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The Editors welcome submissions for possible publication in the
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Letters commenting on an Annals article will be considered if they
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letters cannot be returned.
Fever: Blessing or Curse?
To the Editor: Although I agree with Dr. Mackowiak (1) that it
is useful to view biological processes such as fever from an
evolutionary perspective, his hypothesis is based on a misunderstanding of the process of evolution by natural selection. His
assumption that the essence of evolution is "preservation of the
species rather than the survival of the individual" has no basis in
evolutionary theory.
Genes are "selfish" (2). Their sole "purpose" is to make copies
of themselves. If a gene's phenotype confers a survival advantage
that allows an individual to reproduce, then more copies of the
gene are produced. Genetically determined altruistic behavior is
seen only when it benefits related individuals who are likely to
carry the same gene. Thus, a gene may reduce an individual's
survival if it sufficiently increases the survival of other individuals
carrying the same gene. Such sacrifices are not made for "the
species." If the first genes for fever decreased infection-related
mortality, they would have been perpetuated through natural
selection. If, however, they increased infection-related mortality
for the individual but reduced contagion and subsequent mortality for unrelated individuals, these genes would not receive the
benefit of natural selection.
It is not necessary for a biological system such as fever to be
adaptive in all situations for it to be evolutionary advantageous.
For example, when the genes for the renin-angiotensin system
first appeared, they were presumably selected because of their
adaptive responses to extracellular volume depletion (for example, from infectious diarrhea or acute traumatic blood loss) in
individuals who could still reproduce. Fluid retention is, of
course, maladaptive in cardiac dysfunction when it results in
pulmonary congestion and hypoxemia. Few individuals experience congestive heart failure before or during their reproductive
years, so no evolutionary survival disadvantage results from the
maladaptation. Thus, biological processes such as fever or the
renin-angiotensin system can be adaptive in certain circumstances and maladaptive in others and remain evolutionary advantageous.
Eric Schwam, MD
University of Massachusetts Medical Center
Worcester, MA 01655
1. Mackowiak PA. Fever: blessing or curse? A unifying hypothesis. Ann
Intern Med. 1994;120:1037-40.
2. Dawkins R. The Selfish Gene. New York: Oxford University Press;
To the Editor: In his article (1), Dr. Mackowiak tries to explain
why a human would evolve to develop a sometimes beneficial,
other times harmful trait such as fever. He argues that one way
to approach the concept is to understand evolution at the species
level rather than at the individual level. Thus, a person prematurely killed by a high fever may not benefit from the fever, but
other members of the species, who will no longer be exposed to
the illness, will benefit (a sort of evolutionary altruism).
The problem with this explanation is that most evolutionists,
including Darwin, have argued that in almost all cases, evolution
occurs at the level of the individual. As Stephen Jay Gould (2)
points out:
Most evolutionists would now admit that group selection can occur in certain special situations (species
made of very many discrete, socially cohesive groups in
direct competition with each other). But they regard
such situations as uncommon if only because discrete
groups are often kin groups, leading to a preference
for kin selection as an explanation for altruism within
the group.
In other words, suppose I die of a fever in a way that allows
my siblings to live. My death will have promoted the ongoing life
of individuals who share many of my genes. In that respect,
whatever genetic trait caused me to die altruistically will (to the
extent that my siblings share the trait) be passed on to future
generations, as will many of my genes. This altruism, then, is not
evidence of evolution at the species level but at the individual
level. My death has served to pass on some amount of my
genetic information. Suppose, instead, that my act of altruism
saves the lives of persons unrelated to me. What will then happen to my genes? Because I have died, I no longer have a chance
to pass on my genes. And because people unrelated to me are
unlikely to share this gene, the gene that caused my altruism will
not be propogated. Instead, others who do not have the gene will
survive, and their genes will be propogated. Evolution is generally not altruistic.
Perhaps a simpler explanation could be applied to the evolution of fever. Fever sometimes hurts, but more often it helps.
Thus, one is more likely to survive (and pass on one's genes) if
one can mount a fever than if one cannot. Evolution is not a
perfect process. Sickle cell disease exists because it more often
helps persons in areas where malaria is common than it hurts
them. Why should fever be any different?
Peter A. Ubel, MD
University of Pennsylvania School of Medicine
Philadelphia, PA 19104
1. Mackowiak PA. Fever: blessing or curse? A unifying hypothesis. Ann
Intern Med. 1994;120:1037-40.
