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Influence of Cocaine, Ethanol, or Their Combination on Epicardial Coronary Arterial Dimensions in Humans

Influence of Cocaine, Ethanol, or Their Combination on Epicardial Coronary Arterial Dimensions in... Abstract Background: Cocaine and ethanol are often abused concomitantly, and this combination may be more lethal than either substance alone. Although previous studies showed that cocaine causes coronary arterial vasoconstriction, the combined effect of cocaine and ethanol on the coronary vasculature in humans is unknown. Thus, we assessed the effects of intranasal cocaine, intravenous ethanol, or a cocaine-ethanol combination on heart rate, systemic arterial pressure, and coronary arterial dimensions in humans. Methods: Thirty-four subjects with chest pain (27 men and seven women, aged 34 to 67 years) who were referred for catheterization received one of the following pharmacologic interventions: (1) intranasal (2 mL) and intravenous (5 mL/kg) saline (n=8 [group A]); (2) intranasal cocaine (2 mg/kg) and intravenous saline (5 mL/ kg) (n=9 [group B]); (3) intranasal saline (2 mL) and intravenous 10% ethanol (5 mL/kg) (n=9 [group C]); or (4) intranasal cocaine (2 mg/kg) and intravenous 10% ethanol (5 mL/kg) (n=8 [group D]). Heart rate, systemic arterial pressure, left coronary arterial dimensions (by computer-assisted quantitative angiography), as well as blood cocaine, ethanol, and cocaine metabolite concentrations were measured before and 30,60, and 90 minutes after initiation of the intravenous infusions. Results: No hemodynamic or angiographic changes were observed in the group A (saline) subjects. In the group B (cocaine) subjects, the heart rate—systolic arterial pressure product increased by 5% and 10% at 30 and 90 minutes, respectively, and coronary arterial diameter decreased by 14% at these times. In the group C (ethanol) subjects, no hemodynamic changes were noted, but coronary arterial diameters increased by 12%, 11%, and 12% at 30, 60, and 90 minutes, respectively. In the group D (cocaine-ethanol) patients, rate-pressure product increased by 17%, 10%, and 16%, and coronary arterial diameters increased by 7%, 12%, and 13%, at 30, 60, and 90 minutes, respectively. Conclusion: The combination of intranasal cocaine and intravenous ethanol causes an increase in the determinants of myocardial oxygen demand. However, it also causes a concomitant increase in epicardial coronary arterial diameter.(Arch Intern Med. 1995;155:1186-1191) References 1. Lange RA, Cigarroa RG, Yancy CW Jr, et al. Cocaine-induced coronary-artery vasoconstriction. N Engl J Med . 1989;321:1557-1562.Crossref 2. Flores ED, Lange RA, Cigarroa RG, Hillis LD. Effect of cocaine on coronary artery dimensions in atherosclerotic coronary artery disease: enhanced vasoconstriction at sites of significant stenoses. J Am Coll Cardiol . 1990;16:74-79.Crossref 3. Brogan WC III, Lange RA, Glamann DB, Hillis LD. Recurrent coronary vasoconstriction caused by intranasal cocaine: possible role for metabolites. Ann Intern Med . 1992;116:556-561.Crossref 4. Boehrer JD, Moliterno DJ, Willard JE, et al. Hemodynamic effects of intranasal cocaine in humans. J Am Coll Cardiol . 1992;20:90-93.Crossref 5. Isner JM, Estes NAM III, Thompson PD, et al. Acute cardiac events temporally related to cocaine abuse. N Engl J Med . 1986;315:1438-1443.Crossref 6. Smith HWB III, Liberman HA, Brody SL, Battey LL, Donohue BC, Morris DC. Acute myocardial infarction temporally related to cocaine use: clinical, angiographic, and pathophysiologic observations. Ann Intern Med . 1987;107:13-18.Crossref 7. Cregler LL, Mark H. Relation of acute myocardial infarction to cocaine abuse. Am J Cardiol . 