The Editors welcome submissions for possible publication in the Letters section. Authors of letters should: • Include no more than 400 words of text, three authors, and five references • Type with double-spacing • Send with the letter a transfer-of-copyright form (see Table of Contents for location) signed by all authors • Provide a self-addressed envelope if they want to be notified that the letter was received Letters commenting on an Annals article will be considered if they are received within 6 weeks of the time the article was published. Only some of the letters received can be published. Published letters are edited and may be shortened; tables and figures are included only selectively. Authors will be notified only if their letter is accepted. Unpublished letters cannot be returned. Ethics Consultation To the Editors: Drs. La Puma and Schiedermayer (1) describe what they clearly hope will become a new clinical subspecialty—ethics consultation. They claim that this new subspecialty addresses a class of distinctive and important clinical problems—ethical dilemmas. They imply that these problems may overmatch the competence of the primary physician. They claim that a body of theoretic knowledge (biomedical ethics) whose academic foundation offers rational guidance for resolving clinical ethical dilemmas has been established. Finally, they claim that a new, rudimentary clinical discipline (ethics consultation) whose practitioners have "demonstrated ability" in resolving ethical dilemmas has been established. Indeed, the authors legitimize ethics consultation by citing its success. La Puma and Schiedermayer (1) do not define the class of clinical problems that ethics consultants specialize in solving. They neglect to say how such problems are diagnosed. They do not explain what it means to resolve them. Are ethical dilemmas resolved when symptomatic relief occurs (for example, when the physician, the patient, or the patient's representatives stop worrying) or when the underlying cause is removed? They provide no data to support their claim that ethics consultants actually resolve ethical dilemmas. I suggest that we distinguish between pseudo and real dilemmas. We confront only a pseudo dilemma when we are aware that our alternatives have both right-making and wrong-making features. Although one option is really rationally preferable (one option is the "right thing" to do), we may have trouble choosing this option because of self-interest, litigation-related anxiety, institutional politics, or conceptual confusion. We face a genuine ethical dilemma when we have conclusive ethical reasons indicating both that we ought and that we ought not to choose a certain option. Because we cannot both choose and avoid an alternative and because we have no ethical reason for preferring one alternative over another, our ethical framework fails to provide guidance. If genuine ethical dilemmas arise, an accurate diagnosis is the most an ethics consultant can offer. By definition, there are no ethical resources available for resolving genuine ethical dilemmas. The challenge to resolve them must overmatch the competence of the ethics consultant (and everyone else). There is no consensus on whether genuine ethical dilemmas exist or on how we might detect them. Without such a con-

sensus, I am unsure what distinctive service ethics consultants provide; nor do I know how to assess claims of success. Lance K. Stell, PhD Carolinas Medical Center Charlotte, NC 28232-2861 Davidson College Davidson, NC 28036 Reference 1. La Puma J, Schiedermayer DL. Ethics consultation: skills, roles, and training. Ann Intern Med. 1991;114:155-60.

To the Editors: Drs. La Puma and Schiedermayer (1) have extensively described one method of ethics consultation. Institutions that use this model to resolve disputes may find it helpful. The notion of using consultation to resolve "ethical dilemmas" is relatively new (2). Unlike the authors, however, we do not believe that the medical community has reached a consensus about the role that this type of review should play in patient care or has universally accepted the concept of an "ethics consultant." Further, what format best serves case review remains unclear. Ethics consultation at Carolinas Medical Center has taken a different tack. Through our multidisciplinary ethics committee, we have incorporated many of the skills described by Drs. La Puma and Schiedermayer. Realizing that it is often difficult for a committee to act cohesively, we have sought to balance the demand for a timely response to requests for consultation with the value of receiving input from our members. We therefore have formed a consultation service in which review may be provided by either an individual (usually the chairman) or a standing subcommittee of as many as six members (including a medical ethicist, a pastoral services representative, and a physician-in-training). Over 2.5 years, we have received more than 40 requests for consultation. The response from physicians and hospital administration staff has been very gratifying, and the number of consultations has increased each year. Ethics committees have been criticized for attempting to review cases (3). We believe that our approach meets these objections. It is flexible enough to provide a timely response to urgent requests; yet, a broad range of expertise can be deployed, as clinical circumstances require. Mindful of our role as consultants, we have provided a level of involvement that is consonant with the requirements of the case. For example, many ethical dilemmas have a religious foundation (4)—a dimension that La Puma and Schiedermayer (1) fail to address. We have found our pastoral services representative to be invaluable in such situations. Or, if a physician is uncertain about how specific ethical principles should be interpreted, our medical ethicist can provide the necessary instruction. Finally, because our committee is multidisciplinary, we have been able to gain the confidence of both referring physicians and families who otherwise might be suspicious of medical paternalism. We do not claim that our approach to ethics consultation is superior to that proposed by Drs. La Puma and Schiedermayer. We believe that in the appropriate setting, however, it can provide a valuable service to physicians and their patients. Louis L. Brunetti, MD, JD Carolinas Medical Center Charlotte, NC 28232-2861