2. Gould SJ. The Panda's Thumb: More Reflections in Natural History.
New York: W.W. Norton; 1980:89.
To the Editor: There is an error, although not a fatal one, in
Dr. Mackowiak's thought-provoking application of evolutionary
principles to fever (1). He argues that the adverse effects of
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overwhelming sepsis can be understood "if one accepts preservation of the species rather than survival of the individual as the
essence of evolution." Preservation of the species is not the
essence of evolution, and neither is survival of the individual. In
a sense, the unit of evolution is the individual gene. This approach was used by W. D. Hamilton (2, 3) to explain the seemingly paradoxical evolution of altruism and is now an accepted
aspect of modern evolutionary theory.
Hamilton's key insight was the observation that an individual's
genes can be passed on to the next generation, not only in
offspring of that individual but also in offspring of that individual's siblings and cousins. It is therefore possible for a gene that
tends to greatly increase the reproductive success of relatives
while slightly decreasing the reproductive success of the individual to increase in frequency in successive generations and eventually to become predominant in the population.
A similar argument can be made about the response to overwhelming sepsis. This response evolved during a time when extended families presumably lived in close proximity. The rapid
death of an individual with overwhelming infection could abort
an epidemic that could damage the individual's children, siblings,
and cousins. Accordingly, genes associated with such a febrile
response would increase in frequency. This evolutionary process
acts at the level of the individual gene and not on the species as
a whole.
Robert A. Fischer, MD
Albert Einstein Medical Center
Philadelphia, PA 19141
1. Mackowiak PA. Fever: blessing or curse? A unifying hypothesis. Ann
Intern Med. 1994;120:1037-40.
2. Hamilton WD. The genetical evolution of social behavior: I. JTheor
Biol. 1964;7:1-16.
3. Hamilton WD. The genetical evolution of social behavior: II. J Theor
Biol. 1964;7:17-52.
To the Editor: I read with interest Dr. Mackowiak's article (1).
In his troubling conclusion he implies that fever may have a
salutary benefit for the species that overrides the needs of the
individual. It is disconcerting when a physician or scientist attributes a teleologic role to either a disease or a biological
response. Scientifically, it must be considered fanciful to assume
that fever has an evolutionary basis in promoting survival of a
"hopelessly infected and potentially contagious individual
The author proposes that fever acts as an evolutionary stimulus
to promote the survival of a species at the expense of an individual. On the surface, his assumptions seem plausible and are
reminiscent of hypotheses generated by the early racial hygienics
movement, which presented as axiomatic the belief that disease
was useful in eliminating those who were ill or not fit in order to
promote the survival of an immunologically strong species (2, 3).
No such theories of the influence of disease on the social biology
of humans have ever been subjected to careful analysis or testing.
Although it may seem far-fetched to a modern audience, unsupported theories of the utility of fever or infection to strengthen
the more "gifted" elements of the species have historically led to
a scientific and medical concept of heredity with profound political and moral implications (4).
I encourage the editors of this and other prestigious journals
to consider seriously the broader implications of unsupported
perspectives that may often have as their origins unsupported
genetic or social principles, especially in the light of the history
of such theories in the 20th century (5).
Gary Schiller, MD
University of California, Los Angeles, School of Medicine
Los Angeles, CA 90024
1. Mackowiak PA. Fever: blessing or curse? A unifying hypothesis. Ann
Intern Med. 1994;120:1037-40.
2. Ploetz A. Die Tuchtigkeit unserer Rasse und der Schutz der Schwachen.
Berlin; 1895:116-44.
3. Haycraft J. Social Darwinism and Race Betterment. London; 1895:51-7.
4. Ploetz A. Sozialpolitik und rassenhygiene. Archiv fur Soziale Gesetzgebung und Statistik. 1902;17:393-425.
5. Proctor RN. Racial Hygiene: Medicine Under the Nazis. London Harvard University Press; 1988.
To the Editor: Dr. Mackowiak (1) proposes that the "preservation of the species rather than survival of the individual [is] the
essence of evolution." This concept is logically untenable. Evolution results in the formation of new species and in the extinction of others. If species are preserved, no evolution occurs.