1985;56:794.Crossref 8. Schachne JS, Roberts BH, Thompson PD. Coronary-artery spasm and myocardial infarction associated with cocaine use. N Engl J Med . 1984;310:1665-1666.Crossref 9. Rod JL, Zucker RP. Acute myocardial infarction shortly after cocaine inhalation. Am J Cardiol . 1987;59:161.Crossref 10. Weiss RJ. Recurrent myocardial infarction caused by cocaine abuse. Am Heart J . 1986;111:793.Crossref 11. Kossowsky WA, Lyon AF. Cocaine and acute myocardial infarction: a probable connection. Chest . 1984;86:729-731.Crossref 12. Zimmerman FH, Gustafson GM, Kemp HG Jr. Recurrent myocardial infarction associated with cocaine abuse in a young man with normal coronary arteries: evidence for coronary artery spasm culminating in thrombosis. J Am Coll Cardiol . 1987;9:964-968.Crossref 13. Hadjimiltiades S, Covalesky V, Manno BV, Haas WS, Mintz GS. Coronary arteriographic findings in cocaine abuse-induced myocardial infarction. Cathet Cardiovasc Diagn . 1988;14:33-36.Crossref 14. Nanji AA, Filipenko JD. Asystole and ventricular fibrillation associated with cocaine intoxication. Chest . 1984;85:132-133.Crossref 15. Karch SB, Billingham ME. The pathology and etiology of cocaine-induced heart disease. Arch Pathol Lab Med . 1988;112:225-230. 16. Benchimol A, Bartall H, Dresser KB. Accelerated ventricular rhythm and cocaine abuse. Ann Intern Med . 1978;88:519-520.Crossref 17. Young D, Glauber JJ. Electrocardiographic changes resulting from acute cocaine intoxication. Am Heart J . 1947;34:272-279.Crossref 18. Allred RJ, Ewer S. Fatal pulmonary edema following intravenous free-base cocaine use. Ann Emerg Med . 1981;10:441-442.Crossref 19. Wetli CV, Wright RK. Death caused by recreational cocaine use. JAMA . 1979; 214:2519-2522.Crossref 20. Bertolet BD, Freund G, Martin CA, Perchalski DL, Williams CM, Pepine CJ. Unrecognized left ventricular dysfunction in an apparently healthy cocaine abuse population. Clin Cardiol . 1990;13:323-328.Crossref 21. Chokshi SK, Moore R, Pandian NG, Isner JM. Reversible cardiomyopathy associated with cocaine intoxication. Ann Intern Med . 1989;111:1039-1040.Crossref 22. Grant BF, Harford TC. Concurrent and simultaneous use of alcohol with cocaine: results of a national survey. Drug Alcohol Depend . 1990;25:97-104.Crossref 23. National Institute on Drug Abuse, Drug Abuse Warning Network. Annual Medical Examiner Data—1990 . Washington, DC: Government Printing Office; 1991. US Dept of Health and Human Services publication No. (ADM) 91-1840. 24. National Institute on Drug Abuse. Data From the Drug Abuse Warning System (DAWN): Annual Data 1987 . Washington, DC: Government Printing Office; 1988. US Dept of Health and Human Services publication No. (ADM) 88-1584. 25. Rose S, Hearn WL, Hime GW, Wetli CV, Ruttenber AJ, Mash DC. Cocaine and cocaethylene concentrations in human postmortem cerebral cortex. Neuroscience . 1990:16:14. Abstract. 26. Escobedo LG, Ruttenber AJ, Agocs MM, Anda RF, Wetli CV. Emerging patterns of cocaine use and the epidemic of cocaine overdose deaths in Dade County, Florida. Arch Pathol Lab Med . 1991;115:900-905. 27. Altura BM, Altura BT, Carella A. Ethanol produces coronary vasospasm: evidence for a direct action of ethanol on vascular muscle. Br J Pharmacol . 1983; 78:260-262.Crossref 28. Hayes SN, Bove AA. Ethanol causes epicardial coronary artery vasoconstriction in the intact dog. Circulation . 1988;78:165-170.Crossref 29. Pescio S, Macho P, Penna M, Domenech RJ. Changes in total and transmural coronary blood flow induced by ethanol. Cardiovasc Res . 1983;17:604-607.Crossref 30. Abel FL. Direct effects of ethanol on myocardial performance and coronary resistance. J Pharmacol Exp Ther . 1980;212:28-33. 31. Ganz V. The acute effect of alcohol on the circulation and on the oxygen metabolism of the heart. Am Heart J . 