CORRESPONDENCE
of ~53 appear to lead to inactivation of the wild-type gene that normally suppresses tumor formation-hence the common designation of ~53 as an “antioncogene” [8]. In different patient8 with AML, mutations of ~53 may be involved in leukemogenesia, reflect severe genetic instability, or simply be an epiphenomenon. Because the role of p53 in AML is not fully understood, Dr. Spino10’8 caveat in using the common label of ~53 as an “antioncogene” in AML is noted.
the patient’s past medical history. The answer is obviously a qualified, ‘yes.’ In fact, the cases in which a 1984; 2: 253-9. judgment was made as to the util9. Dlcke KA. Bayever E, Yao Y, et a/. Antisense p53 ity in case management of having oliionucleotides: potential antileukemic agents [ab an old ECG are shown in Table &act]. Blood 1991; 78 Suppl 1: 383a. IV of Ziemba et al’s article. The Submitted February 28, 1992, and accepted June author8 suggest that availability 11,1992 of baseline ECGs benefited the patient in five of eight cases (PaThe Reply: tients 3, 4, 5, 6, and 8). My own We agree with Dr. Spinolo that it review suggests that the cases of is difficult to estimate the inciPatients 4 and 8, both of which dence of AML in the U.S. As ilshowed that left bundle branch lustration, we note that Dr. SpinDAVID M. MASTRIANNI, MB. block was not present on prior NADINE M. TUNG, M.D. ECGs, were the cases of utility. 010’s calculation of 8,700 cases DANIEL G. TENEN, M.D. per year differ8 from the 11,000 The others either showed atrial Beth Israel Hospital cases per year calculated by one Boston, Massachusetts fibrillation (AF), ischemia, or of the author8 he reference8 [l]. ventricular tachycardia, all of 1. Jandl JH. Blood: textbook of hematology. BosWe believe reporting the inciton: Little Brown, 1987: 633. which, in the presence of symp2. Clii RA. Buckner CD, Thomas ED, eta/. The treatdence of AML as “approximately toms, would have been enough to ment of acute nonlymphoblastic leukemia by alloge10,000 patients” per year avoids admit for treatment or monitorneic transplantation. Bone Marrow Transplant implying precision in what is cer- 1987; 2: 243-8. ing. The rates of AF and the he3. Klingemann HG. Storb R, Fefer A, et al. Bone tainly an inaccurate reporting modynamic and clinical consemarrow transplantation in patients aged 45 years system and provides the reader quences at the time of the ED and older. Blood 1986; 67: 770-6. with a convenient figure to use in 4. Hsu IC, Metcalf RA, Sun T. et al. Mutational hot- evaluation would be more imporcomparing the incidence of AML tant to me than the presence or spot in the p53 gene in human hepatocellular carcinomas. Nature 1991; 3501 427-8. with other diseases. absence of similar finding8 in the The role of allogeneic bone 5. Baker SJ. Fearon ER. Nigro JM, et a/. Chromopast. (The ventricular rates and somes 17 deletions and p53 gene mutations in colomarrow transplantation in the rectal carcinomas. Science 1989; 244: 217-21. blood pressures in AF are not givtreatment of AML remains con- 6. Nigro JM, Baker SJ. Preisinger AC, et a/. Muta- en.) troversial. We have attempted to tions in the p53 gene occur in diverse human tuCertain situations in which a types. Nature 1989; 342: 705-8. present a balanced view of the 7.mourTakahashi prior ECG would be most helpful T. Nau NM, Chiba I, et al. ~53: a frebenefit8 and toxicities of this pro- quent target for genetic abnormalities in lung can- were not encountered: chronic cedure. The toxicity of allogeneic cer. Science 1989; 246: 4914. ST elevation of an old aneurysm bone marrow transplantation in- 8. Finlay CA, Hinds PW, Levine Al. The p53 proto(unless this is what is meant by oncogene can act as a suppressor of transformacreases with age, and the proce- tion. ‘ischemic changes’) or early repoCell 1989; 57: 1083-93. dure is most appropriate for palarization, frequent premature tients under age 45. While an ocventricular contractions, poor Rcasional highly selected patient wave progression, left anterior over the age of 45 will undergo fascicular block (resembling infeIN allogeneic transplantation, the ELECTROCARDIOGRAMS rior infarction and/or anterosepELDERLYPATIENTS IN THE poor reported results and high tal myocardial infarction), EMERGENCYDEPARTMENT toxicity preclude allogeneic marked change in axis, and so transplantation as standard care To the Editor: forth. for the vast majority of older pa- The article by