Richard Dawkins' book The Selfish Gene (2) is a cogent polemic against "the erroneous assumption that the important thing
in evolution is the good of the species (or the group) rather than
the good of the individual (or the gene)."
Dr. Mackowiak advances the hypothesis that "the febrile response and its mediators might have evolved both as a mechanism for accelerating the recovery of infected individuals with . . .
mild to moderately severe systemic infections and for hastening
the demise of hopelessly infected individuals, who pose a threat
of epidemic disease to the species." However, he then undermines his hypothesis by identifying fever as adaptive in such
contagious epidemic (or endemic) diseases as poliovirus, Coxsackie B virus, rabies, and herpesvirus but as maladaptive in
gram-negative bacteremia, which is never epidemic.
If fever is adaptive for most individuals, then individual selection will maintain this trait in the population, and no need exists
to invoke group selection as an explanation for the persistence of
this trait. If fever is maladaptive for most individuals, can group
selection explain the widespread phenomenon of febrile response
to infection? This is unlikely, given that group selection is an
extraordinarily rare evolutionary phenomenon that occurs in special circumstances that do not seem present here (3).
It would be more fruitful to view the maladaptive aspects of
fever in the host as side effects of the pathogen's struggle to
maximize its own reproductive fitness. Some symptoms of disease
(for example, diarrhea in cholera and phlegm production in
respiratory infection) are clearly maladaptive for the host but
favor the pathogen's transmission to other hosts, thereby enhancing the pathogen's reproductive fitness (4).
Richard B. Johnson, MD, MPH
Udhailigah 31311
Saudi Arabia
1. Mackowiak PA. Fever: blessing or curse? A unifying hypothesis. Ann
Intern Med. 1994;120:1037-40.
2. Dawkins R. The Selfish Gene. New York: Oxford University Press;
3. Johnson RB. The group selection of variola minor in the Americas: an
anthroponootic analogue of the myxomatosis epizootic in Australia.
Med Hypoth. 1986;19:341-4.
4. Johnson RB. Human disease and the evolution of pathogen virulence.
JTheor Biol. 1986;122:19-24.
To the Editor: Dr. Mackowiak (1) presents the interesting hypothesis that "if one accepts preservation of the species, rather
than survival of the individual, as the essence of evolution, fever
and its mediators might have evolved . . . for hastening the elimination of fulminantly infected individuals who pose a threat of
epidemic disease to the species."
This hypothesis uses the "species benefit fallacy" (2). As evolutionary biologists have shown (3), natural selection can only act
on the individual (or on groups of closely related kin), not on the
species. Any individual who died to preserve the species would
fail to leave his or her traits to subsequent generations. Individuals without the trait that led to early death would leave more
offspring, and the trait would tend to disappear from the population. The "essence of evolution" rests in the fact that individuals leave different numbers of surviving offspring according to
their individual evolutionary fitness. The current consensus is
that a trait will not evolve to preserve the species (4).
Daniel B. Hrdy, MD, PhD
University of California, Davis, Medical Center
Sacramento, CA 95817
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1. Mackowiak PA. Fever: blessing or curse? A unifying hypothesis. Ann
Intern Med. 1994;120:1037-40.
2. Trivers R. The group selection fallacy. In: Social Evolution. Menlo
Park, New Jersey: Benjamin/Cummings; 1985:76.
3. Williams GC. Adaptation and Natural Selection. Princeton, New Jersey:
Princeton University Press; 1966.
4. Krebs JR, Davies NB. An Introduction to Behavioural Ecology. Oxford:
Blackwell Scientific; 1993:14.
To the Editor: In his fascinating article, Mackowiak (1) proposes an attractive hypothesis for the continuing debate on the
teleologic question of fever as a friend or an enemy. This hypothesis reconciles the results of experimental and clinical studies
that show fever both as friend and foe. However, it is important
to note that in some of the studies attributing organic damage to
fever, the damage is actually caused by hyperthermia, a wellknown mechanism of injury (2). In hyperthermia, no defenses
against aggression are activated, liberation of cytokines is not
implicated, and prostaglandin synthesis is not involved. Instead, a
dysfunction of thermoregulatory mechanisms leads to a temperature sometimes sufficient to cause thermal damage. Although
fever is a manifestation of a functional thermoregulatory system,
hyperthermia is characteristic of a disarranged one. Examples of
hyperthermia are heat stroke, anhydrosis, occlusive clothes, hypothalamic injuries, and malignant hyperthermia. A difference
also exists experimentally between induced hyperthermia and
induced fever; the former is achieved by warming and the latter
by pyrogen injection.
