To the Editor:

Using a mortality-only model of smallpox vaccination policies, Bozzette et al (1) calculate that pre-emptively vaccinating the general population saves lives if the probability of a high-impact airport attack is greater than 0.01.

However, vaccine-related mortality generally occurs almost immediately, while vaccine-related protection fully lasts, it is thought, 3 to 5 years (2)(3). Thus, pre-emptive vaccination saves lives if the probability of attack is greater than 0.01 over 3 to 5 years, i.e. if the annual probability is 0.002 to 0.003 or higher. The 482 deaths predicted to result from a policy of pre-emptively vaccinating the population approximately equal the deaths from lightning strikes in the United States during a 5-year period (4).

Furthermore, although the attack scenarios used in the model were developed in consultation with experts, the evil ingenuity of some humans should not be underestimated. Attack plans targeting entire cities certainly exist (5). Prudent policy-making would, therefore, model an “Attack Scenario X” which is more lethal than the worst attack experts can publicly discuss.

These considerations make a policy of pre-attack population vaccination more attractive.

To the Editor:

The Journal’s editorial oversight of Mack’s analysis of smallpox (1) was so flawed that the article should have been presented as medical history, not as a contribution to biodefense policy.

Mack describes “average” smallpox characteristics in naturally occurring outbreaks. This represents a best-case scenario. The next outbreak will not be natural, and it may not be average.

The Soviets, for example, weaponized a highly virulent variola strain (2) and treated their variola “with plastics and resins to increase its potency and longevity in the air” (3). Responsible policy cannot, therefore, assume that attacks will use an average strain and natural delivery of variola.

Mack’s suggestion that “the media should provide more information about the dangers of vaccination” is exactly opposite the true need. In the same issue, Blendon et al (4) report that 25% of Americans believe death is a “likely” outcome of smallpox vaccination. The Journal should have caught the contradiction, and should have used its bully pulpit with lay readers and journalists to provide reminders of the safety of vaccination in appropriate populations.

To the Editor:

If this were 1903, I would diagnose ochronosis in the woman shown in the April 5 “Medical Mystery” (1). It would be the eighth case in the world’s literature. But if this were 1904, and if I were William Osler (alas!), then I would consider alkaptonuria as an additional diagnosis.

Before 1904, the diagnosis of alkaptonuria applied only to urine. Chemical properties, not color, made the diagnosis. A link with ochronosis had been proposed (2), but Osler was the first to describe ochronosis and alkaptonuria coexisting in patients, thereby bringing alkaptonuria “within the realm of the clinical physician” (3). Today, ochronotic pigmentation is considered a feature of the metabolic disease alkaptonuria (4).

Osler’s paper also lets us ponder the man and his times. Osler describes the examination of his index patient, then states: “As he left the room my attention was directed to the deep blue color of the inner surface of the ears” (3). Even if we were all Oslers (alas!), most physicians are now too busy completing reimbursement forms to watch their patients walk out of the examination room.

To the Editor:

Because it emphasized a bedside approach rather than millisecond dissections of electronic catheter tracings, I found Drs. Zimetbaum and Josephson’s discussion of symptoms and circumstances associated with palpitations refreshing (1). They did not mention, however, the tachycardia-polyuria syndrome.

As described in the 1960s, polyuria occurs in approximately half of patients with paroxysmal supraventricular arrhythmias faster than 110 beats per minute lasting for 20 or more minutes when left ventricular failure and stenotic valvular lesions are absent (2,3). Why the syndrome is so underreported to physicians is unclear. Diuresis typically begins 20 to 60 minutes after the onset of the arrhythmia, is most intense in the first 1 to 2 hours, and may last as long as 8 hours if the arrhythmia lasts that long (2,3,4). It is unusual for polyuria to occur before the palpitation or with ventricular arrhythmias.

The syndrome’s physiology is incompletely known, but seems, in part, to depend on a rise in atrial pressure causing release of atrial natriuretic peptides. Of note, in a recent series of 13 patients with atrioventricular nodal reentrant tachycardia (AVNRT), 12 had associated diuresis (5). Compared to other atrial arrhythmias, the rise in atrial pressure was greatest in AVNRT, as might be expected from symptoms typical of this disorder: cannon A waves and a sensation of pounding in the neck (1).

Thus, the tachycardia-polyuria syndrome is probably a useful indicator of a supraventricular tachycardia, and perhaps AVNRT in particular.

To the Editor:

Speculations regarding Creutzfeldt-Jakob disease (CJD) acquired from beef containing the infectious agent that causes bovine spongiform encephalopathy [1] have resulted in dramatic health policy measures and serious concerns in the lay public about dietary beef intake in Britain. We believe these concerns are out of proportion to the actual risk of CJD, especially when compared to other established risks of beef consumption, such as the development of coronary heart disease (CHD). We therefore sought to estimate a beef-eater’s risk of CJD and CHD based on currently available data.

The ten cases of CJD became manifest over a 20 month span in 1994-1995 [1]. If we suppose a uniform incubation period of 10 years for CJD, then all 10 cases were infected during a 20 month period in 1984-1985, when the mean beef intake among the 56 million Britons was 181.5 g/person/week [2] (roughly equivalent to two hamburgers per week). Assuming the attack rate remains constant, an average Briton would have a 1 in 933,000 chance of developing CJD from 10 years of beef-eating. The risk per hamburger is roughly 1 in one billion.

To determine the beef-attributable risk of CHD, we first calculate the change in serum cholesterol that results when the fat and cholesterol in lean beef [3] are consumed in place of isocaloric carbohydrate or protein. Using the average daily caloric intake in Britons (2040 kcal) [2], the Hegsted equation [4] predicts a 2.1 mg/dl increase in serum cholesterol when 181.5 g beef/week are consumed. For a 30 year-old non-smoking, non-diabetic man with a total cholesterol of 150 mg/dl, an HDL cholesterol of 45 mg/dl, and a systolic blood pressure of 120 mmHg, the Framingham equation [5] predicts that a 2.1 mg/dl increase in serum cholesterol sustained over 10 years raises the risk of CHD during this period by 1 chance in 5300. Thus the CHD/CJD relative risk is approximately 175!

Although our calculations are approximations at best, they clearly show that the risk from fat and cholesterol in beef is, for most of the adult population, orders of magnitude greater than the risk from neurotropic particles contained therein. Other diseases linked to fat intake, such as stroke and colon cancer, have not been considered here. Based on these data we believe that beef-eaters should care for their coronaries, rather thsn perseverate on prions.