Ziemba et al [l] is By the time someone is 65 or tients [2,3]. fundamentally superfluous. It older and living in a care facility Mutations of the ~53 gene have asks the question of whether a for the elderly, he or she will have been reported in multiple human physician is better off evaluating surely had an ECG, and in my malignancies [4] such as colorecelderly patients in an emergency opinion it is quite appropriate to tal [5], hepatocellular [6], and department (ED) setting with make it available with the rest of lung [7] carcinoma as well a8 in more (i.e., prior electrocardiothe medical record, on each occahematologic malignancies such as gram [ECG]) rather than less sion that a patient come8 to the AML. In most models, mutations (i.e., no prior ECG) data about local ED. Not to do 80 would be kemia. J Exp Med 1986; 1641 75161. 6.Curtis JE. Messner HA, Has&back R, Elhakim TM. McCulloch EA. Contributions of host- and disease-related attributes to the outcome of patients with acute myelogenous leukemia. J Clin Oncol
708
December 1992 The American Journal of Medlclne
Volume 93
CORRESPONDENCE
That is why we included summaries of each case. However, the study protocol instructed the faculty judges to estimate benefit whether or not they thought that the baseline ECG should have influenced the house staff treatment decisions. Therefore, the judges indicated that five of the eight patient8 listed in Table IV benefited from treatment changes even though the baseline ECG would have influenced their MARKG. PERLROTH,M.D. own management decisions in Stanford University School of only three cases. Medicine We agree that,some situations Stanford, California in which baseline ECGs might be 1. Ziemba SE, Hubbell FA. Fine MJ, Burns MJ. Resthelpful were, not encountered ing electrocardiograms as baseline tests: impact on the management of elderly patients. Am J Med during this study. Such findings 1991; 91: 576-83. might have increased the proporSubmitted February 28, 1992, and accepted June tion of patients for whom base11. 1992 line ECGs influenced management. The Reply: We also agree that most elderly Dr. Perlroth was “irked” that we patients will have had prior examined the impact of baseline ECGs performed during their ECGs on the care of elderly pa- lifetimes and that physicians tients in an ED. It is likely that he should have access to them when they are available. However, was also upset when we evaluated the efficacy of routine admission many patients who visit emergency rooms may not have been chest radiographs [ 11, urinalyses [2], and other admission tests [3]. evaluated in that particular hospital before and, therefore, will Nevertheless, we believe that this process of critical rethinking is not have ECGs as part of the essential for defining the role of medical record. Moreover, even if these tests in today’s medical a prior ECG is available, it may practice. Indeed, if groups such be many years old and of limited as the Canadian Task Force on value in making comparisons with a new ECG. Thus, we must the Periodic Health Examination and the United States Preventive ask whether the benefit is worth Health Services Task Force had the cost of performing baseline not reevaluated screening tests, ECGs in elderly patients at reguwe would not have many of the lar (as yet undetermined) intercurrent helpful screening guidevals and ensuring their availabililines [4,5]. ty to physicians. Our data suggest Dr. Perlroth also questioned that this may be the case, at least our judgment about which pa- for patients with cardiovascular tients benefited from treatment disease. However, no one has yet change8 made by the house staff measured all of the costs and savafter they compared baseline and ings attributable to baseline emergency room ECGs. We un- ECGs nor expressed the benefit derstand that physicians may of these tests in units that allow disagree about how particular for comparison with other health baseline ECG findings might af- care technologies. Until investifect their management decisions. gators perform such analyses, the
below the standard of care whether or not the ECG contributes to the management of the patient. Articles of this kind irk me. They are reminiscent of questions that ask whether, in the name of efficiency and economy, we can play a Beethoven symphony with two fewer violinists, since the sound is almost the same. Yes, we can, but it won’t be our best performance.