Although I agree with Dr. Mackowiak's unifying hypothesis,
some of the apparent contradictions concerning the organic effects of fever can be caused by a lack of distinction between fever
and hyperthermia. It is clear that the latter must be suppressed,
whereas febrile response can contribute to face aggression.
Alberto Lifshitz, MD
University of Mexico
Mexico City 06725
1. Mackowiak PA. Fever: blessing or curse? A unifying hypothesis. Ann
Intern Med. 1994;120:1037-40.
2. Stitt JT. Fever versus hyperthermia. Federation Proceedings. 1979;38:
In response: I am grateful to each of the authors for their
interest in my article and for their thought-provoking reflections
on theories of evolution. Of the questions they raise in their
letters, the most perplexing concerns the basic unit of evolution.
Dr. Schwam maintains that the basic unit of evolution is the
gene. Genes certainly play a fundamental role in the process;
however, the proposition that "genes making copies of themselves" is the essence of evolution, although provocative in its
simplicity, does nothing to enhance our understanding of why
some genetic traits survive and others disappear during evolution.
It also does not explain why fever, a biological process controlled
by many genes, protects the host in certain situations and harms
it in others. Similarly, if survival of the individual is the essence
of evolution, why would a physiologic response (fever), maintained for more than 400 million years of the evolutionary process, accelerate the demise of individuals with sepsis? Perhaps, as
Dr. Ubel suggests, the occasional pernicious effects of fever
simply reflect the fact that evolution is an imperfect process. I
cannot disprove this hypothesis but find it intellectually unsatisfying.
I am nevertheless grateful to Dr. Ubel for his discussion of
group selection and to Dr. Fischer for sharing "Hamilton's key
insight . . . that an individual's genes can be passed on to the next
generation, not only in the offspring of that individual but also in
that individual's siblings and cousins." I believe that such group
selection is precisely the means by which the febrile response
might have established itself within the gene pool of primitive life
Phylogenetic data suggest that the febrile response first
emerged in the common ancestor of annelids and arthropods.
Thus, the evolutionary struggle that ultimately established fever
as an almost universal response of higher animals occurred hundreds of millions of years before humans emerged. If closely
related subpopulations of this early life form derived some survival advantage from the genetic trait, then, according to our
current understanding of evolution, the trait itself would probably have been preserved from one generation of the organism to
the next.
I believe that the detrimental effects of fever during sepsis
could only have been advantageous—and therefore likely to have
been preserved during evolution—if the welfare of the group
rather than of the individual were the primary determinant in the
evolutionary process. If so, hastening the death of an individual
with sepsis during an epidemic might have been a means by
which a subpopulation of the early life form limited the spread of
epidemic diseases among its members. If it was effective in this
regard and if the epidemic disease was particularly virulent, the
capacity of fever for accelerating the elimination of individuals
with sepsis might have enabled a closely related subpopulation
(that is, siblings and cousins) possessing the trait to survive the
epidemic, whereas other unrelated subpopulations not possessing
the trait died.
I agree with Dr. Schiller that his proposal is "far-fetched." I do
not believe, nor am I proposing, that the primary function of the
febrile response is to weed crippled persons from the species. Its
primary function is to accelerate recovery from infection. Nevertheless, considerable experimental evidence indicates that the
febrile response increases mortality in patients with gram-negative sepsis, a condition that, contrary to Dr. Johnson's contention, can be highly contagious and extremely lethal if the gramnegative bacillus happens to be a bacterium such as Pasteurella
pestis. Fortunately, such epidemic infections are rare in humans,
although they had a devastating influence earlier in our history.
If similar epidemics plagued the primitive precursor of annelids
and anthropods, the darker side of fever might have evolved and
established itself widely within the gene pool as a result of the
process of group selection so succinctly described by Dr. Ubel.