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References 1. La Puma J, Schiedermayer DL. Ethics consultation: skills, roles, and training. Ann Intern Med. 1991;114:155-60. 2. Purtilo RB. Ethics consultation in the hospital. N Engl J Med. 1984;311:983-6. 3. Siegler M. Ethics committees: decisions by bureaucracy. Hastings Cent Rep. 1986;16:22-4. 4. Special report: religion and medical ethics. Religious beliefs must be considered in decision making. Medical Ethics Advisor. 1990;6:13743. To the Editors: With the availability of medical technology to prolong patients' lives, physicians must make difficult decisions. As a second-year medical student, I support the development of an organized means of helping physicians to resolve ethical dilemmas posed by the use of these technologies. In their article, La Puma and Schiedermayer (1) advocate using a clinical ethics consultant who "gathers information first hand at the bedside" and who can evaluate patients promptly in an emergency situation. This suggestion is not only impractical, but also may not best ensure ethical decision making. Many of the roles proposed for the clinical ethics consultant overlap with those of the physician. Effective communication with patients to determine their concerns, values, and desires is ultimately the physician's responsibility. Unfortunately, communication is often the missing element when ethical dilemmas occur. The physician should be able to discern the patient's views on such issues on artificial respiration and withdrawing and withholding treatment. The services of an ethics consultant should not be necessary to perform this function. In fact, the availability of an ethics consultant may lead the physician to rely on the consultant to communicate with the patient, thus jeopardizing the patient-physician relationship and perhaps leading to compromised patient care. Occasionally, a physician may need assistance in making a particularly difficult decision. In this case, an ethics committee of experts in areas such as law and philosophy would be helpful. It would be difficult for one person to have knowledge and skills equal to those of such a panel. Training in ethical decision making would be valuable for all physicians. With greater awareness of ethical dilemmas, better communication with patients, and greater attention to ethical considerations, physicians themselves could make sound decisions without the aid of a consultant. Ann Edwards University of Florida College of Medicine Gainesville, FL 32610 Reference 1. La Puma J, Schiedermayer DL. Ethics consultation: skills, roles, and training. Ann Intern Med. 1991;114:155-60.

Pulmonary Embolism: Suspicion and Tests To the Editors: In their recent review on diagnosing pulmonary embolism, Kelley and colleagues (1) fail to address a crucial point: In which patients do we suspect pulmonary embolism? The protean manifestations of this "Great Imitator" are often overlooked by the busy clinician; and even if the diagnostic accuracy of a test approaches 100%, it is not useful if it is not ordered in the appropriate clinical settings. Syncope, transient confusion, seizures, transient anxiety, and unexplained tachycardia are but a few of the signs and symptoms of pulmonary embolism that often are not recognized. How many clinicians train themselves to consider the possibility of pulmonary embolism in patients with congestive heart failure, cancer, or trauma or in patients who have had orthopedic surgery. And what strategies can be applied in the case of recurrent "silent" pulmonary embolism culminating in cor pulmonale and irreversible pulmonary hypertension? Thousands of patients die from pulmonary embolism every year, not 808