role of baseline ECGs in the care of elderly patients will remain somewhat speculative. Finally, a few words about Beethoven. In a world of unlimited violinists, we would never restrict their number in a Beethoven symphony. However, in a world of finite resources, we might choose a smaller orchestra if such a choice would mean that more performances could be scheduled and, therefore, more people could attend the symphony. F. ALLANHUBBELL,M.D.,M.S.P.H. SUSANZIEMBA,M.D. University
of California Irvine Medical Center Orange, California
1. Hubbell FA, Greenfield S. Tyler JL. Chetty K, Wyle FA. The impact of routine admission chest x-ray films on patient care. N Engl J Med 1985; 312: 2D9-13. 2. Akin BV, Hubbell FA. Frye EB, Rucker L. Friis R. Efficacy of the routine admission urinalysis. Am J Med 1987; 82: 719-22. 3. Hubbell FA. Frye EB, Akin BV, Rucker L. Routine admission laboratory testing for general medical patients. Med Care 1988; 26: 619-30. 4. Hayward RSA, Steinberg EP. Ford DE, Roizen MF, Roach KW. Preventive care guidelines. Ann Intern Med 1991; 114: 758-83. 5. United States Preventive Health Services Task Force. Guide to preventive health services. Baltimore: Williams and Wilkins, 1989.
METHADONEAND IMMUNE FUNCTION To the Editor: The study by Klimas et al [l] and the letter of Novick and Kreek [2] leave open the question of methadone action on the immune function of intravenous drug users (IVDUs) and ask for longitudinal studies in this field. We evaluated a group of 11 HIV1-seronegative IVDUs undergoing methadone maintenance therapy for 38 months at Servixio Tossicodipendenze, Fatebenefratelli Hospital, Milan, Italy. We noted a 26% decrease in CD4 lymphocytes (initial value 1,228 f 339/n&). We observed exactly the same decrease in a group of 12 HIV-1-seronegative
December 1992 The American Journal of Medicine
Volume 93
709
of ~53 appear to lead to inactivation of the wild-type gene that normally suppresses tumor formation-hence the common designation of ~53 as an “antioncogene” [8]. In different patient8 with AML, mutations of ~53 may be involved in leukemogenesia, reflect severe genetic instability, or simply be an epiphenomenon. Because the role of p53 in AML is not fully understood, Dr. Spino10’8 caveat in using the common label of ~53 as an “antioncogene” in AML is noted.
the patient’s past medical history. The answer is obviously a qualified, ‘yes.’ In fact, the cases in which a 1984; 2: 253-9. judgment was made as to the util9. Dlcke KA. Bayever E, Yao Y, et a/. Antisense p53 ity in case management of having oliionucleotides: potential antileukemic agents [ab an old ECG are shown in Table &act]. Blood 1991; 78 Suppl 1: 383a. IV of Ziemba et al’s article. The Submitted February 28, 1992, and accepted June author8 suggest that availability 11,1992 of baseline ECGs benefited the patient in five of eight cases (PaThe Reply: tients 3, 4, 5, 6, and 8). My own We agree with Dr. Spinolo that it review suggests that the cases of is difficult to estimate the inciPatients 4 and 8, both of which dence of AML in the U.S. As ilshowed that left bundle branch lustration, we note that Dr. SpinDAVID M. MASTRIANNI, MB. block was not present on prior NADINE M. TUNG, M.D. ECGs, were the cases of utility. 010’s calculation of 8,700 cases DANIEL G. TENEN, M.D. per year differ8 from the 11,000 The others either showed atrial Beth Israel Hospital cases per year calculated by one Boston, Massachusetts fibrillation (AF), ischemia, or of the author8 he reference8 [l]. ventricular tachycardia, all of 1. Jandl JH. Blood: textbook of hematology. BosWe believe reporting the inciton: Little Brown, 1987: 633. which, in the presence of symp2. Clii RA. Buckner CD, Thomas ED, eta/. The treatdence of AML as “approximately toms, would have been enough to ment of acute nonlymphoblastic leukemia by alloge10,000 patients” per year avoids admit for treatment or monitorneic transplantation. Bone Marrow Transplant implying precision in what is cer- 1987; 2: 243-8. ing. The rates of AF and the he3. Klingemann HG. Storb R, Fefer A, et al. Bone tainly an inaccurate reporting modynamic and clinical consemarrow transplantation in patients aged 45 years system and