalence of hypogonadism among men with weight loss related to human immunodeficiency virus infection who were receiving highly active antiretroviral therapy. Clin Infect Dis 2000;31:1240-4.
106. Gonzalez-Cadavid NF, Taylor WE, Yarasheski K, et al. Organization of the human myostatin gene and expression in healthy men and HIV-infected men with muscle wasting. Proc Natl Acad Sci U S A 1998;95:14938-43.
107. Grinspoon S, Corcoran C, Parlman K, et al. Effects of testosterone and progressive resistance training in eugonadal men with AIDS wasting - a randomized, controlled trial. Ann Intern Med 2000;133:348-55.
108. Bhasin S, Storer TW, Javanbakht M, et al. Testosterone replacement and resistance exercise in HIV-infected men with weight loss and low testosterone levels. JAMA 2000;283:763-70.
109. Cominelli S, Raguso CA, Karsegard L, et al. Weight-losing HIV-infected patients on recombinant human growth hormone for 12 weeks: a national study. Nutrition 2002;18:583-6.
110. Moyle GJ, Daar ES, Gertner JM, et al. Growth hormone improves lean body mass, physical performance, and quality of life in subjects with HIV-associated weight loss or wasting on highly active antiretroviral therapy. J Acquir Immune Defic Syndr 2004;35:367-75.
111. Gelato MC, Mynarcik D, McNurlan MA. Soluble tumour necrosis factor alpha receptor 2, a serum marker of resistance of the anabolic actions of growth hormone in subjects with HIV disease. Clin Sci 2002;102:85-90.
112. Von Roenn JH, Armstrong D, Kotler DP, et al. Megestrol acetate in patients with AIDS-related cachexia. Ann Intern Med 1994;121:393-9.
113. Timpone JG, Wright DJ, Li N, et al. The safety and pharmacokinetics of single-agent and combination therapy with megestrol acetate and dronabinol for the treatment of HIV wasting syndrome. The DATRI 004 Study Group. Division of AIDS Treatment Research Initiative. AIDS Res Hum Retroviruses 1997;13:305-15.
114. Mwamburi DM, Gerrior JL, Wilson IB, et al. Comparing megestrol acetate therapy with oxandrolone therapy for HIV-related weight loss: similar results in 2 months. Clin Infect Dis 2004;38:895-902.
115. Liu L, Bopp MM, Roberson PK, Sullivan DH. Undernutrition and risk of mortality in elderly patients within 1 year of hospital discharge. J Gerontol Med Sci 2002;57A:M741-6.
116. Sullivan DH, Walls RC. Protein-energy undernutrition and the risk of mortality within six years of hospital discharge. J Am Coll Nutr 1998;17:571-8.
117. Sullivan DH, Yamashita BD, Johnson LE, et al. The GAIN (Geriatric Anorexia Nutrition (Registry: The impact of appetite and weight on mortality in a long-term care population. J Nutr Health Aging 2002;6:275-81.
118. Powell-Tuck J, Hennessy EM. A comparison of mid upper arm circumference, body mass index and weight loss as indices of undernutrition in acutely hospitalized patients. Clin Nutr 2003;22:307-12.
119. Bruunsgaard H, Andersen-Ranberg K, Jeune B, et al. A high plasma concentration of TNF-[alpha] is associated with dementia in centenarians. J Gerontol Med Sci 1999;54A:M357-64.
120. Dobbs RJ, Charlett A, Purkiss AG, et al. Association of circulating TNF-alpha and IL-6 with ageing and Parkinsonism. Acta Neurol Scand 1999;100:34-41.
121. Kania DM, Binkley N, Checovich M, Havighurst T, Schilling, Ershler WB. Elevated plasma levels of interleukin-6 in postmenopausal women do not correlate with bone density. J Am Geriatr Soc 1995;43:236-9.
122. Cohen HJ, Pieper CF, Harris T, et al. The association of plasma IL-6 levels with functional disability in community dwelling elderly. J Gerontol Med Sci 1997;52:M201-8.
