The pharmacologic approach to the treatment of obesity

Journal of Clinical Pharmacology

Volumn 37, Issue 6, 1997, Pages 453-473

  Weiser, Mitchell ^a   Frishman, William H ^a   Michaelson, M Dror ^a   Abdeen, M Anwar ^a  

^a ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 [2 [(2 HYDROXY 2 PHENYLETHYL)AMINO]PROPYL]BENZOIC ACID METHYL ESTER HYDROGEN MALEATE; 4 [2 [[2 (3 CHLOROPHENYL) 2 HYDROXYETHYL]AMINO]PROPYL]PHENOXYACETIC ACID METHYL ESTER; 5 [2 [[2 (3 CHLOROPHENYL) 2 HYDROXYETHYL]AMINO]PROPYL] 1,3 BENZODIOXOLE 2,2 DICARBOXYLIC ACID; ADRENERGIC RECEPTOR STIMULATING AGENT; AMFEPRAMONE; AMYLIN; ANOREXIGENIC AGENT; BETA 3 ADRENERGIC RECEPTOR STIMULATING AGENT; BOMBESIN; CATECHOLAMINE; CHOLECYSTOKININ; CORTICOTROPIN RELEASING FACTOR; DEXFENFLURAMINE; ENTEROSTATIN; FENFLURAMINE; FLUOXETINE; GLUCAGON LIKE PEPTIDE 1; LEPTIN; MAZINDOL; NEUROPEPTIDE; NEUROPEPTIDE Y; PHENTERMINE; PHENYLPROPANOLAMINE; PLACEBO; RO 16 8174; RO 40 2148; SEROTONIN; SIBUTRAMINE; TETRAHYDROLIPSTATIN; UNCLASSIFIED DRUG; UNINDEXED DRUG;

CARDIOVASCULAR DISEASE; CLINICAL TRIAL; DIABETES MELLITUS; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG HALF LIFE; DRUG MECHANISM; ENERGY EXPENDITURE; GASTROINTESTINAL TOXICITY; HUMAN; HYPERTENSION; NEUROTOXICITY; OBESITY; ORAL DRUG ADMINISTRATION; REVIEW; THERMOGENESIS;

EID: 0030953225     PISSN: 00912700     EISSN: None     Source Type: Journal    
DOI: 10.1002/j.1552-4604.1997.tb04323.x     Document Type: Review

References (259)

1. McGinnis JM, Forge WH: Actual causes of death in the United states. JAMA 1993;270:2207-2212.
2. Kuczmarski RJ, Flegal KM, Campbell SM, Johnson CL: Increasing prevalence of overweight among U.S. adults: the National Health and Nutrition Examination Surveys 1960 to 1991. JAMA 1994;272:205-211.
3. Anderson KM, Kannel WB: Obesity and disease. In, Bjorntorp P, Brodoff BN (eds.): Obesity. New York: JB Lippincott, 1992;465-473.
4. 1983 Metropolitan Height and Weight Tables Statistical Bulletin. Metropolitan Life Insurance Company 1983;64:1.
5. National Center for Health Statistics: Plan and Operation of the National Health and Nutrition Examination Survey, 1976-80. Washington DC: US Public Health Service; 1981. DHHS publication (PHS) 81-1317 (Vital and Health Statistics, Series 1, no 15).
6. Van Itallie TB: Health implications of overweight and obesity in the United States. Ann Intern Med 1985;103:983.
7. Pi Sunyer FX: Medical hazards of obesity. Ann Intern Med 1993;119:655-660.
8. Stamler R, Stamler J, Riedlinger WF, Algera G, Roberts RH: Weight and blood pressure: findings in hypertension screening of 1 million Americans. JAMA 1978;240:1607-1610.
9. Boe J, Humerfelt S, Wederrang G: The blood pressure in a population: blood pressure readings and height and weight determinations in the adult population of the city of Bergen. Acta Med Scand 1957;157(suppl 321):1-336.
10. Epstein FH, Francis T, Hayner NS, Johnson BC, Kjelsberg MO, Napier JA, et al: Prevalence of chronic diseases and distribution of selected physiologic variables in a total community, Tecumsch, Michigan. Am J Epidemiol 1965;81:307-322.
11. MacMahon SW, Blacket RB, MacDonald Gf, Hall W: Obesity, alcohol consumption and blood pressure in Australian men and women: The National Heart Foundation of Australia Risk Factor Prevalence Study. J Hypertens 1984;2:85-91.
12. Brenner BM, Garcia DL, Anderson S: Glomeruli and blood pressure: less of one more of another? Am J Hypertens 1988;1:355-357.
13. Reisin E, Messerli FG, Ventura HO: Renal hemodynamic studies in obesity hypertension. J Hypertens 1987;5:397.
14. DeFronzo RA, Cooke CR, Andres R, Faloona GR, Davis PJ: The effect of insulin on renal handling of sodium, potassium, calcium and phosphate in man. J Clin Invest 1975;55:845-855.
15. Dornfeld LP, Maxwell MH, Waks A, Tuck M: Mechanisms of hypertension in obesity. Kidney Int Suppl 1987;22:S254-S258.
16. Glueck CJ, Taylor HL, Jacobs D, Morrison JA, Beaglehole R, Williams OD: Plasma high-density lipoprotein cholesterol: association with measurements of body mass. The Lipid Research Clinical Program Prevalence Study. Circulation 1980;62(suppl IV):IV-62-IV-69.
17. Montoye JE, Epstein FH, Kjelsberg MO: Relationship between serum cholesterol and body fatness: an epidemiologic study. Am J Clin Nutr 1966;18:397-406.
18. Assman G, Schult H: Obesity and hyperlipidemia: results from the prospective cardiovascular Munster (PROCAM) Study. In, Bjorntorp P, Brodoff BN (eds.): Obesity. New York: JB Lippincott, 1992;502-511.
19. Kannel WB, Gordon T: Physiological and medical concomitants of obesity: the Framingham Study. In, Bray G (ed.): Obesity in America. Bethesda, MD: US Dept of Health, Education, and Welfare, Public Health, Health Service, National Institutes of Health; 1979;125-163.
20. Farinaro E, Cortese C, Rubba P, DiMarino L, Mancini M: Overweight and plasma lipoprotein abnormalities in a random sample of the Neapolitan population. In, Mancini M, Lewis B, Contaldo F (eds.): Medical Complications of Obesity. London: Academic Press, 1979;143-150.