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because of the inaccuracy of diagnosis or the inadequacy of treatment, but simply because the possibility of pulmonary embolism is not considered often enough. Leonard Sadoff, MD Kaiser-Permanente Hospital Los Angeles, CA 90027 Reference 1. Kelley MA, Carson JL, Palevsky HI, Schwartz JS. Diagnosing pulmonary embolism: new facts and strategies. Ann Intern Med. 1991; 114:300-6. The Tumor Lysis Syndrome To the Editors: We report a case of the acute tumor lysis syndrome arising from the empiric administration of "stressdose" glucocorticoids in a 75-year-old man with an occult lymphoid malignancy. The patient presented somnolent with a history of gradually increasing lethargy and hypotension. In 1979 and 1980, he had had craniotomies for the resection of a recurrent sphenoid meningioma. On admission, he had a blood pressure of 90/60 mm Hg. He was afebrile without evidence of infection. The results of the neurologic examination were nonfocal in the presence of obtundation. The results of the initial laboratory evaluation were significant only for a moderate pancytopenia (hemoglobin concentration, 9.5 g/dL; platelet count, 81 000//xL; leukocyte count, 3.300//xL). The chest roentgenogram obtained on admission was unremarkable, and cranial computed tomography showed no interval changes. Because of the patient's neurosurgical history, hypopituitarism was suspected and empiric therapy with intravenous methylprednisolone was begun. The patient received a total of 625 mg in five divided doses before his serum Cortisol level, obtained on admission, became available 2 days later: It was 0.5 /i,mol/L (17.7 ptg/dL). After initial clinical improvement, the patient had a generalized seizure on hospital day 3 in the setting of acute oligoanuric renal failure. Serum blood-urea nitrogen and creatinine levels had risen from their respective baseline values of 5.7 mmol/L and 159 /nmol/L (16 and 1.8 mg/dL, respectively) on admission to 29 mmol/L and 336 /imol/L (82 and 3.8 mg/dL, respectively); serum phosphorus level was 4.7 mmol/L (14.7 mg/dL); total serum calcium was 1.3 mmol/L (5.3 mg/dL); serum albumin level was 2.2 g/dL; serum uric acid concentration was 1332 /x,mol/L (22.4 mg/dL). Urinary tract obstruction and other causes of acute renal failure were excluded. Urinalysis revealed " s h e e t s " of uric acid crystals consistent with the diagnosis of acute uric acid nephropathy. The combination of acute renal failure, hyperuricemia, hypocalcemia, and hyperphosphatemia suggested a clinical diagnosis of the acute tumor lysis syndrome, and an extensive search for an occult malignancy was begun. A widely disseminated non-Hodgkin lymphoma with features of a small cleaved-cell type (although a more malignant phenotype could not be excluded) was found with biopsy-proved involvement of the skin and bone marrow, abnormal cerebrospinal fluid cytologic results, and a large intraabdominal mass. In the absence of other precipitating events, we conclude that the tumor lysis was induced by the empiric administration of "stress-dose" glucocorticoids during the first 2 days of hospitalization. The acute tumor lysis syndrome is a distinct clinical entity that has been recognized to develop most frequently after aggressive combination chemotherapy of rapidly proliferating neoplasms (1). Although corticosteroid-induced acute tumor lysis syndrome has previously been identified (2), to our knowledge, this report is the first of an acute tumor lysis syndrome in which no underlying neoplasm was known to exist when steroid therapy was administered for an unrelated indication. Christlieb Holler, MD Mandeep Dhadly, MD Massachusetts General Hospital Boston, MA 02114

