Drug dosage in the elderly: Dermatological drugs

Drugs and Aging

Volumn 23, Issue 3, 2006, Pages 203-215

  Flammiger, Anna ^a   Maibach, Howard ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLSALICYLIC ACID; ALEFACEPT; ANTICOAGULANT AGENT; ANTIHISTAMINIC AGENT; ANTIINFECTIVE AGENT; BENZODIAZEPINE; CALCIUM CHANNEL BLOCKING AGENT; CETIRIZINE; CIPROFLOXACIN; CORTICOSTEROID; CYCLOSPORIN; DERMATOLOGICAL AGENT; DESLORATADINE; DIAZEPAM; DIPHENHYDRAMINE; EFALIZUMAB; ENOXACIN; ETANERCEPT; ETRETIN; FLUCONAZOLE; IMMUNOLOGIC AGENT; ISONIAZID; ITRACONAZOLE; MACROLIDE; METHOTREXATE; NONSTEROID ANTIINFLAMMATORY AGENT; QUINOLINE DERIVED ANTIINFECTIVE AGENT; THEOPHYLLINE; TSUKUBAENOLIDE; UNINDEXED DRUG;

ACCIDENTAL INJURY; ACHILLES TENDON RUPTURE; AGING; AMNESIA; ATTENTION DEFICIT DISORDER; BEHAVIOR DISORDER; BIOTRANSFORMATION; BODY COMPOSITION; CHOLESTASIS; COGNITIVE DEFECT; COMMON COLD; CONSCIOUSNESS DISORDER; CUSHINGOID SYNDROME; DEMOGRAPHY; DIABETES MELLITUS; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG DISTRIBUTION; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG INDUCED HEADACHE; DRUG METABOLISM; DRUG SAFETY; DRUG TOLERABILITY; HEPATITIS; HUMAN; INFECTION; INJECTION SITE REACTION; LIVER; LIVER FAILURE; LIVER FIBROSIS; LIVER INJURY; LIVER TOXICITY; LOW DRUG DOSE; MEMORY DISORDER; NONHUMAN; PEPTIC ULCER; PHARYNGITIS; PRESCRIPTION; PRIORITY JOURNAL; PSORIASIS; PSYCHOMOTOR DISORDER; RESPIRATORY TRACT DISEASE; REVIEW; RHEUMATOID ARTHRITIS; SEDATION; SEIZURE; SIDE EFFECT; SKIN CARCINOMA; SLEEP DISORDER; SLEEP WAKING CYCLE;

AGED; AGED, 80 AND OVER; AGING; ANTI-INFECTIVE AGENTS; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; BIOLOGICAL AVAILABILITY; DERMATOLOGIC AGENTS; DRUG INTERACTIONS; HUMANS; PHARMACEUTICAL PREPARATIONS; PHARMACOKINETICS;

EID: 33645763956     PISSN: 1170229X     EISSN: 1170229X     Source Type: Journal    
DOI: 10.2165/00002512-200623030-00003     Document Type: Review

References (120)

1. Kinsella K, Velkoff VA. U.S. Census Bureau, Series P95/01-1, an aging world: 2001, US Government Printing Office, Washington, DC, 2001 [online]. Available from URL: http://www.census.gov [Accessed 2005 Sep 6]
2. United Nations Expert Group Meeting on Social and Economic Implications of Changing Population Age Structure, Population Division, Department of Economic and Social Affairs, United Nations Secretariat, Mexico City, 31 Aug-2 Sept 2005 [online]. Available from URL: http://www.unpopulation.org [Accessed 2005 Sep 6]
3. Beauregard S, Gilchrest BA. A survey of skin problems and skin care regimens in the elderly. Arch Dermatol 1987; 123: 1638-43
4. Hurwitz N. Predisposing factors in adverse reactions to drugs. BMJ 1969; 1: 536-9
5. Klein U, Klein M, Sturm H, et al. The frequency of adverse drug reactions as dependent upon age, sex and duration of hospitalization. Int J Clin Pharmacol 1976; 13 (3): 187-95
6. Rheumatoid Arthritis Clinical Trial Archive Group. The effect of age and renal function on the efficacy and toxicity of methotrexate in rheumatoid arthritis. J Rheumatol 1999; 22 (2): 218-23
7. Smith ES, Fleischer AB, Feldman SR. Demographics of aging and skin disease. Clin Geriatr Med 2001; 17 (4): 631-41
8. Gurwitz JH, Avorn J. The ambiguous relation between aging and adverse drug reactions. Ann Intern Med 1991; 114: 956-66
9. Begaud B, Martin K, Fourrier A, et al. Does age increase the risk of adverse drug reactions? J Clin Pharmacol 2002; 54: 550-2