provides the reader quences at the time of the ED and older. Blood 1986; 67: 770-6. with a convenient figure to use in 4. Hsu IC, Metcalf RA, Sun T. et al. Mutational hot- evaluation would be more imporcomparing the incidence of AML tant to me than the presence or spot in the p53 gene in human hepatocellular carcinomas. Nature 1991; 3501 427-8. with other diseases. absence of similar finding8 in the The role of allogeneic bone 5. Baker SJ. Fearon ER. Nigro JM, et a/. Chromopast. (The ventricular rates and somes 17 deletions and p53 gene mutations in colomarrow transplantation in the rectal carcinomas. Science 1989; 244: 217-21. blood pressures in AF are not givtreatment of AML remains con- 6. Nigro JM, Baker SJ. Preisinger AC, et a/. Muta- en.) troversial. We have attempted to tions in the p53 gene occur in diverse human tuCertain situations in which a types. Nature 1989; 342: 705-8. present a balanced view of the 7.mourTakahashi prior ECG would be most helpful T. Nau NM, Chiba I, et al. ~53: a frebenefit8 and toxicities of this pro- quent target for genetic abnormalities in lung can- were not encountered: chronic cedure. The toxicity of allogeneic cer. Science 1989; 246: 4914. ST elevation of an old aneurysm bone marrow transplantation in- 8. Finlay CA, Hinds PW, Levine Al. The p53 proto(unless this is what is meant by oncogene can act as a suppressor of transformacreases with age, and the proce- tion. ‘ischemic changes’) or early repoCell 1989; 57: 1083-93. dure is most appropriate for palarization, frequent premature tients under age 45. While an ocventricular contractions, poor Rcasional highly selected patient wave progression, left anterior over the age of 45 will undergo fascicular block (resembling infeIN allogeneic transplantation, the ELECTROCARDIOGRAMS rior infarction and/or anterosepELDERLYPATIENTS IN THE poor reported results and high tal myocardial infarction), EMERGENCYDEPARTMENT toxicity preclude allogeneic marked change in axis, and so transplantation as standard care To the Editor: forth. for the vast majority of older pa- The article by Ziemba et al [l] is By the time someone is 65 or tients [2,3]. fundamentally superfluous. It older and living in a care facility Mutations of the ~53 gene have asks the question of whether a for the elderly, he or she will have been reported in multiple human physician is better off evaluating surely had an ECG, and in my malignancies [4] such as colorecelderly patients in an emergency opinion it is quite appropriate to tal [5], hepatocellular [6], and department (ED) setting with make it available with the rest of lung [7] carcinoma as well a8 in more (i.e., prior electrocardiothe medical record, on each occahematologic malignancies such as gram [ECG]) rather than less sion that a patient come8 to the AML. In most models, mutations (i.e., no prior ECG) data about local ED. Not to do 80 would be kemia. J Exp Med 1986; 1641 75161. 6.Curtis JE. Messner HA, Has&back R, Elhakim TM. McCulloch EA. Contributions of host- and disease-related attributes to the outcome of patients with acute myelogenous leukemia. J Clin Oncol
708
December 1992 The American Journal of Medlclne
Volume 93
CORRESPONDENCE
That is why we included summaries of each case. However, the study protocol instructed the faculty judges to estimate benefit whether or not they thought that the baseline ECG should have influenced the house staff treatment decisions. Therefore, the judges indicated that five of the eight patient8 listed in Table IV benefited from treatment changes even though the baseline ECG would have influenced their MARKG. PERLROTH,M.D. own management decisions in Stanford University School of only three cases. Medicine We agree that,some situations Stanford, California in which baseline ECGs might be 1. Ziemba SE, Hubbell FA. Fine MJ, Burns MJ. Resthelpful were, not encountered ing electrocardiograms as baseline tests: impact on the management of elderly patients. Am J Med during this study. Such findings 1991; 91: 576-83. might have increased the proporSubmitted February 28, 1992, and accepted June tion of patients for whom base11. 