21. Albrink MJ, Meigs JW, Granoff MA: Weight gain and serum triglycerides in normal men. N Engl J Med 1962;266:484-489.
22. Knowler WC, Pettitt DI, Savage PJ, Bennett PH: Diabetes incidence in Pima Indians: contributions of obesity and parental diabetes. Am J Epidemiol 1981;113:144-156.
23. Colditz GA, Willett WC, Rotnitzky A, Manson JE: Weight gain as a risk factor for clinical diabetes mellitus in women. Ann Intern Med 1995;122:481.
24. United States National Commission on Diabetes: Report of the National Commission on Diabetes to the Congress of the United States. Bethesda, MD: US Dept of Health, Education, and Welfare publication no. 76-1021, vol 1; 1975.
25. Bierman EL, Bagdade JD, Porte D Jr: Obesity and diabetes: the odd couple. Am J Clin Nutr 1968;21:1434-1437.
26. Ward WK, Johnston C, Beard JC, Benedetti TJ, Halter JB, Porte D Jr: Abnormal fat distribution in subjects predisposed to NIDDM (abstract). Clin Res 1985;33:67A.
27. Olefsky JM: The insulin receptor; its role in insulin resistance of obesity and diabetes. Diabetes 1976;25:1154.
28. Manson JE, Colditz GA, Stampfer MJ, Willett WC, Rosner B, Monson RR, et al: A prospective study of obesity and risk of coronary heart disease in women. N Engl J Med 1990;322:882-889.
29. Council on Scientific Affairs of the American Medical Association: Treatment of obesity in adults. JAMA 1988;260:2547-2551.
30. Donahue RP, Abbott RD, Bloom E, Reed DM, Yano K: Central obesity and coronary heart disease in men. Lancet 1987;1:821-824.
31. Lapidus L, Bengtsson C, Larsson BO, Pennart K, Rybo E, Sjostrom L: Distribution of adipose tissue and risk of cardiovascular disease and death: a 12 year follow-up of participants in the population study of women in Gothenburg, Sweden. BMJ 1984; 289:1257-1261.
32. Burnett W: The epidemiology of gallstones. Tijdschr Gastroenterol 1971;14:79-89.
33. Sharp JT, Barrocas M, Chokroverty S: The cardiorespiratory effects of obesity. Clin Chest Med 1980;1:103-108.
34. Goldin RH, McAdam L, Louis JS, Gold R, Bluestone R: Clinical and radiologic survey of the incidence uf osteoarthritis among obese patients. Ann Rheum Dis 1976;35:349-353.
35. Sidney S, Friedman GD, Siegelaub AB: Thinness and mortality. Am J Public Health 1987;77:317-322.
36. Kral JG: Morbid obesity and related health risks. Ann Intern Med 1985;103:1043-1047.
37. Van Itallie TB: Obesity: adverse effects on health and longevity. Am J Clin Nutr 1979;32:2723-2733.
38. Lee IM, Manson JE, Hennekens CH, Paffenbarger RS: Body weight and mortality: a 27 year follow-up of middle-aged men. JAMA 1993;270:2823-2828.
39. Manson JE, Willett WC, Stampfer MJ, Colditz GA, Hunter DJ, Hankinson SE, et al: Body weight and mortality among women. N Engl J Med 1995;333:677-685.
40. Bjorntorp P: Classification of obese patients and the complications related to the distribution of surplus fat. Am J Clin Nutr 1987;45:1120-1125.
41. Stunkard AJ: Current views on obesity. Am J Med 1996; 100:230-236.
42. Sjostrom L: Impacts of body weight, body composition and adipose tissue distribution on morbidity and mortality. In, Stunkard AJ, Wadden TA (eds.): Obesity: Theory and Therapy. Second Edition. Philadelphia: Lippincott-Raven, 1992;13.
43. Stark RET, Vash PD: Obesity. The Bariatrician 1992;summer:14.
44. National Institutes of Health: Consensus Development Conference Statement on health implicators of obesity. Ann Intern Med 1985;103:1073.
45. Goldstein DJ: Beneficial effects of moderate weight loss. Int J Obes 1992;16:397-415.
46. Wadden TA: Etiology and treatment of obesity. Curr Opin Psychiatry 1993;6:816-820.
47. Sobal J, Stunkard AJ: Socioeconomic status and obesity: a review of the literature. Psychol Bull 1989;105:260-275.
48. Bandini LJ, Schoeller DA, Cyr HYN, Dietz WH: Validity of reported energy intake in obese and non-obese adolescents. Am J Clin Nutr 1990;52:421-425.
49. Flatt JP, Ravussin E, Achescn KJ, Jequier E: Effects of dietary fat on postprandial substrate oxidation and on carbohydrate and fat balance. J Clin Invest 1985;76:1019-1024.
50. McGinnis JM: The public health burden of a sedentary life style. Med Sci Sport Exerc 1992;24:5196n5200.
51. Rose GA, Williams RT: Metabolic studies on large and small eaters. Br J Nutr 1961;15:1.
52. Ravussin E, Bogardus C: A brief overview of human energy, metabolism and its relationship to essential obesity. Am J Clin Nutr 1992;55:242S-245S.
53. Miller DS, Mumford PM: Gluttony: parts I and II. Am J Clin Nutr 1967;20:1212-1223.
54. Simms EAH, Horton ES: Endocrine and metabolic adaptation to obesity and starvation. Am J Clin Nutr 1968;21:1455.
55. Garrow JS: Energy Balance and Obesity in Man. Amsterdam: Elsevier/North-Holland Biomedical Press, 1978.
56. Jequier E: Does a thermogenic defect play a role in the pathogenesis of human obesity? Clin Physiol 1983;3:1-7.
57. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM: Positional cloning of the mouse obese gene and its human homologue. Nature 1994;372:425-432.
58. Rohner-Jeanrenaud F, Jeanrenaud B: Obesity, leptin and the brain. N Engl J Med 1996;334:324-325.
59. Weigle DS, Kuijpers JL: Mouse models of human obesity. Sci Med 1997;4137:38-45.
60. Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, et al: Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 1996;334:292-295.
