Correspondence.

(Letters to the Editor are welcomed. They may report new clinical or laboratory observations and new developments in medical care or may contain comments on recent contents of the Journal. They will be published, if found suitable, as space permits. Like other material submitted for publication, letters must be typewritten, double-spaced, and submitted in duplicate. They must not exceed two typewritten pages in length. No more than five references and one figure or table may be used. See "Information for Authors" for format of references, tables, and figures. Editing, possible abridgment, and acceptance remain the prerogative of the Editors.)

Correction: Generic Substitution

To the Editor: In the abstract of our article, (1) we stated: "Digoxin and levothyroxine tablets are examples of drugs for which no New Drug Applications (NDAs) currently exist." The last sentence of the article notes the first approved NDA for levothyroxine. Regarding digoxin, an NDA was approved on September 30, 1997, for digoxin tablets (Glaxo Wellcome's Lanoxin). Subsequently, a generic digoxin tablet was approved (December 23, 1999, Amide Pharmaceuticals' Digoxin) and rated AB (bioequivalent to Lanoxin). Both of these products are listed in the Orange Book. (2)

Consequently, in the conclusion of our article, our recommendation against generic substitution for Lanoxin tablets is now changed. Prescribers should be confident that substitution of the AB-rated generic version of Lanoxin will produce therapeutically equivalent results.

We apologize to the editors and readers of the Journal for our error and any confusion it may have caused. The overall objective of our article is still our firm conviction: that prescribers should have confidence in the Food and Drug Administration's generic approval process and methodology for bioequivalence determination.

James D. Henderson, PhD, RPh

Department of Physician Assistant Studies

University of South Alabama 

SHAC 4410, 1504 Springhill Ave

Mobile, AL 36604

References

(1.) Henderson JD, Esham RJ: Generic substitution: issues for problematic drugs. South Med J 2001; 94:16-21

(2.) US Department of Health and Human Services, Public Health Service, Food and Drug Administration, Center for Drug Evaluation and Research, Office of Management: Approved Drug Products With Therapeutic Equivalence Evaluations. Washington, DC, US Government Printing Office, 2000, 20th Ed, pp 3-121

An Evolutionary Approach to Medicine

To the Editor: I read with great interest the article by Berlim and Abeche (Berlim MT, Abeche AM: Evolutionary approach to medicine. South Med J 2001; 94:26-32). While on the surface it sounds like a promising approach to pathology, a deeper look reveals that this approach is fraught with the same problems that plague a Darwinian approach to any discipline in science, namely, that it is neither observable nor reproducible. They are correct to point out that Darwinian Medicine is historical in nature, but it would be erroneous to label it as a science, since it fails to meet the two previously mentioned criteria and is therefore not testable. The obvious problem with this approach is that each researcher's conclusions regarding the Darwinian mechanism behind a particular disease state would be equally valid and would be highly dependent upon the researcher's own biases. For example, in their explanation of the relationship between sodium retention and hypertension, Berlim and Abeche state that "Because of the development of agriculture 10,000 years ago, salt intake became even lower, as plants made up 90% of the diet . . . . For this reason, our forefathers developed a mainly renal regulatory mechanism for the conservation of extracellular fluid concentrations." Clearly, anyone with even a rudimentary knowledge about biochemistry should realize that given the vast complexity of our renal regulatory system, a change in our diet would in no way be adequate to account for the myriad of genetic mutations required for this change in renal regulation. Not to mention that the same exact changes would have to occur simultaneously in at least one male and female. This male and female would also have to live in close proximity to each other, be agreeable to reproduce with one another, and have offspring capable of passing on these mutated genes to their progeny. Darwinists tend to conveniently forget that their theory requires mutations, which occur not because of environmental stressors but in spite of them, and which may , in an ideal situation, make the organism better suited to adapt to the environment.

While it is clear that our health is affected by our environment, applying the pseudoscience of Darwinian evolution--a theory that is neither reproducible nor observable--to the discipline of medicine interjects a subjectivity that compromises the integrity of medicine.