1963;66:494-497.Crossref 32. Lasker N, Sherrod TR, Kilam KF. Alcohol on the coronary circulation of the dog. J Pharmacol Exp Ther . 1955;13:414-420. 33. Cigarroa RG, Lange RA, Popma JJ, et al. Ethanol-induced coronary vasodilation in patients with and without coronary artery disease. Am Heart J . 1990; 119:254-259.Crossref 34. Uszenski RT, Gillis RA, Schaer GL, Analouei AR, Kuhn FE. Additive myocardial depressant effects of cocaine and ethanol. Am Heart J . 1992;124:1276-1283.Crossref 35. Gobel FL, Nordstrom LA, Nelson RR, Jorgensen CR, Wang Y. The rate-pressure product as an index of myocardial oxygen consumption during exercise in patients with angina pectoris. Circulation . 1978;57:549-556.Crossref 36. Baller D, Bretschneider HJ, Hellige G. Validity of myocardial oxygen consumption parameters. Clin Cardiol . 1979;2:317-327.Crossref 37. Isenschmid D, Levine B, Caplan Y. A method for the simultaneous determination of cocaine, benzoylecgonine, and ecgonine methyl ester in blood and urine using GC/EIMS with derivatization to produce high mass molecular ions. J Anal Toxicol . 1988;12:242-245.Crossref 38. Reiber JHC, Serruys PW, Kooijman CJ, et al. Assessment of short-, medium-, and long-term variations in arterial dimensions from computer-assisted quantitation of coronary cineangiograms. Circulation . 1985;71:280-288.Crossref 39. Zar JH. Biostatistical Analysis . Englewood Cliffs, NJ: Prentice Hall International Inc; 1974:152-154. 40. Cregler LL, Mark H. Medical complications of cocaine abuse. N Engl J Med . 1986;315:1495-1500.Crossref 41. Jones RT. Psychopharmacology of cocaine. In: Washington AM, Gold MS, eds. Cocaine: A Clinician's Handbook . New York, NY: Guilford; 1987:55-72. 42. Hearn WL, Keran EE, Wei H, Hime G. Site-dependent postmortem changes in blood cocaine concentrations. J Forensic Sci . 1991;36:673-684. 43. Van Dyke C, Barash PG, Jatlow P. Cocaine: plasma concentrations after intranasal application in man. Science . 1976;191:859-861.Crossref 44. Van Dyke C, Jatlow P, Ungerer J, Barash PG, Byck R. Oral cocaine: plasma concentrations and central effects. Science . 1978;200:211-213.Crossref 45. Foltin RW, Fischman MW. Ethanol and cocaine interactions in humans: cardiovascular consequences. Pharmacol Biochem Behav . 1989;31:877-883.Crossref 46. Farre M, de la Torre R, Llorente M, et al. Alcohol and cocaine interactions in humans. J Pharmacol Exp Ther . 1992;260:939-946. 47. Hearn WL, Flynn DD, Hime GW, et al. Cocaethylene: a unique cocaine metabolite displays high affinity for the dopamine transporter. J Neurochem . 1991; 56:698-701.Crossref 48. Dean RA, Christian CD, Sample RHB, Bosron WF. Human liver cocaine esterases: ethanol-mediated formation of ethylcocaine. FASEB J . 1991;5:2735-2739. 49. Hime GW, Hearn WL, Rose S, Cofino J. Analysis of cocaine and cocaethylene in blood and tissues by GC-NPD and GC-ion trap mass spectrometry. J Anal Toxicol . 1991;15:241-245.Crossref 50. Hearn WL, Rose S, Wagner J, Ciarleglio A, Mash DC. Cocaethylene is more potent than cocaine in mediating lethality. Pharmacol Biochem Behav . 1991; 39:531-533.Crossref 51. Caughlin LJ, O'Halloran RL. An accidental death related to cocaine, cocaethylene, and caffeine. J Forensic Sci . 1993;38:1513-1515. 52. Perez-Reyes M, Jeffcoat R. Ethanol/cocaine interaction: cocaine and cocaethylene plasma concentrations and their relationship to subjective cardiovascular effects. Life Sci . 1992;51:553-563.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

Influence of Cocaine, Ethanol, or Their Combination on Epicardial Coronary Arterial Dimensions in Humans

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Publisher
American Medical Association
Copyright
Copyright © 1995 American Medical Association. All Rights Reserved.