61. Lee GH, Proenca R, Montez JM, Carroll KM, Darvishzadeh JG, Lee JI, Friedman JM: Abnormal splicing of the leptin receptor in diabetic mice. Nature 1996;379:632-635.
62. 3-adrenergic receptor and an increased capacity to gain weight in patients with morbid obesity. N Engl J Med 1995;333:352-354.
63. Mayer J: Genetic factors in human obesity. Ann N Y Acad Sci 1965;131:412-421.
64. Stunkard AJ, Harris JR, Pederson NL, McClearn GE: The body mass index of twins who have been reared apart. N Engl J Med 1990;322:1483-1487.
65. Withers RFJ: Problems in the genetics of human obesity. Eugenics Rev 1964;56:81.
66. Brodoff BN: Pharmacological Treatment of Obesity. American Health Consultants, 1995.
67. Lesses NF, Myerson A: Human autonomic pharmacology: benzedrine sulphate as an aid in treatment of obesity. N Engl J Med 1938;218:119.
68. Nathanson MH: The central action of beta-amino propylbenzene (Benzedrine): clinical observations. JAMA 1939;108:528.
69. Gold H: Clinical importance and uses. Ind Eng Chem 1945;37:117.
70. Silverston T: Appetite suppressants: a review. Drugs 1992; 43:820-336.
71. Wellman PJ: Overview of adrenergic anorectic agents. Am J Clin Nutr 1992;55:193S-198S.
72. Lasagna L: Anorectic activity. In. Phenylpropanolamine: A Review. New York: Wiley-Interscience, 1988;132-146.
73. Altschuler S, Frazer DL: Double-blind clinical evaluation of the anorectic activity of phenylpropanolamine hydrochloride drops and placebo drops in the treatment of exogenous obesity. Curr Ther Res 1986;40:211-217.
74. Greenway F: A double-blind clinical evaluation of the anorectic activity of phenylpropanolamine versus placebo. Clin Ther 1989;11:584-589.
75. Schteingart D: Effectiveness of phenylpropanolamine as an adjunct in the dietary management of obesity (abstract). Int J Obesity 1990;14(suppl 2):48.
76. Greenway FL: Clinical studies with phenylpropanolamine: a meta analysis. Am J Clin Nutr 1992;55:2035-2055.
77. Winick C: Phenylpropanolamine: toward resolution of a controversy editorial. J Clin Psychopharmacol 1991;11:79-81.
78. Morgan JP, Funderburk FR, Blackburn GL, Noble R: Subjective profile of phenylpropanolamine: absence of stimulant or euphorigenic effects at recommended dose levels. J Clin Psychopharmacol 1989;9:33-38.
79. Blackburn GL, Morgan JP, Lavin PT, Noble R, Funderburk FR, Istfan N: Determinants of the pressor effect of phenylpropanolamine in healthy subjects. JAMA 1989;261:3267-3272.
80. Bradley MH, Raines J: The effects of phenylpropanolamine hydrochloride in overweight patients with controlled stable hypertension. Curr Ther Res 1989;46:74-84.
81. Anonymous: Drugs used in obesity. AMA Drug Evaluations Annual. Chicago: American Medical Association, 1995;2439.
82. Advance notice of proposed role (ANPR) making for OTC weight control drug products (17-FR-8466, 8471, 8477) Feb 1982.
83. Letter from FDA to Non-prescription Drug Manufacturers Association. March 9, 1993.
84. Tuominen S, Hietola M, Kuusankoski M: Double-blind trial comparing fenfluramine, phenturmine and dietary advice on treatment of obesity. Int J Obes 1980;14(suppl 2):138.
85. Campbell C, Bhalla IP, Steel JM, Duncan LJP: A controlled trial of phentermine in obese patients. Practitioner 1977;218:851-855.
86. Douglas A, Douglas JG, Robertson CE, Monroe JF: Plasma phentermine levels, weight loss and side effects. Int J Obesity 1983;7(suppl 6):591-595.
87. Hoekenga MT, O'Dillon RH, Leyland HM: A comprehensive review of diethylpropion hydrochloride. In, Garattini S, Samanin R (eds.): Central Mechanisms of Anorectic Drugs. New York: Raven Press, 1978;391-404.
88. Allen GS: A double blind trial of diethylpropion hydrochloride, mazindol and placebo in the treatment of erogenous obesity. Curr Ther Res 1977;22:678-683.
89. Bolding OT: Diethylpropion hydrochloricle: an effective appetite suppressant. Curr Ther Res 1974;16:40-43.
90. Sullivan AC, Comai K: Pharmacological treatment of obesity. Int J Obes 1979;2:167-189.
91. Carabillo EA: USA drug abuse warning network. In, Garattini S, Samanin S (eds.): Central Mechanisms of Anorectic Drugs. New York: Raven Press, 1978;461.
92. Samanin R, Garattini S: Neuropharmacology of feeding. In, Silverstone T (ed.): Drugs and Appetite. London: Academic Press, 1982;23-39.
93. Silverstone T, Kyriakides M: Clinical pharmacology of appetite. In, Silverstone T (ed.): Drugs and Appetite. London: Academic Press, 1982;93-123.
94. Onishi T: Clinical evaluation of mazindol, an anorexiant on obesity. Int J Obes 1990;14(suppl 2):34.
95. Munro JF: The clinical use of anti-obesitv agents. In, Munro JF (ed.): The Treatment of Obesity. Lancaster: MTP, 1979:85-121.
96. Bradley MJ, Blum NJ, Scheib RK: Mazindol in obesity with known cardiac disease. J Int Med Res 1974;2:347-354.
97. Chait LD, Uhlenhuth EH, Johanson CE: Reinforcing and subjective effects of several anorectics on normal human volunteers. J Pharmacol Exp Ther 1987;242:777-783.
98. Wurtman R, Wurtman J: Serotonin and eating disorders (abstract). Presented at the Satellite Symposium at the 70th International Congress on Obesity on Pharmacologic Treatment of Obesity. Saint-Adede, Quebec, August 18-20, 1994;6.
99. Nathan C: Serotonin agonists. In, Bjornstorp P, Brodoff BN (eds.): Obesity. New York: JB Lippincott, 1992;751-761.
100. Goodall E, Silverston T: Differential effect of d-fenfluramine and metergoline on food intake in human subjects. Appetite 1988;11:215-228.