10. Mannesse CK, Derkx FHM, De Ridder MA, et al. Contribution of adverse drug reactions to hospital admission of older patients. Age Ageing 2000; 29: 35-9
11. Onder G, Pedone C, Landi F, et al. Adverse drug reactions as cause of hospital admissions: results from the Italian Group of Pharmacoepidemiology in the Elderly (GIFA). J Am Geriatr Soc 2002; 50: 1962-8
12. Lassila HC, Stoehr GP, Ganguli M, et al. Use of prescription medications in an elderly rural population: the MoVIES Project. Ann Pharmacother 1996; 30: 589-95
13. Pilotto A, Franceschi M, Leandro M, et al. NSAID and aspirin use by the elderly in general practice. Drugs Aging 2003; 20: 701-10
14. Caamano F, Pedone C, Zuccala G, et al. Socio-demographic factors related to the prevalence of adverse drug reactions at hospital admission in an elderly population. Arch Gerontol Geriatr 2005; 40: 45-52
15. Eriksen HM, Iversen BG, Aavitsland P. Prevalence of nosocomial infections and use of antibiotics in long-term care facilities in Norway, 2002 and 2003. J Hosp Infect 2004; 57: 316-20
16. Laube S. Skin infections and ageing. Ageing Res Rev 2004; 3 (1): 69-89
17. Laube S, Farrell AM. Bacterial infections in the elderly: diagnosis and treatment. Drugs Aging 2002; 19 (5): 331-42
18. Leistevuo T, Isoaho R, Klaukka T, et al. Prescription of antimicrobial agents to elderly people in relation to the type of infection. Age Ageing 1997; 26 (5): 345-51
19. Engelhart ST, Hanses-Derendorf L, Exner M, et al. Prospective surveillance for healthcare-associated infections in German nursing home residents. J Hosp Infect 2005; 60 (1): 46-50
20. Gregg CR. Drug interactions and anti-infective therapies. Am J Med 1999; 106: 227-37
21. Pea F, Furlanut M. Pharmacokinetic aspects of treating infections in the intensive care unit: focus on drug interactions. Clin Pharmacokinet 2001; 40 (11): 833-68
22. Singer MI, Shapiro LE, Shear NH. Cytochrome P-450 3: interactions with dermatologic therapies. J Am Acad Dermatol 1997; 37: 765-71
23. Keenan PA, Jacobson MW, Soleymani RM, et al. The effect of memory of chronic prednisone treatment in patients with systemic disease. Neurology 1996; 47 (6): 1396-402
24. Blackburn D, Hux J, Mamdani M. Quantification of the risk of corticosteroid-induced diabetes mellitus among the elderly. J Gen Intern Med 2002; 17: 717-20
25. Piper JM, Ray WA, Daugherty JR, et al. Corticosteroid use and peptic ulcer disease: role of nonsteroidal anti-inflammatory drugs. Ann Intern Med 1991; 114: 735-40
26. Agostini JV, Leo-Summers LS, Inouye SK. Cognitive and other adverse effects of diphenhydramine use in hospitalized older patients. Arch Intern Med 2001; 161: 2091-7
27. Simons KJ, Watson WTA, Chen XY, et al. Pharmacokinetic and pharmacodynamic studies of the H1-receptor antagonist hydroxyzine in the elderly. Clin Pharmacol Ther 1989; 45 (1): 9-14
28. Kaliner MA. H1-antihistamines in the elderly. Clin Allergy Immunol 2002; 17: 465-81
29. Matzke GR, Yeh J, Awni WM, et al. Pharmacokinetics of cetirizine in the elderly and patients with renal insufficiency. Ann Allergy 1987; 59: 25-30
30. Tarzi R, Palmer A. Treatment in patients with renal disease. In: Wakelin SH, Maibach HI, editors. Handbook of systemic drug treatment in dermatology. London: Manson, 2004: 263-71