Philip A. Mackowiak, MD
Department of Veterans Affairs Medical Center
Baltimore, MD 21201
Noninvasive Ventilation
To the Editor: We read with interest Meyer and Hill's excellent
review on noninvasive positive pressure ventilation (1). The authors provide some selection guidelines for its use that are based
on reports in the literature. According to those guidelines, noninvasive positive pressure ventilation should be avoided in patients with acute respiratory failure associated with hemodynamic
We have noted that not all the cited reports included information on the hemodynamic status among their selection criteria
in patients with acute disease. Further, when excluding hemodynamically unstable patients, the authors failed to define hemodynamic stability.
It is well known that conventional mechanical ventilation by
endotracheal intubation may seriously alter hemodynamic status
(particularly when external positive end-expiratory pressure, invasive positive pressure ventilation, or intermittent mechanical
ventilation is used) (2). Hemodynamic status is less affected in
patients treated with pressure support ventilation (3). We know
of no reports of similar adverse effects of noninvasive positive
pressure ventilation when nasal or facial masks are used. Therefore, could this type of ventilation represent a possible alternative ventilatory treatment in patients with hemodynamic instability?
We used bilevel positive airway pressure ventilation (BiPAP;
Respironics, Inc.) through a nasal mask to ventilate 57 consecutive, unselected patients with acute respiratory failure who were
unresponsive to oxygen and medical therapy alone. We applied
noninvasive positive pressure ventilation for almost 22 hours
daily, with a median inspiratory positive airway pressure of 15 cm
H 2 0 (maximum, 20 cm H 2 6 ; minimum, 8 cm H 2 0 ) and a
median expiratory positive airway pressure of 4 cm H 2 0 (range,
8 cm H 2 0 to 3 cm H 2 0 ) . Seven patients had hypotension (systolic blood pressure <100 mm Hg; mean, 88 ± 6 mm Hg), 11
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had radiologic and clinical findings of pulmonary edema, 20 had
edema of the legs; 38 had tachycardia; 21 had hypertension; and
20 had arrhythmias. After 24 hours of BiPAP ventilation, only
three patients with initial normal blood pressure and none of
those with hypotension showed a decrease of 15 mm Hg or more
in their mean blood pressure. None failed to respond to BiPAP.
Of the 57 patients, 39 were successfully ventilated with BiPAP,
and 18 patients required intubation or died. At the time of
hospitalization, we found no significant variations in blood pressure, heart rate, presence of edema of the legs, arrhythmias,
respiratory rate, or blood gas values between patients successfully
ventilated with BiPAP and those who failed to respond to treatment. Only the prognostic score of the Acute Physiology and
Chronic Health Evaluation III (APACHE III) was significantly
higher in patients who failed to respond to noninvasive positive
pressure ventilation (P < 0.01). Even in our previous report of 30
patients with severe exacerbations of chronic obstructive pulmonary disease, we found the APACHE III score to be the only
determinant of success or failure of bilevel noninvasive positive
pressure ventilation (4).
Clearly, our experience does not have the power of a perfectly
designed study. It could, however, be of interest because it presents a series of unselected patients, including those who were
hemodynamically unstable. Hemodynamic instability is often associated with exacerbation of obstructive airway disease and
other causes of respiratory distress in patients with auto-positive
end-expiratory pressure, even in the absence of pulmonary
edema (5). Clinical experience suggests that in acutely ill patients, there is often not enough time to evaluate the stability of
the hemodynamic status before a decision to ventilate must be
made. We therefore believe that when intensive care is available
and promptly administered, noninvasive positive pressure ventilation may be attempted as a first-step treatment, even in hemodynamically unstable patients.
Marco Confalonieri, MD
Stefano Aiolfi, MD
Alessandro Scartabellati, MD
Hospital of Crema
1-26013 Crema
positive pressure ventilation, and the success rate of approximately 66% compares favorably with those of other similar series. We maintain, however, that some patients with "hemodynamic instability" remain poor candidates for this treatment.
These include patients with not only hypotension but also with
evidence of inadequate organ perfusion not easily reversed by
fluid resuscitation or pressor agents. In such patients, intubation
and paralysis may be necessary to minimize the energy consumption by respiratory muscles, and application of noninvasive positive pressure ventilation could be deleterious by delaying the use
of more definitive therapeutic measures.