101. Angel I: Central receptors and recognition sites mediating the effects of monoamines and anorectic drugs on feeding behaviour. Clin Neuropharmacol 1990;13:361-391.
102. Goldstein DJ, Potvin JH: Long-term weight loss: the effect of pharmacologic agents. Am J Clin Nutr 1994;60:647-657.
103. Fink M, Shapiro DM, Itil TM: EEG profiles of fenfluramine, amobarbital and dextroamphetamine in normal volunteers. Psychopharmacologia 1971;22:369-383.
104. Turner P: Peripheral mechanisms of fenfluramine. Curr Med Res Opin 1979;6(suppl 1):101-106.
105. Campbell DB: Plasma concentration of fenfluramine and its metabolite, norfenfluramine following single and repeated oral administration. Br J Pharmacol 1971;43:465-469.
106. Silverstone JT, Fincham J, Campbell DB: The anorectic activity of fenfluramine. Postgrad Med J 1975;51(suppl 1):171-174.
107. Munro JF, Ford M: Drug treatment of obesity. In, Silverston T (ed.): Drugs and Appetite. London: Academic Press, 1982;125-157.
108. Weintraub M, Sriwatanakul K, Sundaresan PR, Weis OF, Dorn IM: Extended release fenfluramine: patient acceptance and efficacy of evening dose. Clin Pharmacol Ther 1983;33:621-627.
109. Bray GA: Use and abuse of appetite-suppressant drugs in the treatment of obesity. Ann Intern Med 1993;119:707.
110. Gagnon M, Bordileau J, Tetrault L: Fenfluramine: study of its central action through its effects on sleep. Int J Clin Pharmacol 1969;1:74-82.
111. Abenhaim L, Moride Y, Brenot F, Rich S, Benichou J, Kurz X, at al: Appetite suppresant drugs and the risk of primary pulmonary hypertension. N Engl J Med 1996;335:609-616.
112. Brenot F, Herve P, Petitpretz P, Parent F, Duroux P, Simonneau G: Primary pulmonary hypertension and fenfluramine use. Br Heart J 1993;70:537-541.
113. FDC Reports: Prescription pharmaceuticals and biotachnology. The Pink Sheet 1996;May 6:58.
114. Blundell JE, Lawton CL: Serotonin and dietary fat intake: effects of doxfenfluramine. Metabolism 1995;44(suppl 2);33-37.
115. Garattini S, Bizzi A, Caccia S, Mennini T, Samanin R: Progress in assessing the role of serotonin in the control of food intake. Clin Neuropharmacol 1988;11(suppl 1):528-532.
116. Garattini S, Mennini T, Bendotti C, Invernizzi R, Samanin R: Neurochemical mechanism of action of drugs which modify feeding via the serotinergic system. Appetite 1986;7(suppl):15-38.
117. Silverstone T: Appetite suppressants: a review. Drugs 1992; 43:820-836.
118. Dexfenfluramine: prescribing information. Philadelphia: Wyeth Laboratories, April 29, 1996.
119. Spedding M, Ouvry C, Millan M, Duhault J, Dacquet C, Wurtman R: Neural control of dieting. Nature 1996;380:488.
120. Leibowitz SF, Weiss GF, Shor-Posner G: Hypothalmic serotonin: pharmacological, biochemical and behavioral analyses of its feeding-suppressive action. Clin Neuropharmacol 1988; 11(suppl 1):S51-S71.
121. Andersson B, Zimmermann ME, Hedner T, Bjorntorp P: Haemodynamic, metabolic and endocrine effects of short-term dexfenfluramine treatment in young, obese women. Eur J Clin Pharmacol 1991;40:249-254.
122. O'Connor HT, Richman RM, Steinbeck KS, Caterson ID: Doxfenfluramine treatment of obesity: a double-blind trial with post trial follow up. Int J Obes Relat Metab Disord 1995;19:180-189.
123. Scheen AJ, Paolisso G, Salvatore T, Lefebvre PJ: Improvement of insulin-induced glucose disposal in obese patients with NIDDM after 1 week treatment with d-fenfluramine. Diabetes Care 1991;14:325-332.
124. Samanin R, Neill JC, Grignaschi G, Padura IM, Bizzi A: Role of 5-HT receptors in the effect of d-fenfluramine on gastric emptying and feeding behavior as examined in the runway test. Eur J Pharmacol 1991;197:69-73.
125. Goodall E, Corney R, Stanton R, Browne PB: Changes in food preference in premenstrual syndrome. Presented at the First European Congress on Obesity, Stockholm, 1988.
126. Wurtman J, Wurtman R, Reynolds S, Tsay R, Chew B: Fenfluramine suppresses snack intake among carbohydrate cravers but not among non-carbohydrate cravers. Int J Eat Disord 1987;6:687-699.
127. Wurtman JJ, Wurtman RJ: D-fenfluramine selectively decreases carbohydrate but not protein intake in obese subjects. Int J Obes 1984;8(suppl 1):79-84.
128. Bernstein JG: Management of psychotropic drug-induced obesity. In, Brodoff BN, Bleicher SJ (eds.): Diabetes Mellitus and Obesity. Baltimore: Williams and Wilkins, 1982;445.
129. Owens CA, Chow MS: Focus on dexfenfluramine: a serotonin reuptake inhibitor for the management of obesity. Formulary 1996;31:659-669.
130. Levitsky DA, Stallone D: Enhancement of the thermic effect of food by d-fenfluramine. Clin Neuropharmacol 1988;11(suppl 1):S90-S92.
131. Breum L, Astrup A, Andersen T, Lammert O, Nielsen E, Garby L, Quaade F: The effect of long-term dexfenfluramine treatment on 24-hour energy expenditure in man: a double blind placebo controlled study. Int J Obes 1990;14:613-621.
132. Anonymous: Dexfenfluramine for obesity. Med Lett 1996:38(979):64-65.
133. Finer N, Craddock D, Lavielle R: Dexfenfluramine in the treatment of refractory obesity. Curr Ther Res 1985;38:847-854.
134. Finer N, Craddock D, Lavielle R, Keen H: Effect of 6 months therapy with dexfenfluramine in obese patients: studies in the United Kingdom. Clin Neuropharmacol 1988;11(suppl 1):S179-S186.
135. Enzi G, Crepaldi G, Inelmen EM, Bruni R, Baggio B: Efficacy and safety of dexfenfluramine in obese patients: a multicenter study. Clin Neuropharmacol 1988;(suppl 1):S173-S178.