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References 1. Cohen LF, Balow JE, Magrath IT, Poplack DG, Ziegler JL. Acute tumor lysis syndrome. A review of 37 patients with Burkitt's lymphoma. Am J Med. 1980;68:486-91. 2. Sparano J, Ramirez M, Wiernik PH. Increasing recognition of corticosteroid-induced tumor lysis syndrome in non-Hodgkin's lymphoma. Cancer. 1990;65:1072-3. Increased Endothelin Level after Cyclosporine Therapy To the Editors: The mechanism by which cyclosporine induces acute renal vasoconstriction remains unclear. Endothelin is a novel endothelium-derived vasoconstrictor peptide with a potent and sustained effect (1). Cyclosporine drastically increases the level of endothelin in vivo (in the rat) (2) and in vitro (2, 3). Moreover, the renal constrictive effect of cyclosporine is blunted by endothelin antibody both in isolated rat kidney (4) and in vivo in the rat. These data suggest that endothelin may be an important mediator of cyclosporineinduced renal vasconstriction. We investigated plasma endothelin concentrations in 14 patients (6 men and 8 women) treated with cyclosporine, 5 mg/kg body weight, for idiopathic uveitis. Their age ranged from 30 to 56 years (mean ± SE, 44.4 ± 2.2 years). Plasma creatinine levels ranged from 82 to 140 /umol/L (105 ± 4.4 /rniol/L). Plasma endothelin levels were determined by radioimmunoassay. In these patients, the mean plasma concentration of immunoreactive endothelin was 13 ± 0.8 fmol/mL, a higher than normal level (normal, 8 ± 0.5 fmol/mL; P < 0.001) (n = 20). The mean age of the controls did not differ from that of cyclosporine-treated patients (44 ± 2 years). No correlation was noted among plasma creatinine level, age, treatment duration, and plasma endothelin level. Our results show that circulating endothelin levels are elevated in patients treated with cyclosporine. Whether this elevation is caused by cyclosporine treatment remains unknown. The endothelin released from the damaged endothelium by cyclosporine, however, may possibly contribute to the deterioration in renal function. An increased level of circulating endothelin also might contribute to the systemic hypertension that frequently develops during cyclosporine therapy.

hospital. The interval between admission and the administration of the first antibiotic dose was recorded to the nearest quarter of an hour. Four hundred and thirty-five patients were diagnosed with meningitis from 1978 through 1989. Sixty-three pediatric patients (< 16 years of age) and 24 adult patients with community-acquired meningitis had not previously received antibiotics. The mean interval between admission and the administration of the first dose of antibiotics was 2.42 hours (range, 0 to 9.75 hours) for children and 5.00 hours (range, 1.25 to 12.0 hours) for adults with meningitis. One hundred and seventy-three patients were diagnosed with pneumonia from 1988 through 1989. Only 8 pediatric patients and 34 adult patients had received no antibiotic treatment before admission. The mean interval between admission and the administration of the first dose was 6.22 hours (range, 1.5 to 12.0 hours) in children and 8.01 hours (range, 1.25 to 18.0 hours) in adults. Authorities on infectious diseases have urged starting antimicrobial therapy within 30 minutes of examining patients with an acute presentation of meningitis (2). Other investigators have reported that delays of more than 1 hour are not unusual. Bryan and colleagues (1) found delays in the administration of antimicrobial therapy of 2.1 hours in children and 4.9 hours in adults with meningitis. Nahata and colleagues (3) found that only 5% of 50 children with Hemophilus influenzae meningitis received antibiotics within 1 hour after admission (3). Talan and coworkers (4) evaluated the cases of 122 patients with suspected bacterial meningitis and found a mean delay of 3 hours between patient registration and the initiation of antibiotic therapy. These delays in treatment were similar to those found in our study: 2.42 hours for children and 5.0 hours for adults. There was no indication that our study patients who were treated more recently (1988 to 1989) were treated more rapidly. Adults with pneumonia waited a mean of 3 hours longer than adults with meningitis, and children with pneumonia waited a mean of 3.75 hours longer than children with meningitis for the initiation of antibiotic therapy. Our results show that the initiation of antibiotic therapy often is delayed by several hours in patients with two clearly defined infectious diseases. Robert C. Noble, MD University of Kentucky College of Medicine Lexington, KY 40536-0084