Steve M. Skinner, MD

Cullman Dermatology

1205 County Rd 1466

Cullman, AL 35058

Pokemon Contagion 

To the Editor: We read the article on Pokemon contagion (1) with interest and would like to comment on several points. It is not clear from the text whether the authors believe that the initial outbreak of events occurring while watching the original broadcast or the critical extract replayed later was one of photosensitive seizures. Although other causes cannot be excluded for some, both local and outside expert reviews (2,3) suggest that most of those taken to the hospital had evident epileptic seizures, while the remainder had headache, nausea, vomiting, visual changes, and nonspecific abdominal symptoms, highly suggestive of migraine or of photically-induced occipital seizures, a recently recognized and less common epileptic phenomenon that is difficult to discriminate from migraine. (4) These events occurred with no warning or societal exposure as individual acute events in private homes, and a diagnosis of mass psychogenic illness is thus not tenable for this part of the outbreak. The age of the popula tion watching Pocket Monsters was moreover that which is associated with the highest prevalence of EEC abnormalities triggered by flashing light, which is a highly age-related phenomenon estimated to occur in about 5% of asymptomatic children and in about 10% to 20% of those with epilepsy. Clinically evident photosensitive epilepsy is less common. Considering the size of the exposed population and an estimated rate of photosensitive epilepsy of 1:4,000 over all ages, it is in fact surprising that so few acute events occurred.

The age at onset is usually from 6 to 12 years and seems to be dependent on the visual trigger and sex. (5) With increasing triggering of these attacks in daily life by television screens, computers, video games, and other flashing programs, the number of children having visually-induced seizures is increasing, and the age at onset is lower, with more 6- to 8-year-old children having these seizures.

The unusual potency of that particular Pocket Monsters sequence in causing photosensitive epilepti-form EEG activity has been confirmed in other settings. One of us (D.K.N.T.) found that 25 of 35 known photosensitive patients (71%) were even sensitive to that specific 12 Hz colored flashing segment when it was shown on a 100 Hz television, which generally reduces the chance of seizures triggered by the screen. (6) Three other extracts in that Pocket Monsters episode triggered epileptiform EEC activity with the 100 Hz television.

The stimuli that trigger photosensitive seizures also trigger nonepileptic unpleasant symptoms in many individuals especially if they have a history of migraine, in which case these stimuli can even trigger a migraine attack. (7) It would thus not be surprising if school-age children who saw the program, even if they did not see the segment in question, recalled "minor symptoms" of migrainous origin, such as nausea, headache, blurred vision, or vomiting if specifically asked by authority figures; with an estimated 4% of children having migraine, (8) it is similarly not surprising that many would do so.

Regulations have been developed in the European community and in Japan to prevent the broadcast of images likely to cause seizures in susceptible individuals, but there are no such rules in the United States or Canada, though some producers of computer animation follow the United Kingdom guidelines (M. Welman, written communication, February 2000). Isolated screen-triggered seizures occur, though the history may not be obtained at first (experience in Canada suggests that some music videos are a particular problem) and while as pointed out in the article, the risk of these events is less than many people believe, it is real. In the absence of guidelines, individual preventable seizures will occur, and further preventable mass outbreaks can be expected, especially if large audiences of children and adolescents are exposed to such screen images at the same time.

The definition of epidemic hysteria specifies that there be no organic basis for the event. At some time in the Pocket Monsters event, some psychogenic symptoms probably occurred in some individuals. However, we suggest that before this diagnosis can be reached as an explanation for the Pocket Monsters event taken as a whole, renewed attention be devoted to the screen content of the broadcast itself as a trigger of readily explained neurologic events.

Benjamin C. Zifkin, MD, CM, FRCPC 

Epilepsy Clinic

Montreal Neurological Hospital

Faculty of Medicine

Universite de Montreal

Montreal, Canada

Dorothee C. A. Kasteleijn-Nolst

Trenite, MD, MPH, PhD

Epilepsy Centre

Stichting Epilepsie Instellingen

Nederland

Heemstede, The Netherlands

References

(1.) Radford B, Bartholomew R: Pokemon contagion: photosensitive epilepsy or mass psychogenic illness? South Med J2001; 94:197-204

(2.) Japan Ministry of Health and Welfare Study Group: Final Report of the "Study Group on Broadcasting and Audio-Visual Sensory Perception," June 1998

(3.) Harding CFA: TV can be bad for your health. Nati Med 1998; 4:265-267

(4.) Guerrini R, Dravet C, Centon P, et al: Idiopathic photosensitive occipital lobe epilepsy. Epilepsia 1995; 36:883-891

(5.) Kasteleijn-Nolst Trenite DGA: Reflex seizures induced by intermittent light stimulation. reflex epilepsies and reflex seizures. Adv Neurol 1998; 75:98-121

(6.) Ricci 5, Vigevano F, Manfredi M, et al: Epilepsy provoked by television and video games: safety of 100-Hz screens. Neurology 1998; 50:790-793

(7.) Wilkins AJ: Visual Stress. Oxford, Oxford University Press, 1995, p 194

(8.) Lipton RB, Silberstein SD, Stewart WF: An update on the epidemiology of migraine. Headache 1994; 34:319-328