136. Lucas CP, Sandage BW: Treatment of obese patients with dexfenfluramine: a multicenter, placebo-controlled study. Am J Ther 1995;2:962-967.
137. Finer N, Finer S, Naoumova RP: Prolonged use of a very low calorie diet (Cambridge Diet) in massively obese patients attending an obesity clinic: safety, efficacy and additional benefit from dexfenfluramine. Int J Obes 1989:13(suppl 2):91-93.
138. Guy-Grand B, Apfelbaum M, Crepaldi G, Gries A, Lefebvre P, Turner P: International trial of long-term dexfenfluramine in obesity. Lancet 1989;2:1142-1144.
139. Noble RE: A six-month study of the effects of dexfenfluramine on partially successful dieters. Curr Ther Res 1990;47:612-619.
140. Mathus-Vliegen EMH, Van De Voorde K, Kok AME, Res AMA: Dexfenfluramine in the treatment of severe obesity: a placebo-controlled investigation of the effects of weight loss, cardiovascular risk factors, food intake and eating behavior. J Intern Med 1992;232:119-127.
141. Turner P: Dexfenfluramine: its place in weight control. Drugs 1990;39(suppl 3):53-62.
142. Anonymous: FDA news and product notes. Formulary 1996;31:552.
143. McTavish D, Heel RC: Dexfenfluramine: a review of its pharmacological properties and therapeutic potential in obesity. Drugs 1992;43:713-733.
144. Toornvliet AC, Pijl H, Meinders AE: Major depression during dexfenfluramine treatment (letter). Int J Obes 1994;18:650.
145. Dexfenfluramine: Formulary service information form. Philadelphia: Wyeth Laboratories, May 1996.
146. Anonymous: Fluoxetine (Prozac) and other drugs for treatment of obesity. Med Lett 1994;36(936):107-108.
147. McGuirk J, Silverstone T: The effects of 5-HT reuptake inhibitor fluoxetine on food intake and body weight in healthy male subjects. Int J Obes 1990;14:361-372.
148. McGuirk J, Silverstone T: Effects of fluxetine on appetite, food intake and body weight in obese subjects. Int J Obes 1990;14(suppl 2):141.
149. Levine LR, EnaS GG, Thompson WL, Byyny RL, Dauer AD, Kirby RW, et al: Use of fluoxetine in the treatment of obesity. Int J Obes 1989;13:635-645.
150. Ferguson JM, Feighner JP: Fluxetine induced weight loss in overweight non depressed subjects. Int J Obes 1987;11(suppl 3):163-170.
151. Chiasson JL, Lau DCW, Leiter LA, Tildesley HD, Birmingham CL, Eoke JM, et al: Fluoxetine has potential in obese NIDDM-Multicenter Canadian trial (abstract). Diabetes 1989;38(suppl 2):154.
152. Fernandez-Soto ML, Gonzalez-Jimenez A, Barredo-Acedo F, Luna del Castillo JD, Escobar-Jimenez F: Comparison of fluoxetine and placebo in the treatment of obesity. Ann Nutr Metab 1995;39(3):159-163.
153. Goldstein DJ, Rampey AH Jr, Enas GG, Potvin JH, Fludzinski LA, Levine LR: Fluoxetine: a randomized clinical trial in the treatment of obesity. Int J Obes Relat Metab Disord 1994;18:129-135.
154. Marcus MD, Wing RR, Ewing L, Kern E, McDermott M: A double blind placebo controlled trial of fluoxetine plus behavior modification in the treatment of obese binge-eaters and non-binge-eaters. Am J Psychiatry 1990;147:876-881.
155. Kutnowski M, Daubresse J, Friedman H, Kolanowski J, Krzentowski G: Eight weeks fluoxetine therapy in obese patients with impaired glucose tolerance. Int J Obes 1990;14(suppl 2):48.
156. Steel JM, Munro JF, Duncan LJP: A comparative trial of different regimens of fenfluramine and phentermine in obesity. Practitioner 1973;211:232-236.
157. Weintraub M, Sundaresan PR, Madan M, Schuster B, Balder A, Lasagna L, Cox C: Long-term weigt control study I (weeks 0-34): the enhancement of behavior modification, caloric restriction, and exercise by fenfluramine plus phentermine versus placebo. Clin Pharmacol Ther 1992;51:586-596.
158. Sullivan AC, Triscari J, Comai K: Pharmacological modulation of lipid metabolism for the treatment of obesity. Int J Obes 1984;8(suppl 1):241-248.
159. Arch JRS, Ainsworth AT, Cawthorne MA, Piercy V, Sennitt MV, Thody VE, et al: Atypical β-adrenoceptor on brown adipocytes as target for anti-obesity drugs. Nature 1984;309:163-165.
160. Wilson C, Wilson S, Piercy V, Sennitt MV, Arch JRS: The rat lipolytic β-adrenoceptor: studies using novel β-adrenoceptor agonists. Eur J Pharmacol 1984;100:309-319.
161. Emorine LJ, Marullo S, Briend-Sutren MM, Patey G, Tate K, Delavier-Klutchko C, Strosberg AD: Molecular characterization of the human β3-adrenergic receptor. Science 1989;245:1118-1121.
162. Nahmias C, Blin N, Elalouf JM, Mattei MG, Strosberg AD, Emorine LJ: Molecular characterization of the mouse β3-adrenergic receptor: relationship with the atypical receptor of adipocytes. EMBO J 1991;10:3721-3727.
163. Granneman JG, Lahners KN, Chaudhry A: Molecular cloning and expression of the rat β3-adrenergic receptor. Mol Pharmacol 1991;40:895-899.
164. Giacobino JP: β3-adrenoceptor: an update. Eur J Endocrinol 1995;132:377-385.
165. Goldberg DE, Frishman WH: Beta3-Adrenergic Agonism: A New Concept in Human Pharmacotherapy. New York: Futura, 1995.
166. Trayhurn P: Brown adipose tissue and energy balance. In, Trayburn P, Nicholls DG (eds.): Brown Adipose Tissue. London: Edward Arnold, 1986;299-338.