31. Whiting-O'Keefe QE, Fye KH, Sack KD. Methotrexate and histological hepatic abnormalities: a meta-analysis. Am J Med 1991; 90: 771-6
32. Robles W. Antifungals. In: Wakelin SH, Maibach HI, editors. Handbook of systemic drug treatment in dermatology. London: Manson, 2004: 44-70
33. Teare J, Puleston J. Treatment in patients with liver disease. In: Wakelin SH, Maibach HI, editors. Handbook of systemic drug treatment in dermatology. London: Manson, 2004: 272-9
34. Nilsson-Ehle I, Ljungberg B. Quinolone disposition in the elderly: practical implications. Drugs Aging 1991; 1 (4): 279-88
35. Van der Linden PD, Sturkenboom MC, Herings RM, et al. Increased risk of achilles tendon rupture with quinolone antibacterial use, especially in elderly patients taking oral corticosteroids. Arch Intern Med 2003; 163 (15): 1801-7
36. Gebhard KL, Maibach HI. Relationship between systemic corticosteroids and osteonecrosis. Am J Clin Dermatol 2001; 2 (6): 377-88
37. Saag KG, Furst DE. Major side effects of glucocorticoids: Up To Date. 2006 [online]. Available from URL: http://www.utdol.com [Accessed 2006 Jan 22]
38. Routledge PA, O'Mahony MS, Woodhouse KW. Adverse drug reactions in elderly patients. Br J Clin Pharmacol 2003; 57 (2): 121-6
39. Griffin MR, Piper JM, Daugherty JR, et al. Nonsteroidal antiinflammatory drug use and increased risk for peptic ulcer disease in elderly persons. Ann Intern Med 1991; 114: 257-63
40. Mann RD, Pearce GL, Dunn N, et al. Sedation with 'non-sedating' antihistamines: four prescription-event monitoring studies in general practice. BMJ 2000; 320: 1184-7
41. Affrime M, Gupta S, Banfield C, et al. A pharmacokinetic profile of desloratadine in healthy adults, including elderly. Clin Pharmacokinet 2002; 41 (1 Suppl.): 13-9
42. Gottlieb AB. Therapeutic options in the treatment of psoriasis and atopic dermatitis. J Am Acad Dermatol 2005; 53: S3-16
43. Yosipovitch G, Tang MBY. Practical management of psoriasis in the elderly: epidemiology, clinical aspects, quality of life, patient education and treatment options. Drugs Aging 2002; 19 (11): 847-63
44. Scheinfeld N. Alefacept: a safety profile. Expert Opin Drug Saf 2005; 4 (6): 975-85
45. Gottlieb AB, Boehncke WH, Darif M. Safety and efficacy of alefacept in elderly patients and other special populations. J Drugs Dermatol 2005; 4 (6): 718-24
46. Joshi A, Bauer R, Kuebler P, et al. An overview of the pharmacokinetics and pharmacodynamics of efalizumab: a monoclonal antibody approved for use in psoriasis. J Clin Pharmacol 2006; 46 (1): 10-20
47. Gottlieb A, Lizzul P. Safety and efficacy of efalizumab therapy for elderly patients with moderate to severe chronic plaque psoriasis [poster]. J Am Acad Dermatol 2005; 52 Suppl. 3: P194
48. Bissonette R. Etanercept for the treatment of psoriasis. Skin Therapy Lett 2006; 11 (1): 1-4
49. Gottlieb AB, Leonardi CL, Goffe BS, et al. Etanercept monotherapy in patients with psoriasis: a summary of safety, based on an integrated multistudy database. J Am Acad Dermatol 2006; 54 (3 Suppl. 2): S92-100
50. Bathon JM, Fleischmann RM, van der Heijde D, et al. Safety and efficacy of etanercept treatment in elderly subjects with rheumatoid arthritis. J Rheumatol 2006; 33 (2): 234-43
51. Fleischmann RM, Baumgartner SW, Tindall EA, et al. Response to etanercept (Enbrel) in elderly patients with rheumatoid arthritis: a retrospective analysis of clinical trial results. J Rheumatol 2003; 30 (4): 691-6.