ISSN
0003-9926
eISSN
1538-3679
DOI
10.1001/archinte.1995.00430110100011
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Abstract

Abstract Background: Cocaine and ethanol are often abused concomitantly, and this combination may be more lethal than either substance alone. Although previous studies showed that cocaine causes coronary arterial vasoconstriction, the combined effect of cocaine and ethanol on the coronary vasculature in humans is unknown. Thus, we assessed the effects of intranasal cocaine, intravenous ethanol, or a cocaine-ethanol combination on heart rate, systemic arterial pressure, and coronary arterial dimensions in humans. Methods: Thirty-four subjects with chest pain (27 men and seven women, aged 34 to 67 years) who were referred for catheterization received one of the following pharmacologic interventions: (1) intranasal (2 mL) and intravenous (5 mL/kg) saline (n=8 [group A]); (2) intranasal cocaine (2 mg/kg) and intravenous saline (5 mL/ kg) (n=9 [group B]); (3) intranasal saline (2 mL) and intravenous 10% ethanol (5 mL/kg) (n=9 [group C]); or (4) intranasal cocaine (2 mg/kg) and intravenous 10% ethanol (5 mL/kg) (n=8 [group D]). Heart rate, systemic arterial pressure, left coronary arterial dimensions (by computer-assisted quantitative angiography), as well as blood cocaine, ethanol, and cocaine metabolite concentrations were measured before and 30,60, and 90 minutes after initiation of the intravenous infusions. Results: No hemodynamic or angiographic changes were observed in the group A (saline) subjects. In the group B (cocaine) subjects, the heart rate—systolic arterial pressure product increased by 5% and 10% at 30 and 90 minutes, respectively, and coronary arterial diameter decreased by 14% at these times. In the group C (ethanol) subjects, no hemodynamic changes were noted, but coronary arterial diameters increased by 12%, 11%, and 12% at 30, 60, and 90 minutes, respectively. In the group D (cocaine-ethanol) patients, rate-pressure product increased by 17%, 10%, and 16%, and coronary arterial diameters increased by 7%, 12%, and 13%, at 30, 60, and 90 minutes, respectively. Conclusion: The combination of intranasal cocaine and intravenous ethanol causes an increase in the determinants of myocardial oxygen demand. However, it also causes a concomitant increase in epicardial coronary arterial diameter.(Arch Intern Med. 1995;155:1186-1191) References 1. Lange RA, Cigarroa RG, Yancy CW Jr, et al. Cocaine-induced coronary-artery vasoconstriction. N Engl J Med . 1989;321:1557-1562.Crossref 2. Flores ED, Lange RA, Cigarroa RG, Hillis LD. Effect of cocaine on coronary artery dimensions in atherosclerotic coronary artery disease: enhanced vasoconstriction at sites of significant stenoses. J Am Coll Cardiol . 1990;16:74-79.Crossref 3. Brogan WC III, Lange RA, Glamann DB, Hillis LD. Recurrent coronary vasoconstriction caused by intranasal cocaine: possible role for metabolites. Ann Intern Med . 1992;116:556-561.Crossref 4. Boehrer JD, Moliterno DJ, Willard JE, et al. Hemodynamic effects of intranasal cocaine in humans. J Am Coll Cardiol . 1992;20:90-93.Crossref 5. Isner JM, Estes NAM III, Thompson PD, et al. Acute cardiac events temporally related to cocaine abuse. N Engl J Med . 1986;315:1438-1443.Crossref 6. Smith HWB III, Liberman HA, Brody SL, Battey LL, Donohue BC, Morris DC. Acute myocardial infarction temporally related to cocaine use: clinical, angiographic, and pathophysiologic observations. Ann Intern Med . 1987;107:13-18.Crossref 7. Cregler LL, Mark H. Relation of acute myocardial infarction to cocaine abuse. Am J Cardiol . 