167. Himms-Hagen J: Brown adipose tissue thermogenesis and obesity. Prog Lipid Res 1989;28:67-115.
168. Lowell BB, S-Susulic V, Hamann A, Lawitts JA, Himms-Hagen J, Boyer BB, et al: Development of obesity in transgenic mice after genetic ablation of brown adipose tissue. Nature 1993;366:740-742.
169. Hoffstedt J, Shimizu M, Sjostedt S, Lonnqvist F: Determination of beta 3-adrenoceptor mediated lipolysis in human fat cells. Obes Res 1995;3:447-457.
170. Klaus S, Casteilla L, Bouillaud F, Ricquier D: The uncoupling protein UCP: a membraneous mitochondrial ion carrier exclusively expressed in brown adipose tissue. Int J Biochem 1991;23:791-801.
171. Krief S, Lonnqvist F, Raimbault S, Baude B, Van Spronsen A, Arner P, et al: Tissue distribution of β3-adrenergic receptor mRNA in man. J Clin Invest 1993;91:344-349.
172. Liu YL, Toubru S, Astrup A, Stock MJ: Contribution of the beta 3-adrenoceptor activation to ephedrine-induced thermogenesis in humans. Int J Obes Relat Metab Disord 1995;19:678-685.
173. Walston J, Silver K, Bogardus C, Knowler WC, Celi FS, Austin S, et al: Time of onset of non-insulin-dependent diabetes mellitus and genetic variation in the β3-adrenergic-receptor gene. N Engl J Med 1995;333:343-347.
174. Widen E, Lehto M, Kanninen T, Walston J, Shuldiner AR, Groop LC: Association of a polymorphism in the β3-adrenergic-receptor gene with features of the insulin resistance syndrome in Finns. N Engl J Med 1995;333:348-351.
175. Carpene C, Galitzky J, Collon P, Esclapez F, Dauzats M, Lafontan M: Desensitization nf beta 1- and beta 2-but not beta 3-adrenoceptor-mediated lipolytic responses of adipocytes after long-term epinephrine infusion. J Pharmacol Exp Ther 1993; 265:237-247.
176. Nantel F, Bonin H, Emorine LJ, Zilberfarb V, Strosberg AD, Bouvier M, Marullo S: The human beta 3-adrenergic receptor is resistant to short term agonist-promoted desensitization. Mol Pharmacol 1993;43:548-555.
177. Nantel F, Bouvier M, Strosberg AD, Marullo S: Functional effects of long-term activation on human beta 2-and beta 3-adrenoceptor signalling. Br J Pharmacol 1995;114:1045-1051.
178. Thomas RF, Holt BD, Schwinn DA, Liggett SB: Long-term agonist exposure induces upregulation of beta 3-adrenergic receptor expression via multiple cAMP response elements. Proc Natl Acad Sci U S A 1992;89:4490-4494.
179. Wilson C, Pettinger SJ, Hayward J, Birtles S, Holloway BR: Cardiovascular effects of the thermogenic beta-adrenoceptor agonist, ICI D7114, in conscious telemetred dogs. Br J Pharmacol 1992;105:234P.
180. Gainer JL, Briscoe MG, Holloway BR: The effects of thermogenic agents on hindlimb oxygen consumption in the dog: ICI D7114 and noradrenaline. Experientia 1993;49:68-72.
181. Tavernier G, Galitzky J, Bousquet-Melou A, Montastruc JL, Berlan M: The positive chronotropic effect induced by BRL 37344 and CGP 12177, two beta-3 adrenergic agonists, does not involve cardiac beta adrenoceptors but baroreflex mechanisms. J Pharmacol Exp Ther 1992;263:1083-1090.
182. Gauthier C, Tavernier G, Charpentier F, Langin D, Le Marec H: Functional β3-adrenoceptor in the human heart. J Clin Invest 1996;98:556-562.
183. Connacher AA, Bennet WM, Jung RT: Clinical studies with the β-adrenoceptor agonist BRL 26830A. Am J Clin Nutr 1992; 55(suppl):258S-261S.
184. Cawthorne MA, Sennitt MB, Arch JRS, Smith SA: BRL 35135, a potent and selective atypical β-adrenoceptor agonist. Am J Clin Nutr 1992;55(suppl):252S-255S.
185. Jaquier E, Munger R, Felber JP: Thermogenic effects of various β-adrenoceptor agonists in humans: their potential usefulness in the treatment of obesity. Am J Clin Nutr 1992;55(suppl):249S-251S.
186. Bloom JD, Dutia MD, Johnson BD, Wissner A, Burns MG, Largis EE, et al: Disodium (R,R)-5-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl] amino]propyl]-1,3-benzodioxole-2,2-dicarboxylate (CL 316,243): a potent beta-adrenergic agonist virtually specific for beta 3 receptors. A promising antidiabetic and antiobesity agent. J Med Chem 1992;35:3081-3084.
187. Bray GA, Gray DS: Treatment of obesity: an overview. Diab Metab Rev 1988;4:853-879.
188. Scopinaro N, Gianetta E, Civalleri D, Bonalumi U, Bachi V: Two years of clinical experience with bilio-pancreatic bypass for obesity. Am J Clin Nutr 1980;33:506-514.
189. Hadvary P, Lengsfeld H, Wolfer, H: Inhibition of pancreatic lipase in vitro by the covalent inhibitor tetrahydrolipstatin. J Biochem 1988;256:357-361.
190. Drent ML, Van der Veen EA: Lipase inhibition: a novel concept in the treatment of obesity. Int J Obes 1993;17:241-244.
191. Drent ML, Larsson I, William-Olsson T, Quaade F, Czubayko F, von Bergmann K, et al: Orlistat (RO 18-0647), a lipase inhibitor, in the treatment of human obesity: a multiple dose study. Int J Obes 1995;19:221-226.
192. Tonstad S, Pometta D, Erkelens DW, Ose L, Moccetti T, Schouten JA, et al: The effect of the gastrointestinal lipase inhibitor, orlistat, on serum lipids and lipoproteins in patients with primary hyperlipidaemia. Eur J Clin Pharmacol 1994;46:405-410.
193. Buckett WR, Luscombe GP, Thomas PC: BTS-54 254 - an approach to a rapidly acting antidepressant. In, Briley M, Fillion G (eds.): New Concepts in Depression. London: MacMillan, 1987;167-172.
194. Kelly F, Jones SP, Lee IK: Sibutramine: weight loss in depressed patients (abstract). Int J Obes 1995;19(suppl 2):145.
