Major Munchausen To the Editor.\p=m-\This letter should alert physicians to another traveling Munchausen syndrome patient who gives a striking history. He is a cultured, intelligent, black man who gives his age as 47, his home as Boston, and has stated variously that he was a SAC pilot, a counterintelligence agent, shot down over Hanoi, etc. He entered Poudre Valley Memorial Hos-

pital, Sept 26, 1974, giving a history of genitourinary pain and bleeding.

An intravenous pyelogram visualized the right kidney, and the left kidney was absent. The patient received meperidine, 75 mg, three times and pentazocine 13 times. Hematuria was evidenced except when the patient was awakened in the middle of the night for a fresh specimen, which was clear. Nurses described him as restless and furtive particularly when urine was collected. When the suspicion of his attending physician was aroused, the patient suddenly checked out of the hospital (leaving a bill of $442.90). He said he was covered by "Champass" (note spelling used by patient), and gave a Social Security number, service number, etc. On Sept 30,1974, the same day he left the hospital, he appeared at the office of a local physi¬ cian, requesting a prescription for dextroamphetamine sulfate (Dexedrine) for narcolepsy, which "had sud¬ denly reoccurred." He gave a history correlated with a great number of scars: gunshot wounds in Hanoi, con¬ cussion, aneurysm surgery, pulmo¬ nary embolus surgery, open heart sur¬ gery. He stated that he was under the care of a cardiologist named Com¬ mander McClure at Bethesda Naval Hospital, Bethesda, Md. Telephone calls to that institution while the patient was still in the physician's office revealed no Dr. McClure. The patient left the physi¬ cian's office rather abruptly when told that reports would need to be sent for and an electroencephalogram obtained. He appeared at another physician's office within an hour. This physician phoned an order for dextroamphetaEdited

by John D. Archer, MD, Senior Editor.

mine to a local drugstore, but the drugstore had already been alerted via telephone "Drug Net" and ad¬ vised the second physician of their suspicions. "Major F." can be described as fol¬ lows: height, 175 cm (5 ft 9 in); weight, 71 kg (157 lb); blood pressure, 134/90 mm Hg. He showed a craniotomy incision, left nephrectomy in¬ cision, left thoracotomy incision, sternal incision, and a number of pig-

mented scars up and down the arms and antecubital area. The Social Security Administration confirmed that a fictitious Social Security number had been used. The patient left Fort Collins for greener pastures and hence we were unable to present this information to him. In view of the recent editorial in The Journal, "The Immortal Baron" (230:90, 1974), it is hoped that the next physician meeting the major will be able to direct him to helpful

psychiatric therapy.

Harry V. Unfug, MD Fort Collins, Colo

Deaths Due to Adverse Drug Reactions To the Editor.\p=m-\There

is wide diver-

vary between 6,000 per year2 and 30,000 to 140,000 per year.3 These estimates have been derived from studies based on analysis of symptoms, signs, and clinical laboratory data, and for the most part have


Gotti1 published [Table 1] based on his analysis of seven large, well-known hospi¬ tals. Of the 2,168 autopsies, Gotti also reported that 179 deaths (8%) "were sus¬ pected or recognized" to have been drugassociated events. Of these 179 deaths, "a drug or drugs was considered to be a direct cause of death in 36 cases" (1.7%). Irey5 has extensively reviewed putative adverse drug reaction cases from a pathologist's point of view, reviewing tissue slides and clinical histories as they were referred to the AFIP in each of 2,537 cases. He has developed a systematic procedure for validating ADR cases. [Table 2] shows his results as applied to the RTRD file of