Nicholas S. Hill, MD
Brown University
Rhode Island Hospital
Providence, RI 02903
Thomas Meyer, MD
Thomas Jefferson University
Philadelphia, PA 19107
Coelenterate Sting
To the Editor: Could there be other causes for the clinical problems noted in the patient in the report by Garcia and colleagues
(1)? Although they report no blood culture results, it would seem
that infection with Vibrio or other marine organisms might be
possible. The ulcerations pictured in Garcia and colleagues' Figure 1 certainly appear similar to those I have seen in patients
with V. vulnificus sepsis. Addition of dexamethasone to a regimen
of antibiotics that does not cover Vibrio organisms raises the
question of multiorgan failure as a result of disseminated bacterial infection from sea water. Previous dives in a similar environment with coelenterate exposure could have resulted in the patient's IgG titers.
Steven L. Oscherwitz, MD
Tempe, AZ 85282
1. Meyer TJ, Hill NS. Noninvasive positive pressure ventilation to treat
respiratory failure. Ann Intern Med. 1994;120:760-70.
2. Biondi JW, Schulman DS, Matthay RA. Effects of mechanical ventilation on right and left ventricular function. Clin Chest Med. 1988;9:5571.
3. Sternberg R, Sahebjami H. Hemodynamic and oxygen transport characteristics of common ventilatory modes. Chest. 1994;105:1798-803.
4. Confalonieri M, Gandola L, Aiolfi S, Scartabellati A, Delia Porta R.
Prognostic factors for success/failure of noninvasive pressure support
ventilation in severe exacerbations of COPD [Abstract]. Am J Respir
Crit Care Med. 1994; 149:A639.
5. Bone RC. Acute or chronic respiratory failure. JAMA. 1989;261:344453.
In response: Confalonieri and colleagues raise the issue of
appropriate selection guidelines for the use of noninvasive positive pressure ventilation in patients with acute respiratory failure.
They correctly point out that "hemodynamic instability" was not
precisely defined in our review, and they report their experience
with a series of patients, including some with hypotension, most
of whom were successfully treated with noninvasive positive pressure ventilation. Information on the appropriate use of noninvasive positive pressure ventilation in patients with acute respiratory failure is evolving, and it is not possible to delineate precise
patient selection criteria because of the lack of well-designed
scientific studies in the literature. The selection guidelines that
we presented in our article were culled from currently available
studies and our own experience, but it is important to emphasize
that they are only guidelines and that clinical judgment must
always be exercised when they are applied in individual patients.
Confalonieri and colleagues also failed to precisely define hemodynamic instability, and their definition of hypotension (systolic blood pressure <100 mm Hg) is fairly lenient. We agree
that the patients described by Confalonieri and associates appear
to have been appropriately selected as candidates for noninvasive
1. Garcia PJ, Schein RM, Burnett JW. Fulminant hepatic failure from sea
anemone sting. Ann Intern Med. 1994;120:665-6.
In response: We initially considered the possibility of a bacterial infection with Vibrio. Multiple blood cultures and a skin
culture were negative. In addition, this patient's presentation was
not consistent with V vulnificus infection, which has been associated with three very different clinical syndromes: primary septicemia, wound infections, and gastrointestinal illness without
septicemia or wound infection (1). Patients with primary septicemia have a preexisting liver disease, and some have reported a
recent history of consuming raw oysters. Patients with wound
infections often have fever, pain and swelling at the wound site,
and cellulitis. In a study of the clinical and epidemiologic features of V. vulnificus infections in Florida from 1981 to 1987, V
vulnificus was cultured from the wound site alone in 8 of 17
patients with wound infections and from skin lesions or blood in
the rest. Of the four patients who died, all had blood cultures
positive for V. vulnificus, and all had underlying chronic diseases.
None of the 11 patients without chronic diseases died. Rapid
extension of the cellulitis and swelling in the same extremity as
the wound was seen.
Our patient was a healthy young man with no underlying
illness. Dexamethasone was started in his second visit to the
hospital. At that time, 24 hours after the sting, he was already
encephalopathic. Blood and wound cultures were all negative,
and no evidence of cellulitis or inflammation was noted surrounding the lesion. Liver study findings did not suggest ischemic
liver injury.
A lower IgG titer is more consistent with previous exposure.
Although it would have been preferable to measure IgM, the
technique for this is not available. Because the titers were high
and were from the same species recognized as the offender, we
feel that the serologic results indicate acute envenomation.