195. Connoley JP, Heal DJ: The thermogenic effects of sibutramine (abstract 52). Proceedings of Pharmacologic Treatment of Obesity, Satellite Symposium of the Seventh International Congress on Obesity, Saint Adele, Quebec, 1994.
196. Fantino M, Martel P: Decrease of food intake and weight loss induced by sibutramine in the rat (abstract 41). Proceedings of Pharmacologic Treatment of Obesity, Satellite Symposium of the Seventh International Congress on Obesity, Saint Adele, Quebec, 1994.
197. Stricker Krongrad A, Burlet C: Sibutramine effects on feeding behavior: a dose dependence and micro structural analysis (abstract 53). Proceedings of Pharmacologic Treatment of Obesity, Satellite Symposium of the Seventh International Congress on Obesity, Saint Adele, Quebec, 1994.
198. Weintraub M, Rubio A, Golik A, Byrne L, Scheinbaum ML: Sibutramine in weight control: a dose-ranging, efficacy study. Clin Pharmacol Ther 1991;50:330-337.
199. Bray GA, Ryan DH, Gordon D, Heidingsfelder S, Cerise F, Wilson K: A double-blind, randomized, placebo-controlled trial of sibutramine. Obes Res 1996;4:263-270.
200. Drouin P, Hanotin C, Courcier S, Leutenegger E: A dose ranging study: efficacy and tolerability of sibutramine in weight loss (abstract). Int J Obes 1994;18(suppl 2):60.
201. Jones SP, Newman BM, Romanec FM: Sibutramine hydrochloride: weight loss in overweight patients [abstract]. Int J Obes 1994;18(suppl 2):61.
202. Ryan DH, Kaiser P, Bray GA: Sibutramine: a novel new agent for obesity treatment. Obes Res 1995;3(suppl 4):553S-559S.
203. Kelly F, Wade AG, Jones SP, Johnson SG: Sibutramine hydrochloride vs. dexfenfluramine: weight loss in obese subjects (abstract). Int J Obes 1994;18(suppl 2):61.
204. Drouin P, Hanotin C, Thomas F, Leutenegger E: Efficacy and tolerability of sibutramine versus dexfenfluramine in obese patients [abstract]. Int J Obes 1995;19(suppl 2):144.
205. Vargas R, McMahon FG, Jain AK: Effects of sibutramine vs. placebo in NIDDM (abstract). Clin Pharmacol Ther 1995;54:188.
206. Griffiths J, Brynes AE, Frost G, Bloom SR, Finer N, Jones SP, Romanec FM: Sibutramine in the treatment of overweight non-insulin dependent diabetics (abstract). Int J Obes 1995;19(suppl 2):41.
207. King, DJ, Devaney N: Clinical pharmacology of sibutramine hydrochloride (BTS 54 524), a now antidepressant, in healthy volunteers. Br J Pharmacol 1988;26:607-611.
208. Wynne RD, Thornton GM, Slater NA, Lyons MB, Buckett WR: The effect of BTS 54 524, a novel antidepressant, on monamine reuptake and cardiovascular parameters in man (abstract). Acta Pharmacol Toxicol 1986;suppl 5:213.
209. Wynne RD, Brown T, Braybrooke RM, Jones S, Stott DA, Thornton GM: An evaluation of the cardiovascular effects of sibutramine in normal volunteers (abstract). Int J Obes 1995;19(suppl 2):144.
210. Kennedy GC: The hypothalamic control of food intake in rats. Proc R Soc London B 1950;137:535-549.
211. Rohner-Jeanrenaud F: A neuroendocrine reappraisal of the dual-centre hypothesis: its implications for obesity and insulin resistance. Int J Obes 1995;19:517-534.
212. Masuzaki H, Ogawa Y, Isse N: Human obese gene expression: adipocyte-specific expression and regional differences in the adipose tissue. Diabetes 1995;44:855-858.
213. Lonnqvist F, Arner P, Nordfors L, Schalling M: Overexpression of the obese (ob) gene in adipose tissue of human obese subjects. Nat Med 1995;1:950-953.
214. Hamilton BS, Paglia D, Kwan AYM, Deitel M: Increased obese mRNA expression in omental fat cells from massively obese humans. Nat Med 1995;1:953-956.
215. Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, et al: Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 1996;334:292-295.
216. Tartaglia LA, Dembski M, Weng X, Deng N, Culpepper J, Devos R, et al: Identification and expression cloning of a leptin receptor, OB-R. Cell 1995;83:1263-1271.
217. Stephens TW, Basinski M, Bristow PK, Bue-Valleskey JM, Burgett SG, Craft L, et al: The role of neuropeptide Y in the anti-obesity action of the obese gene product. Nature 1995;377:530-532.
218. Munglani R, Hudspith MJ, Hunt SP: The therapeutic potential of neuropeptide Y. Drugs 1996;52:371-389.
219. Grundemar L, Hakanson R: Neuropeptide Y effector systems: perspectives for drug development. Trends Pharmacol Sci 1994;15:153-159.
220. Wahlestedt C, Reis DJ: Neuropeptide Y-related peptides and their receptors - are the receptors potential therapeutic drug targets? Annu Rev Pharmacol Toxicol 1993;32:309-352.
221. Shine J, Potter EK, Biden T: Neuropeptide Y and regulation of the cardiovascular system. J Hypertens 1994;12(suppl):S41-S45.
222. Michel MC, Rascher W: Neuropeptide Y: a possible role in hypertension? J Hypertens 1995;13:385-395.
223. Erlanson-Albertsson C, Larsson A: The activation peptide of pancreatic procolipaso decreases food intake in rats. Regul Pept 1988;22:325-331.
224. Shargill NS, Tsujii S, Bray GA, Erlanson-Albertsson C: Enterostatin suppresses food intake following injection into the third ventricle of rats. Brain Res 1991;544:137-140.
225. Erlanson-Albertsson C, Mei J, Okada S, York D, Bray GA: Pancreatic procolipase propeptide-enterostatin specifically inhibits fat intake: Physiol Behav 1991;49:1191-1194.
226. Okada S, York DA, Bray GA, Erlanson-Albertsson C: Enterostatin, the activation peptide of procolipase, selectively reduces fat intake. Physiol Behav 1991;49:1185-1189.