52. Forbes GB, Reina JC. Adult lean body mass declines with age: some longitudinal observations. Metabolism 1970; 19 (9): 653-62
53. Novak LP. Aging, total body potassium, fat-free mass, and cell mass in males and females between ages 18 and 85 years. J Gerontol 1972; 27 (4): 438-43
54. Choudhury D, Ray DSC, Levi M. Effect of aging on renal function and disease. In: Brenner BM, editor. Brenner and Rector's, The kidney. Elsevier, 2004: 2305-42
55. Rowe JW, Andres R, Tobin JD, et al. The effect of age on creatinine clearance in men: a cross-sectional and longitudinal study. J Gerontol 1976; 31 (2): 155-63
56. Woodhouse KW, James OFW. Hepatic drug metabolism and ageing. Br Med Bull 1990; 46 (10): 22-35
57. Wynne HA, Goudevenos J, Rawlins MD, et al. Hepatic clearance: the effect of age using indocyanine green as a model compound. Br J Clin Pharmacol 1990; 30: 634-7
58. Roskos KV, Maibach HI, Guy RH. The effect of aging on percutaneous absorption in man. J Pharmacokinet Biopharm 1989; 17 (6): 617-30
59. Iber FL, Murphy PA, Connor ES. Age-related changes in the gastrointestinal system: effects on drug therapy. Drugs Aging 1994; 5: 34-48
60. Tumer N, Scarpace PJ, Lownthal DT. Geriatric pharmacology: basic and clinical considerations. Annu Rev Pharmacol Toxicol 1992; 32: 271-302
61. Roskos KV, Maibach HI. Percutaneous absorption and age. Implications for therapy. Drugs Aging 1992; 2 (5): 432-49
62. Vestal RE, Gurwitz JH. Geriatric pharmacology. In: Carruthers SG, Hoffman BB, Melmon KL, et al., editors. Melmon and Morrelli's Clinical Pharmacology. New York: McGraw Hill, 2000: 1151-77
63. Turnheim K. When drug therapy gets old: pharmacokinetics and pharmacodynamics in the elderly. Exp Gerontol 2003; 38: 843-53
64. Vestal RE, McGuire EA, Tobin JD, et al. Aging and ethanol metabolism. Clin Pharmacol Ther 1976; 21 (3): 343-54
65. Shah RR. Drug development and use in the elderly: search for the right dose and dosing regimen. Br J Clin Pharmacol 2004; 58 (5): 452-69
66. Klotz U, Avant GR, Hoyumpa A, et al. The effects of age and liver disease on the disposition and elimination of diazepam in adult man. J Clin Invest 1975; 55: 347-59
67. Turnheim K. Drug dosage in the elderly. Is it rational? Drugs Aging 1998; 13 (5): 357-79
68. Campion EW, Avorn J, Reder VA, et al. Overmedication of the low-weight elderly. Arch Intern Med 1987; 147: 945-7
69. Hanlon JT, Ruby CM, Shelton PS, et al. Geriatrics. In: DiPiro JT, Talbert RL, Yee GC, et al., editors. Pharmacotherapy: a pathophysiologic approach. New York: McGraw Hill, 1999: 52-61
70. Greenblatt DJ. Reduced serum albumin concentration in the elderly: a report from the Boston Collaborative Drug Surveillance Program. J Am Geriatr Soc 1979; 27: 20-2
71. Abernethy DR, Kerzner L. Age effects on alpha-1-acid glycoprotein concentration and imipramine plasma protein binding. J Am Geriatr Soc 1984; 32: 705-8
72. Katzung BG. Special aspects of geriatric pharmacology. In: Katzung BG, editor. Basic and clinical pharmacology. New York: McGraw Hill, 2004: 1007-14
73. Wallace SM, Verbeeck RK. Plasma protein binding of drugs in the elderly. Clin Pharmacokinet 1987; 12: 41-72
74. Lindeman RD, Tobin J, Shock NW. Longitudinal studies on the rate of decline in renal function with age. J Am Geriatr Soc 1985; 33: 278-85
75. Papaioannou A, Clarke JA, Campbell G, et al. Clinical investigation: assessment of adherence to renal dosing guidelines in long term care facilities. J Am Geriatr Soc 2000; 48 (11): 1470-3