1985;56:794.Crossref 8. Schachne JS, Roberts BH, Thompson PD. Coronary-artery spasm and myocardial infarction associated with cocaine use. N Engl J Med . 1984;310:1665-1666.Crossref 9. Rod JL, Zucker RP. Acute myocardial infarction shortly after cocaine inhalation. Am J Cardiol . 1987;59:161.Crossref 10. Weiss RJ. Recurrent myocardial infarction caused by cocaine abuse. Am Heart J . 1986;111:793.Crossref 11. Kossowsky WA, Lyon AF. Cocaine and acute myocardial infarction: a probable connection. Chest . 1984;86:729-731.Crossref 12. Zimmerman FH, Gustafson GM, Kemp HG Jr. Recurrent myocardial infarction associated with cocaine abuse in a young man with normal coronary arteries: evidence for coronary artery spasm culminating in thrombosis. J Am Coll Cardiol . 1987;9:964-968.Crossref 13. Hadjimiltiades S, Covalesky V, Manno BV, Haas WS, Mintz GS. Coronary arteriographic findings in cocaine abuse-induced myocardial infarction. Cathet Cardiovasc Diagn . 1988;14:33-36.Crossref 14. Nanji AA, Filipenko JD. Asystole and ventricular fibrillation associated with cocaine intoxication. Chest . 1984;85:132-133.Crossref 15. Karch SB, Billingham ME. The pathology and etiology of cocaine-induced heart disease. Arch Pathol Lab Med . 1988;112:225-230. 16. Benchimol A, Bartall H, Dresser KB. Accelerated ventricular rhythm and cocaine abuse. Ann Intern Med . 1978;88:519-520.Crossref 17. Young D, Glauber JJ. Electrocardiographic changes resulting from acute cocaine intoxication. Am Heart J . 1947;34:272-279.Crossref 18. Allred RJ, Ewer S. Fatal pulmonary edema following intravenous free-base cocaine use. Ann Emerg Med . 1981;10:441-442.Crossref 19. Wetli CV, Wright RK. Death caused by recreational cocaine use. JAMA . 1979; 214:2519-2522.Crossref 20. Bertolet BD, Freund G, Martin CA, Perchalski DL, Williams CM, Pepine CJ. Unrecognized left ventricular dysfunction in an apparently healthy cocaine abuse population. Clin Cardiol . 1990;13:323-328.Crossref 21. Chokshi SK, Moore R, Pandian NG, Isner JM. Reversible cardiomyopathy associated with cocaine intoxication. Ann Intern Med . 1989;111:1039-1040.Crossref 22. Grant BF, Harford TC. Concurrent and simultaneous use of alcohol with cocaine: results of a national survey. Drug Alcohol Depend . 1990;25:97-104.Crossref 23. National Institute on Drug Abuse, Drug Abuse Warning Network. Annual Medical Examiner Data—1990 . Washington, DC: Government Printing Office; 1991. US Dept of Health and Human Services publication No. (ADM) 91-1840. 24. National Institute on Drug Abuse. Data From the Drug Abuse Warning System (DAWN): Annual Data 1987 . Washington, DC: Government Printing Office; 1988. US Dept of Health and Human Services publication No. (ADM) 88-1584. 25. Rose S, Hearn WL, Hime GW, Wetli CV, Ruttenber AJ, Mash DC. Cocaine and cocaethylene concentrations in human postmortem cerebral cortex. Neuroscience . 1990:16:14. Abstract. 26. Escobedo LG, Ruttenber AJ, Agocs MM, Anda RF, Wetli CV. Emerging patterns of cocaine use and the epidemic of cocaine overdose deaths in Dade County, Florida. Arch Pathol Lab Med . 1991;115:900-905. 27. Altura BM, Altura BT, Carella A. Ethanol produces coronary vasospasm: evidence for a direct action of ethanol on vascular muscle. Br J Pharmacol . 1983; 78:260-262.Crossref 28. Hayes SN, Bove AA. Ethanol causes epicardial coronary artery vasoconstriction in the intact dog. Circulation . 1988;78:165-170.Crossref 29. Pescio S, Macho P, Penna M, Domenech RJ. Changes in total and transmural coronary blood flow induced by ethanol. Cardiovasc Res . 1983;17:604-607.Crossref 30. Abel FL. Direct effects of ethanol on myocardial performance and coronary resistance. J Pharmacol Exp Ther . 1980;212:28-33. 