123. Catania A, Airaghi L, Motta P, et al. Cytokine antagonists in aged subjects and their relation with cellular immunity. J Gerontol Biol Sci 1997;52:B93-7.
124. Larsson H, Elmstahl S, Gerglund G, Ahren B. Evidence for leptin regulation of food intake in humans. J Clin Endocrinol Metab 1998;83:4382-5.
125. Morley JE, Kumar VB, Mattammal MB, Farr S, Morley PM, Flood JF. Inhibition of feeding by a nitric oxide synthase inhibitor: effects of aging. Eur J Pharmacol 1996;311:15-9.
126. Morley JE, Alshaher MM, Farr SA, Flood JF, Kumar VB. Leptin and neuropeptide Y (NPY) modulate nitric oxide synthase: further evidence for a role of nitric oxide in feeding. Peptides 1999;20:595-600.
127. Morley JE, Flood JF. Evidence that nitric oxide modulates food intake in mice. Life Sci 1991;49:707-11.
128. Morley JE. Anorexia and weight loss in older persons. J Gerontol Med Sci 2003;58:131-7.
129. Chapman IM, MacIntosh CG, Morley JE, Horowitz M. The anorexia of ageing. Biogerontology 2002;3:67-71.
130. Wilson MM, Vaswani S, Liu D, Morley JE, Miller DK. Prevalence and causes of undernutrition in medical outpatients. Am J Med 1998;104:56-63.
131. Morley JE, Kraenzle D. Causes of weight loss in a community nursing home. J Am Geriatr Soc 1994;42:583-5.
132. Bosley BN, Weiner DK, Rudy TE, Granieri E. Is chronic nonmalignant pain associated with decreased appetite in older adults? Preliminary evidence. J Am Geriatr Soc 2004;52:247-51.
133. Teno JM, Kabumoto G, Wetle T, Roy J, Mor V. Daily pain that was excruciating at some time in the previous week: prevalence, characteristics, and outcomes in nursing home residents. J Am Geriatr Soc 2004;52:762-7.
134. Milne AC, Potter J, Avenell A. Protein and energy supplementation in elderly people at risk from malnutrition. Cochrane Database Syst Rev 2002;(3):CD003288.
135. Wilson MMG, Purushothaman R, Morley JE. Effect of liquid dietary supplements on energy intake in the elderly. Am J Clin Nutr 2002;75:944-7.
136. Meier DE, Ahronheim JC, Morris J, Baskin-Lyons S, Morrison RS. High short-term mortality in hospitalized patients with advanced dementia - lack of benefit of tube feeding. Arch Intern Med 2001;161:594-9.
137. Tokuda Y, Koketsu H. High mortality in hospitalized elderly patients with feeding tube placement. Intern Med 2002;41:613-6.
138. Abuksis G, Mor M, Plaut S, Fraser G, Niv Y. Outcome of percutaneous endoscopic gastrostomy (PEG): comparison of two policies in a 4-year experience. Clin Nutr 2004;23:341-6.
139. Sherman FT. Nutrition in advanced dementia -tube-feeding or hand-feeding until death? Geriatrics 2003;58:10-12.
140. Klose J, Heldwein W, Rafferzeder M, Sernetz F, Gross M, Loeschke K. Nutritional status and quality of life in patients with percutaneous endoscopic gastrostomy (PEG) in practice - prospective one-year follow-up. Dig Dis Sci 2003;48:2057-63.
141. Teasell R, Foley N, McRae M, Finestone H. Use of percutaneous gastrojejunostomy feeding tubes in the rehabilitation of stroke patients. Arch Phys Med Rehabil 2001;82:1412-5.
142. Yeh SS, Wu SY, Lee TP, et al. Improvement in quality-of-life measures and stimulation of weight gain after treatment with megestrol acetate oral suspension in geriatric cachexia: results of a double-blind, placebo-controlled study. J Am Geriatr Soc 2000;48:485-92.
143. Morley JE. Orexigenic and anabolic agents. Clin Geriatr Med 2002;18:853-66.