76. Cantu TG, Ellerbeck EF, Yun SW, et al. Drug prescribing for patients with changing renal function. Am J Hosp Pharm 1992; 49: 2944-8
77. Henderson ES, Adamson RH, Oliviero VT. The metabolic fate of tritiated methotrexate. II: absorption and excretion in man. Cancer Res 1965; 25: 1018-24
78. Kristensen O, Weisman K, Hutters L. Renal function and the rate of disappearance of methotrexate from serum. Eur J Clin Pharmacol 1975; 8: 439-44
79. Bressolle F, Bologna C, Kinowski JM, et al. Effect of moderate renal insufficiency on pharmacokinetics of methotrexate in rheumatoid arthritis patients. Ann Rheum Dis 1998; 57: 110-3
80. Kremer JM, Hamilton RA. The effects of nonsteroidal antiinflammatory drugs on methotrexate (MTX) pharmacokinetics: impairment of renal clearance of MTX at weekly maintenance doses but not at 7.5 mg. J Rheumatol 1995; 22: 2072-7
81. Yosipovitch G, Tang MBY. Practical management of psoriasis in the elderly. Epidemiology, clinical aspects, quality of life, patient education and treatment options. Drugs Aging 2002; 19 (11): 847-63
82. Karim A, Tolbert DS, Hunt TL, et al. Celecoxib, a specific COX-2 inhibitor, has no significant effect on methotrexate pharmacokinetics in patients with rheumatoid arthritis. J Rheumatol 1999; 26 (12): 2539-43
83. Fairris GM, Dewhurst AG, White JE, et al. Methotrexate dosage in patients aged over 50 with psoriasis. BMJ 1989; 298: 801-2
84. Simons FER, Simons KJ. The pharmacology and use of H1-receptor-antagonist drugs. N Engl J Med 1994; 330 (23): 1663-70
85. Robbins DK, Horton MW, Swan SK, et al. Pharmacokinetics of fexofenadine in patients with varying degrees of renal impairment [abstract]. Pharmaceutical Res 1996; 13 Suppl. 9: S431
86. Shannon JA. The renal excretion of creatinine in man. J Clin Invest 1935; 14: 403-10
87. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16: 31-41
88. Goldberg TH, Finkelstein MS. Difficulties in estimating glomerular filtration rate in the elderly. Arch Intern Med 1987; 147: 1430-3
89. Dreisbach AW, Lertora JJL. The effect of chronic renal failure on hepatic drug metabolism and drug disposition. Semin Dial 2003; 16 (1): 45-50
90. Guevin C, Michaud J, Naud J, et al. Down-regulation of hepatic cytochrome P450 in chronic renal failure: role of uremic mediators. Br J Pharmacol 2002; 137: 1039-46
91. Taburet AM, Vincent I, Perello L. Impairment of drug biotransformation in renal disease: An in vitro model [abstract]. Am Soc Clin Pharmacol Ther 1996; 59: 136
92. Schmucker DL. Liver function and phase I drug metabolism in the elderly. Drugs Aging 2001; 18 (11): 837-51
93. Le Couteur DG, McLean AJ. The aging liver: drug clearance and an oxygen diffusion barrier hypothesis. Clin Pharmacokinet 1998; 34 (5): 359-73
94. Correia MA. Drug biotransformation. In: Katzung BG, editor. Basic and clinical pharmacology. New York: McGraw Hill, 2004: 51-63
95. Sotaniemi EA, Arranto AJ, Pelkonen O, et al. Age and cytochrome P450-linked drug metabolism in humans: an analysis of 226 subjects with equal histopathologic conditions. Clin Pharmacol Ther 1997; 61: 331-9
96. Miners JO, Penhall R, Robson RA. Comparison of paracetamol metabolism in young adult and elderly males. Eur J Clin Pharmacol 1988; 35: 157-60
97. Schmucker DL, Woodhouse KW, Wang RK, et al. Effects of age and gender on in vitro properties of human liver microsomal monooxygenases. Clin Pharmacol Ther 1990; 48: 365-74