31. Ganz V. The acute effect of alcohol on the circulation and on the oxygen metabolism of the heart. Am Heart J . 1963;66:494-497.Crossref 32. Lasker N, Sherrod TR, Kilam KF. Alcohol on the coronary circulation of the dog. J Pharmacol Exp Ther . 1955;13:414-420. 33. Cigarroa RG, Lange RA, Popma JJ, et al. Ethanol-induced coronary vasodilation in patients with and without coronary artery disease. Am Heart J . 1990; 119:254-259.Crossref 34. Uszenski RT, Gillis RA, Schaer GL, Analouei AR, Kuhn FE. Additive myocardial depressant effects of cocaine and ethanol. Am Heart J . 1992;124:1276-1283.Crossref 35. Gobel FL, Nordstrom LA, Nelson RR, Jorgensen CR, Wang Y. The rate-pressure product as an index of myocardial oxygen consumption during exercise in patients with angina pectoris. Circulation . 1978;57:549-556.Crossref 36. Baller D, Bretschneider HJ, Hellige G. Validity of myocardial oxygen consumption parameters. Clin Cardiol . 1979;2:317-327.Crossref 37. Isenschmid D, Levine B, Caplan Y. A method for the simultaneous determination of cocaine, benzoylecgonine, and ecgonine methyl ester in blood and urine using GC/EIMS with derivatization to produce high mass molecular ions. J Anal Toxicol . 1988;12:242-245.Crossref 38. Reiber JHC, Serruys PW, Kooijman CJ, et al. Assessment of short-, medium-, and long-term variations in arterial dimensions from computer-assisted quantitation of coronary cineangiograms. Circulation . 1985;71:280-288.Crossref 39. Zar JH. Biostatistical Analysis . Englewood Cliffs, NJ: Prentice Hall International Inc; 1974:152-154. 40. Cregler LL, Mark H. Medical complications of cocaine abuse. N Engl J Med . 1986;315:1495-1500.Crossref 41. Jones RT. Psychopharmacology of cocaine. In: Washington AM, Gold MS, eds. Cocaine: A Clinician's Handbook . New York, NY: Guilford; 1987:55-72. 42. Hearn WL, Keran EE, Wei H, Hime G. Site-dependent postmortem changes in blood cocaine concentrations. J Forensic Sci . 1991;36:673-684. 43. Van Dyke C, Barash PG, Jatlow P. Cocaine: plasma concentrations after intranasal application in man. Science . 1976;191:859-861.Crossref 44. Van Dyke C, Jatlow P, Ungerer J, Barash PG, Byck R. Oral cocaine: plasma concentrations and central effects. Science . 1978;200:211-213.Crossref 45. Foltin RW, Fischman MW. Ethanol and cocaine interactions in humans: cardiovascular consequences. Pharmacol Biochem Behav . 1989;31:877-883.Crossref 46. Farre M, de la Torre R, Llorente M, et al. Alcohol and cocaine interactions in humans. J Pharmacol Exp Ther . 1992;260:939-946. 47. Hearn WL, Flynn DD, Hime GW, et al. Cocaethylene: a unique cocaine metabolite displays high affinity for the dopamine transporter. J Neurochem . 1991; 56:698-701.Crossref 48. Dean RA, Christian CD, Sample RHB, Bosron WF. Human liver cocaine esterases: ethanol-mediated formation of ethylcocaine. FASEB J . 1991;5:2735-2739. 49. Hime GW, Hearn WL, Rose S, Cofino J. Analysis of cocaine and cocaethylene in blood and tissues by GC-NPD and GC-ion trap mass spectrometry. J Anal Toxicol . 1991;15:241-245.Crossref 50. Hearn WL, Rose S, Wagner J, Ciarleglio A, Mash DC. Cocaethylene is more potent than cocaine in mediating lethality. Pharmacol Biochem Behav . 1991; 39:531-533.Crossref 51. Caughlin LJ, O'Halloran RL. An accidental death related to cocaine, cocaethylene, and caffeine. J Forensic Sci . 1993;38:1513-1515. 52. Perez-Reyes M, Jeffcoat R. Ethanol/cocaine interaction: cocaine and cocaethylene plasma concentrations and their relationship to subjective cardiovascular effects. Life Sci . 1992;51:553-563.Crossref

Journal

Archives of Internal MedicineAmerican Medical Association

Published: Jun 12, 1995

References