This table suggests that 38% to 48% of putative ADRs are validated ADRs after combined clinicopathologic analysis. Gotti's 36 deaths from his 1970 survey of 99,029 hospitalized patients is used as the basis for extrapolating to a national 1970 estimate of (36/99,029)-(31,759,000) 11,545 deaths thought to be primarily due to drugs. The AFIP experience in the RTRD that a percentage of 48.4 are validated ADRs yields the figure (0.484)-(ll,545 5,588. Therefore, the range suggested by these values is 5,600 to 11,500 as the extrapolated number of validated ADR deaths of hospitalized persons in the United States in 1970. The following assumptions or limitations are applied to this extrapolation. Clearly, this estimate is based solely on hospital pa¬ tients and does not include any provision for deaths primarily due to drug reactions for persons not hospitalized. The rate of putative ADRs in Gotti's survey is as¬ sumed to be representative of all hospitals. We assume that Gotti's rate of putative ADRs is independent of the autopsy rate. Finally, it is assumed that the AFIP's rate of 48.4% validated ADRs is appropri¬ ate for putative ADRs throughout the United States as well as those specifically referred to the AFIP. =

sity in estimates on morbidity and mortality relating to adverse drug reactions (ADRs). Opinions on the frequency of ADRs in hospitalized patients range from 15% to 40%.1 Estimates on mortality due to ADRs

not included histopathologic

(1) an analysis of the incidence of ADRs as found in autopsies in seven medical centers,1 (2) an analysis of the aggregated experience in the RTRD of all accessioned cases to date (more than 2,500 cases), as to the de¬ gree of certainty of the relationship between the drug(s) and the clinicalpathologic abnormalities, and (3) an in-depth study of 94 cases of phenothiazine-related hepatoses.4 Data on these three studies were submitted to the AFIP statistician, Walter D. Fos¬ ter, PhD, and his analysis and conclu¬ sions are as follows:


studies on biopsy and autopsy material on more than 2,500 cases of alleged drug-reaction cases have been proceeding for the past nine years at the Registry of Tissue Reactions to Drugs (RTRD) at the Armed Forces Institute of Pathology (AFIP). The pathologic findings on these cases were integrated with their associated clinical and laboratory data. Three RTRD studies were used to estimate annual mortality from ADRs:


The rationale for applying the "val¬ idation factor" in the above extra¬ polation is that in analyzing alleged ADR cases in the RTRD, we have found that somewhat less than half of them stand up to the allegation when

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Table 1 .—Admissions, Deaths, and

Autopsies for Calendar Year 1970 (From Gotti1) Survey

Estimated Total in United States*


Data Hospital admissions

or discharges Hospital deaths Autopsies


31,759,000 857,493(2.7%)




*Data obtained from the National Center for Health Statistics, Public Health Service, and as reported by Beanum E, Child MA; Autopsy rates in hospitals, in Kinkaid WH (ed): PAS Reporter. Ann Arbor, Mich, Commission on Professional and Hospital Activities, 1972, vol 10. No. 3.

Drug Reactions (From Irey5)

Table 2.—Adverse

Validated ADRs No. of Putative

_ADRs RTRD file_2,537 Phenothiazineliver study_94

_A_ '

% of Putative No. ADRs 48.4 1,228 36


and Health To the Editor.\p=m-\We agree with the

by Wynder and

and patterns of adverse


(229:1743, 1974) that disease


vention will become the first line of offense in tomorrow's medical care. Through the American Medical Joggers Association (AMJA), we advocate the vigorous exercise and teetotaling life-style of the Olympic marathon runner for everyone, because immunity to coronary heart disease appears to coexist with the ability to cover 42 km on foot. This has been reported in the Masai warriors (N Engl J Med 284:694, 1971) and the Tarahumara Indians (Am Heart J 81:304, 1971). We postulate that it is also true of marathon runners, even though they may have some of the risk factors peculiar to our Western civilization (Science 183:256, 1974). We are encouraged by the article by Kavanagh et al (229:1602, 1974) that showed that the marathon runner's life-style is suitable for some cardiac patients after they have recovered from myocardial infarction. If they can acquire some of this ap¬ parent immunity to heart disease, then "disease prevention" comes one step closer. Society will start thinking


Thus, fusing these several experi¬ in the RTRD, the extrapolated


estimate of annual deaths due to ad¬ drug reactions occurring in the United States recently ranged be¬ tween 5,600 and 11,500.