98. Wynne H, Mutch E, James OFW, et al. The effect of age upon the affinity of microsomal monooxygenase enzymes for substrate in human liver. Age Ageing 1988; 17: 401-5
99. Hunt CM, Westerkam WR, Stave GM. Effect of age and gender on the activity of human hepatic CYP3A. Biochem Pharmacol 1992; 44 (2): 275-83
100. Sanz N, Diez-Fernandez C, Alvarez AM, et al. Age-related changes on parameters of experimentally-induced liver injury and regeneration. Toxicol Appl Pharmacol 1999; 154: 40-9
101. Schmucker DL. Age-related changes in liver structure and function: implications for disease? Exp Gerontol 2005; 40 (8-9): 650-9
102. Regev A, Schiff ER. Liver disease in the elderly. Gastroenterol Clin North Am 2001; 30 (2): 547-62
103. Almdal TP, Sorensen TIA. The Danish Association for the Study of the Liver: incidence of parenchymal liver diseases in Denmark, 1981 to 1985. Analysis of hospitalization registry data. Hepatology 1991; 13 (4): 650-5
104. Kopanoff DE, Snider DE, Caras GJ. Isoniazid: related hepatitis. Am Rev Resp Dis 1978; 117: 991-1001
105. Walker AM, Funch D, Dreyer NA, et al. Determinants of serious liver disease among patients receiving low-dose methotrexate for rheumatoid arthritis. Arthritis Rheum 1993; 36 (3): 329-35
106. Roenigk HH, Auerbach R, Maibach H, et al. Methotrexate in psoriasis: consensus conference. J Am Acad Dermatol 1998; 38 (3): 478-85
107. Rodriguez LA, Duque A, Castellsague J, et al. A cohort study on the risk of acute liver injury among users of ketoconazole and other antifungal drugs. Br J Clin Pharmacol 1999; 48: 847-52
108. Adriaenssens B, Roskams T, Steger P, et al. Hepatotoxicity related to itraconazole: report of three cases. Acta Clin Belg 2001; 56 (6): 364-9
109. Gallardo-Quesada S, Luelmo-Aguilar J, Guanyabens-Calvet C, et al. Hepatotoxicity associated with itraconazole. Int J Dermatol 1995; 34 (8): 589
110. Lavrijsen APM, Balmus KJ, Nugteren-Huying WM, et al. Hepatic injury associated with itraconazole. Lancet 1992; 340: 251-2
111. FDA. FDA Talk Paper, May 2001. FDA issues health advisory regarding the safety of Sporanox® products and Lamisil® tablets to treat fungal nail infections [online]. Available from URL: http://www.fda.gov [Accessed 2005 Aug 25]
112. Kreiss C, Amin S, Nalesnik MA, et al. Severe cholestatic hepatitis in a patient taking acitretin. Am J Gastroenterol 2002; 97 (3): 775-7
113. Van Ditzhuijsen TJM, Van Haelst UJGM, Van Dooren-Grebe RJ, et al. Severe hepatotoxic reaction with progression to cirrhosis after use of a novel retinoid (acitretin). J Hepatol 1990; 11: 185-8
114. Roenigk HH, Callen JP, Guzzo CA, et al. Effects of acitretin on the liver. J Am Acad Dermatol 1999; 41: 584-8
115. Feely J, Coakley D. Altered pharmacodynamics in the elderly. Clin Pharmacol 1990; 6 (2): 269-83
116. Swift CG. Pharmacodynamics: changes in homeostatic mechanisms, receptor and target organ sensitivity in the elderly. Br Med Bull 1990; 46 (1): 36-52
117. Greenblatt DJ, Harmatz JS, Shader RI. Clinical pharmacokinetics of anxiolytics and hypnotics in the elderly. Therapeutic considerations (Part II). Clin Pharmacokinet 1991; 21 (4): 262-73
118. Fleischer AB. Pruritus in the elderly: management by senior dermatologists. J Am Acad Dermatol 1993; 28: 603-9
119. Col N, Fanale JE, Kronholm P. The role of medication noncompliance and adverse drug reactions in hospitalizations of the elderly. Arch Intern Med 1990; 150 (4): 841-5
120. Ruscin JM, Semla TP. Assessment of medication management skills in older outpatients. Ann Pharmacother 1996; 30 (10): 1083-8