227. Mei J, Cheng Y, Erlanson-Albertsson C: Enterostatin - its ability to inhibit insulin secretion and to decrease high-fat food intake. Int J Obes 1993;17:701-704.
228. Blundell JE, Halford JCG: Pharmacological aspects of obesity treatment: towards the 21st century. Int J Obes 1995;19(suppl 3):S51-S55.
229. Smith GP: Humoral mechanisms in the control of eating and body weight. In, Weiner H, Baum A (eds.): Perspectives in Behavioral Medicine, Eating Regulation and Discontrol. Hillsdale, NJ: Lawrence Erlbaum Associates, 1988;59-65.
230. Smith GP, Greenberg D, Corp E, Gibbs J: Afferent information in the control of eating. In, Bray GA, Ricquier D, Spiegelman BM (eds.): Obesity: Toward a Molecular Approach. New York: Wiley-Liss, 1990;63-79.
231. Smith GP, Jermoe C, Cushin BJ, Eterno R, Simansky KJ: Abdominal vagotomy blocks the satiety effect of cholecystokinin in the rat. Science 1981;213:1036-1037.
232. West DB, Fey D, Woods SC: Cholecystokinin persistently suppresses meal size but not food intake in free-feeding rats. Am J Physiol 1984;246:R776-R787.
233. McLaughlin CL, Peikin SR, Baile CA: Food intake response to modulation of secretion of cholecystokinin in Zucker rats. Am J Physiol 1983;244:R676-R685.
234. Mineka S, Snowdon CT: Inconsistency and possible habituation of CCK-induced satiety. Physiol Behav 1987;21:65-72.
235. Crawley JN, Beinfeld MC: Rapid development of tolerance to the behavioral actions of cholecystokinin. Nature 1987;302:703-706.
236. Kissilef HR, Pi-Sunyer X, Thornton J, Smith GP: C-terminal octapeptide of cholecystokinin decreases food intake in man. Am J Clin Nutr 1981;34:154-160.
237. Lieverse RJ, Jansen JBMJ, Zwan AV, Samson L, Masclee AAM, Lamers CBHW: Effects of a physiological dose of cholecystokinin on food intake and postprandial satiation in man. Regul Pept 1993;43:83-89.
238. Lieverse RJ, Jansen JBMJ, Masclee AAM, Lamers CBHW: Satiety effects of cholecystokinin in humans. Gastroenterology 1994;106:1451-1454.
239. Rose C, Vargas F, Facchinetti P, Bourgeat P, Bambal RB, Bishop PB, et al: Characterization and inhibition of a cholecystokinin-inactivating serine protease. Nature 1996;380:403-409.
240. Stuckey JA, Gibbs J, Smith GP: Neural disconnection of gut from brain blocks bombesin-induced satiety. Peptides 1985;6:1249-1252.
241. Gibbs J, Fauser DJ: Bombesin suppresses feeding in rats. Nature 1979;282:208-210.
242. Muurahainen NE, Kissileff HR, Pi-Sunyer FX: Intravenous infusion of bombesin reduces food intake in humans. Am J Physiol 1993;264:R350-R354.
243. Lieverse RJ, Jansen JBMJ, Masclee AAM, Lamers CBHW: Bombesin reduces food intake after a preload in man by a cholecystokinin-independent mechanism. Clin Sci 1993;85:277-280.
244. Lieverse RJ, Jansen JBMJ, Masclee AAM, Lamers CBHW: Significant satiety effect of bombesin in lean but not in obese subjects. Int J Obes 1994;18:579-583.
245. Edwards BJ, Morley JE: Amylin. Life Sci 1992;51:1899-1912.
246. Chance WT, Balasubramaniam A, Zhang FS, Wimalawansa SJ, Fischer JE: Anorexia following intrahypothalamic administration of amylin. Brain Res 1991;539:352-354.
247. Morley JE, Flood JF: The effect of amylin on food intake in normal and diabetic mice. Peptides 1991;12:865-870.
248. Morley JE, Flood JF, Horowitz M, Morley PMK, Walter MJ: Modulation of food intake by peripherally administered amylin. Am J Physiol 1994;267:R178-R184.
249. Cooper GJS: Amylin compared with calcitonin gene-related peptide: structure, biology, and relevance to metabolic disease. Endocr Rev 1994;15:163-201.
250. Cooper GJS: A reappraisal of current hypotheses concerning the possible roles of amylin in physiology, pathology and therapeutics. Clin Sci 1995;88:7-12.
251. Stridsberg M, Berne C, Sandler S, Wilander E, Oberg K: Inhibition of insulin secretion, but normal peripheral insulin sensitivity, in a patient with a malignanat endocrine apncreatic tumour prodcuing high amounts of an islet amyloid polypeptide-like molecule. Diabetologica 1993;36:843-849.
252. Young AA, Wang MW, Cooper GJS: Amylin injection causes elevated plasma lactate and glucose in the rat. FEBS Lett 1991; 291:101-104.
253. Gardiner SM, Compton AM, Kemp PA: Antagonistic effects of human alpha-calcitonin gene-related peptide (8-37) on regional hemodynamic actions of rat islet amyloid polypeptide in conscious Long-Evans rats. Diabetes 1991;40:948-951.
254. Behan DP, De Souza EB, Lowry PJ, Potter E, Sawchenko P, Vale WW: Corticotropin releasing factor (CRF) binding protein: a novel regulator of CRF and related peptides. Front Neuroendocrinol 1995;16:362-382.
255. Turton MD, O'Shea D, Gunn I, Beak SA, Edwards CMB, Meeran K, et al: A role for glucagon-like-peptide-1 in the central regulation of feeding. Nature 1996;379:69-72.
256. Ookuma J, Sakata T, Fukagawa K, Yoshimatsu H, Kurokawa M, Machidori H, Fujimoto K: Neuronal histamine in the hypothalmus suppresses food intake in rats. Brain Res 1993;628:235-242.
257. Shashoua VE, Hesse GW: N-docosahexaenoyl, 3 hydroxytyramine: a dopaminergic compound that penetrates the blood-brain barrier and suppresses appetite. Life Sci 1996;58:1347-1357.
258. National Task Force on the Prevention and Treatment of Obesity: Long-term pharmacotherapy in the management of obesity. JAMA 1996;276:1907-1915.
259. Gura T: Obesity sheds its secrets. Science 1997;275:751-754.