Nelson S. Irey, MD Armed Forces Institute


all the available clinicopathologic facts are put together. This factor ranged between 38% and 48%, wheth¬ er it was derived from a small num¬ ber of cases (as with the phenothiazine-hepatosis series), or whether it was based on the total aggregation of more than 2,500 cases, which included a wide variety of organs or sites,




of Pathology Washington, DC

1. Gotti EW: Adverse

drug reactions and

the autopsy.

Arch Pathol 97:201-204, 1974. 2. PMA Newsletter, vol 16, No. 29, pp 1-2, 1974. 3. Koch-Weser J: Fatal reactions to drug therapy. N Engl J Med 291:302-303, 1974. 4. Ishak

KG, Irey NS: Hepatic injury associated with

the phenothiazines. Arch Pathol 93:283-304, 1972. 5. Irey NS: Diagnostic problems in drug-induced diseases, in Meyler L, Peck HM (eds): Drug-Induced Diseases. Amsterdam, Excerpta Medica Foundation, 1972, vol 4, pp 1-24.

of "mileage" instead of "medication." The annual physical will be replaced by a quarterly 42-km hike. "Health" can be an individual responsibility— not the product of a "health indus¬


The AMJA physicians encourage their patients to take part in mara¬ thons, and they set a good example by running along with them. We have designed the December Honolulu Marathon for the rehabilitated car¬ diac patient—and the reconditioned middle-aged physician. With this goal in mind, both will keep a close eye on their personal life-style; both should benefit. Thomas J. Bassler, MD Frank P. Cardello, MD American Medical






which exception must be taken. The authors state:

beings are able to tolerate massive quantities of penicillin. The dosage of penicillin is not limited by direct toxic effects of the drug but by the emergence of pathogenic organisms where normal flora are usually present. Human


Penicillin toxicity is

by no means patients receiving dosages of 20 million units of penicillin G per day. It is more likely to occur in patients with renal insufficiency, but the dosage may be toxic in patients with rare


normal renal function. There is a useful review of the subject by Raichle and colleagues in the September 1971 issue of Archives of Neurology.1 This article reported penicillin intoxica¬ tion in a non-uremic patient receiving 20 million units a day, and also re¬ viewed the relevant literature. The signs of penicillin intoxication may not be recognized in acutely ill patients with lobar pneumonia and other infections. These signs include confusional state, generalized muscu¬ lar twitching, myoclonic jerks, and multifocal or generalized convulsions. Physicians should be alerted to the potential neurotoxicity of penicillin G when given in dosages of 20 million units.

Robert A. Fishman, MD of California San Francisco

University 1. Raichle

ME, Kutt H, Louis S, et al: Neurotoxicity of



To the Editor.\p=m-\Therecent article in The Journal, "High-Dose Penicillin Therapy and Pneumococcal Pneumonia" by Brewin et al (230:409, 1974), demonstrated clearly that high doses of penicillin G had no advantage in the treatment of their series of severely ill patients. There is one point in the discussion, however, with


G. Arch Neurol

Painful Teeth and

Dysglycemia To the Editor.\p=m-\Occasionalpublished reference has been made concerning the relationship between diabetes mellitus (hyperglycemia) and percussion-induced pain or sensitivity of the teeth.

However, these




pared to the many publications dealing with oral manifestations of diabetes.

As far



25:232-239, 1971.


could be



published attention has been given to the possible association of a sensitivity to percussion in teeth and overall carbohydrate metabolism (hyperglycemia, normoglycemia, and hypoglycemia). Considering these three aspects of glycemia, there appears to be a distinct relationship between tooth percussion pain and dysglycemia, both hyperglycemia and hypoglycemia.

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Letter: Deaths due to adverse drug reactions.

Major Munchausen To the Editor.\p=m-\This letter should alert physicians to another traveling Munchausen syndrome patient who gives a striking history...
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