1992 line ECGs influenced management. The Reply: We also agree that most elderly Dr. Perlroth was “irked” that we patients will have had prior examined the impact of baseline ECGs performed during their ECGs on the care of elderly pa- lifetimes and that physicians tients in an ED. It is likely that he should have access to them when they are available. However, was also upset when we evaluated the efficacy of routine admission many patients who visit emergency rooms may not have been chest radiographs [ 11, urinalyses [2], and other admission tests [3]. evaluated in that particular hospital before and, therefore, will Nevertheless, we believe that this process of critical rethinking is not have ECGs as part of the essential for defining the role of medical record. Moreover, even if these tests in today’s medical a prior ECG is available, it may practice. Indeed, if groups such be many years old and of limited as the Canadian Task Force on value in making comparisons with a new ECG. Thus, we must the Periodic Health Examination and the United States Preventive ask whether the benefit is worth Health Services Task Force had the cost of performing baseline not reevaluated screening tests, ECGs in elderly patients at reguwe would not have many of the lar (as yet undetermined) intercurrent helpful screening guidevals and ensuring their availabililines [4,5]. ty to physicians. Our data suggest Dr. Perlroth also questioned that this may be the case, at least our judgment about which pa- for patients with cardiovascular tients benefited from treatment disease. However, no one has yet change8 made by the house staff measured all of the costs and savafter they compared baseline and ings attributable to baseline emergency room ECGs. We un- ECGs nor expressed the benefit derstand that physicians may of these tests in units that allow disagree about how particular for comparison with other health baseline ECG findings might af- care technologies. Until investifect their management decisions. gators perform such analyses, the
below the standard of care whether or not the ECG contributes to the management of the patient. Articles of this kind irk me. They are reminiscent of questions that ask whether, in the name of efficiency and economy, we can play a Beethoven symphony with two fewer violinists, since the sound is almost the same. Yes, we can, but it won’t be our best performance.
role of baseline ECGs in the care of elderly patients will remain somewhat speculative. Finally, a few words about Beethoven. In a world of unlimited violinists, we would never restrict their number in a Beethoven symphony. However, in a world of finite resources, we might choose a smaller orchestra if such a choice would mean that more performances could be scheduled and, therefore, more people could attend the symphony. F. ALLANHUBBELL,M.D.,M.S.P.H. SUSANZIEMBA,M.D. University
of California Irvine Medical Center Orange, California
1. Hubbell FA, Greenfield S. Tyler JL. Chetty K, Wyle FA. The impact of routine admission chest x-ray films on patient care. N Engl J Med 1985; 312: 2D9-13. 2. Akin BV, Hubbell FA. Frye EB, Rucker L. Friis R. Efficacy of the routine admission urinalysis. Am J Med 1987; 82: 719-22. 3. Hubbell FA. Frye EB, Akin BV, Rucker L. Routine admission laboratory testing for general medical patients. Med Care 1988; 26: 619-30. 4. Hayward RSA, Steinberg EP. Ford DE, Roizen MF, Roach KW. Preventive care guidelines. Ann Intern Med 1991; 114: 758-83. 5. United States Preventive Health Services Task Force. Guide to preventive health services. Baltimore: Williams and Wilkins, 1989.
METHADONEAND IMMUNE FUNCTION To the Editor: The study by Klimas et al [l] and the letter of Novick and Kreek [2] leave open the question of methadone action on the immune function of intravenous drug users (IVDUs) and ask for longitudinal studies in this field. We evaluated a group of 11 HIV1-seronegative IVDUs undergoing methadone maintenance therapy for 38 months at Servixio Tossicodipendenze, Fatebenefratelli Hospital, Milan, Italy. We noted a 26% decrease in CD4 lymphocytes (initial value 1,228 f 339/n&). We observed exactly the same decrease in a group of 12 HIV-1-seronegative
December 1992 The American Journal of Medicine
Volume 93
709