G. Deray, MD A. Carayon, MD P. Le Hoang, MD Hopital Piti6-Salp£triere 75013 Paris, France References 1. Yanagisawa M, Kurihara H, Kimura S, et al. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988;332:441-5. 2. Kon V, Sugiura M, Inagami T, et al. Cyclosporine (cy) causes endothelin-dependent acute renal failure [Abstract]. Kidney Int. 1990; 37:486. 3. Bunchman TE, Brookshire CA. Cyclosporine stimulated synthesis of endothelin by human endothelial cells in tissue culture [Abstract]. Kidney Int. 1990;37:365. 4. Dadan J, Perico N, Remuzzi G. Role of endothelin (EN) in cyclosporine (CsA)-induced acute renal vasoconstriction [Abstract]. Kidney Int. 1990;37:479. Delayed Treatment of Pneumonia and Meningitis To the Editors: Delays in the treatment of community-acquired pneumonia and bacterial meningitis were documented in patients admitted to the University of Kentucky Medical Center, a 461-bed teaching hospital. Patients with a positive culture from a cerebrospinal fluid specimen obtained on hospital day 1 were considered to have community-acquired meningitis (1). Infants with meningitis in the first week of life, patients with hospital-acquired meningitis, and patients who previously had received antibiotics were excluded. Patients with a presumed diagnosis of pneumonia were included for study if they were not being treated with antibiotic therapy at the time of admission and if they had not developed the pneumonia in the

References 1. Bryan CS, Reynolds KL, Crout L. Promptness of antibiotic therapy in acute bacterial meningitis. Ann Emerg Med. 1986;15:544-7. 2. McGee ZA, Baringer JR. Acute meningitis. In: Mandell GL, Douglas RG, Bennett JE, eds. Principles and Practice of Infectious Diseases. 3d ed. New York: Churchill Livingstone; 1990:741-55. 3. Nahata MC, Arnoto RT, Powell DA. Management of pediatric patients with bacterial meningitis in the emergency department. Drug Intell Clin Pharm. 1986;20:796-8. 4. Talan DA, Guterman JJ, Overturf GD, Singer C, Hoffman JR, Lambert B. Analysis of emergency department management of suspected bacterial meningitis. Ann Emerg Med. 1989;18:856-62.

Medical Use of Marijuana To the Editors: We surveyed oncologists to determine whether marijuana in smoked form has a "currently accepted medical use in treatment" to control nausea in patients receiving chemotherapy (1). That point is at issue in an ongoing administrative and legal dispute about whether marijuana in smoked form should be available by prescription along with synthetic THC in oral form (Marinol, Roxane Laboratories, Inc., Columbus, Ohio) (2), of which almost 100 000 doses were prescribed in 1989 (3). In September 1989, the administrator of the Drug Enforcement Administration (DEA) rejected a petition to "reschedule" marijuana in smoked form from Schedule 1 (prohibited) to Schedule 2 (available only by prescription) status under the Controlled Substances Act. This decision rejected the findings of DEA Administrative Law Judge Francis Young who heard

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testimony on the petition. The DEA characterized claims of the medical use of marijuana as a "cruel and dangerous hoax" (4), and DEA Associate Chief Counsel Steven Stone remarked, 4 The Judge seems to hang his hat on what he calls a "respectable minority of physicians.' What percent are you talking about? One half of one percent? One quarter of one percent?" (5). The appeal of the administrator's ruling is now before the U.S. Court of Appeals (Second Circuit). In the spring of 1990, we mailed an anonymous survey to a randomly selected one third of the members of the American Society of Clinical Oncology residing in the United States. Of the 2430 recipients, 1035 (43%) responded. Because of the possibility of response bias, our results only roughly estimate the views of oncologists. Forty-four percent of the respondents reported having recommended the (illegal) use of marijuana for the control of emesis to at least one patient with cancer receiving chemotherapy. Almost half (48%) would prescribe marijuana in smoked form to some of their patients if it were legal. As a group, respondents considered the smoked form to be somewhat more effective than and roughly as safe as the legally available oral form. Of the respondents who expressed an opinion, a majority (54%) thought marijuana in smoked form should be available by prescription. Assuming that all nonrespondents and all respondents without opinions were actually against rescheduling, 13% of oncologists would be for rescheduling; if they were for rescheduling, 85% of oncologists would be for rescheduling. Our survey's results show that oncologists' experience with the medical use of marijuana in smoked form is more extensive and their opinions of it are more favorable than the regulatory authorities appear to have believed. Richard Doblin, MPP Mark A. R. Kleiman, PhD Harvard University, Kennedy School of Government Boston, MA 02138 References 1. AMA Council on Scientific Affairs. Marijuana: its health hazards and therapeutic potentials. J Am Med Assoc. 1981;246:1823-7. 2. Chang A, Shiling D, Stillman R, et al. Delta-9-tetrahydrocannabinol as an antiemetic in cancer patients receiving high-dose methotrexate. Ann Intern Med. 1979;91:819-24. 3. Quarterly Report, December, 1988. Annual Report, December 1989. Somerville, New Jersey: Unimed Pharmaceuticals. 4. 54 Federal Register 53767-53785. 29 December 1989:53784. 5. Slater L. Marijuana: medicine or menace? Spinal Network. 1990; winter:44. Correction: Deaths after Treatment of Hodgkin Disease To the Editors: We have identified an error in data entry that caused us to underestimate the risks for intercurrent death and death from second malignant neoplasms and acute myocardial infarction among survivors of Hodgkin disease (1). The error affected our characterization of survival in the normal population and our subsequent calculations of relative risk. The actuarial survival at 20 years expected for a normal population matched to our Hodgkin disease trial group by age, sex, and race was 91% rather than 67% (revised Figure 2B). The relative risk for death from all causes other than Hodgkin disease in our randomized trial population was 5.3 rather than 1.25, with 12 deaths expected compared with 63 observed (95% CI, 4.0 to 6.7; P < 0.01). The


Revised Figure 2B. Intercurrent disease survival according to initial treatment arm. Survival with radiation (AT? 7) alone (167 patients) and with radiation and adjuvant mechlorethamine hydrochloride, vincristine, procarbazine, and prednisone (MOP[PJ) (159 patients) compared with the actuarial survival expected for an age- and sex-matched population. P-Gehan comparing the treatment arms = 0.6. expected 20-year survival of an age- and sex-matched normal population specifically for malignant neoplasms was 97% rather than 90%. The relative risk for death from a malignancy other than Hodgkin disease was 9.3 rather than 2.35 (CI, 5.9 to 12.9; P < 0.01). The expected 20-year survival specifically for acute myocardial infarction in the matched normal population was 97% rather than 90%. The relative risk for death from myocardial infarction was 3.2 rather than 0.86 times the normal rate (CI, 1.5 to 5.8; P < 0.01). Among the 326 patients participating in randomized, prospective trials comparing radiation therapy alone with standard irradiation and adjuvant MOPP (mechlorethamine hydrochloride, vincristine, procarbazine, and prednisone) chemotherapy, risk for intercurrent deaths exceeded risk for death from Hodgkin disease, was similar for both forms of therapy, and substantially exceeded the mortality expected in the normal population. The revised relative risk calculations underscore our previously expressed concerns about the risks for second neoplasms and premature coronary artery disease among survivors of Hodgkin disease. They reinforce the need for careful evaluation of treated patients and the need for research aimed at decreasing the late effects of therapy without compromising control of Hodgkin disease. We apologize for the error. Steven L. Hancock, MD Richard S. Cox, PhD Saul A. Rosenberg, MD Stanford University Stanford, CA 94305 Reference 1. Hancock SL, Hoppe RT, Horning SJ, Rosenberg SA. Intercurrent death after Hodgkin disease therapy in radiotherapy and adjuvant MOPP trials. Ann Intern Med. 1988;109:183-9.

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Medical use of marijuana.

Letters The Editors welcome submissions for possible publication in the Letters section. Authors of letters should: • Include no more than 400 words...
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