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Patricia J. Garcia, MD
University of Washington
Seattle, WA 98122
Roland M. H. Schein, MD
Veterans Affairs Medical Center
Miami, FL 33125
Joseph W. Burnett, MD
University of Maryland School of Medicine
Baltimore, MD 21201
1. Klontz K, Spencer L, Schreiber M, Janowski HT, Baldy LM, Gunn RA.
Syndromes of Vibrio vulnificus infections. Clinical and epidemiologic
features in Florida cases, 1981-1987. Ann Intern Med. 1988;109:318-23.
Methamphetamine-induced Choreoathetosis and
To the Editor: Illicit use of a crystalized, smokable form of
methamphetamine ("ice") has markedly increased (1). Small
doses can produce significant central nervous system, cardiovascular, and systemic toxic effects. We describe a previously healthy
man who developed choreoathetosis and rhabdomyolysis after
using crystalized methamphetamine.
A 50-year-old man presented to an inner-city hospital in metropolitan Atlanta reporting a 2-day history of hiccups and uncontrollable writhing movements of his face and hands. He had
not previously experienced any similar symptoms. He denied any
family history of movement disorders, ethanol or substance
abuse, intake of medications, or previous illnesses. He was employed as an insect exterminator and had not recently changed
any of the chemicals with which he worked. In fact, he had been
on vacation from his job for the previous week.
Physical examination showed a hypomanic affect and noticeable choreiform movements of the upper extremities, head, and
neck. His temperature was 38 °C, and orthostatic changes were
evident. Dry mucous membranes and flat neck veins were noted.
He was alert and oriented but also hyperverbal, with loose associations, tangential thoughts, and a decreased attention span.
Laboratory values included a sodium level of 119 mEq/L, a
potassium level of 2.9 mEq/L, a chlorine level of 62 mEq/L, a
bicarbonate level of 34 mEq/L, a blood urea nitrogen level of 63
mg/dL, a creatinine level of 6.0 mg/dL, a phosphorus level of 6.3
mmol/L, a serum glutamic-oxaloacetic transaminase level of 177
IU/L, and a uric acid level of 9.7 mg/dL. Examination of roomair blood gases showed a P02 of 65 mm Hg, a PC02 of 40 mm
Hg, and a pH of 7.61. Urinalysis showed a pH of 8.0 and blood
positivity by dipstick, but no erythrocytes were seen on microscopic evaluation. His electrocardiogram was remarkable only for
a prolonged QT interval. Additional laboratory studies were significant for a creatine kinase level of 7664 IU/L, which peaked at
19 790 IU/L, and a lactate dehydrogenase level of 491 IU/L.
Serum lithium level; ceruloplasmin, ammonia, and thyroid function test results; rheumatoid factor; antinuclear antibodies; and
antistreptolysin-O titers were all negative or within normal limits.
Extensive drug toxicology screens were positive only for amphetamines.
Treatment included vigorous hydration with normal saline.
During a 7-day hospitalization, the choreiform movements, electrolyte abnormalities, and creatine kinase levels gradually returned to normal. On hospital day 6, the patient's girlfriend
brought in a packet containing a white crystalline substance,
which the patient refused to specifically identify. He admitted,
however, that he believed the substance caused his condition.
The substance was analyzed in the toxicology laboratory and was
determined to be methamphetamine.
Rhee and colleagues (2) reported three cases of acute choreoathetosis associated with amphetamine-like drugs. In addition, a
few cases of rhabdomyolysis related to methamphetamine have
been documented (3). A single case of choreoathetosis and rhabdomyolysis related to pemoline, a sympathomimetic agent similar
to amphetamine and ritalin, was reported in 1988 (4).
In our patient, the choreoathetosis was probably related to the
central dopaminergic effects of methamphetamine (5), as was the
patient's mildly psychotic and agitated behavior. Rhabdomyolysis
was most likely a result of the drug itself, possibly in combination
with the excessive, uncontrollable muscular activity of chorea.
The severe metabolic derangements were probably the result of
significant dehydration following an "amphetamine run," rhabdomyolysis, and the alkaline property of amphetamines.
Laurence S. Sperling, MD
Emory University School of Medicine
Atlanta, GA 30322
Jennifer L. Horowitz, MD
University of Washington
Seattle, WA 98195
1. Derlet RW, Heischober B. Methamphetamine—stimulant of the 1990s?
West J Med. 1990;153:625-8.
2. Rhee KJ, Albertson TE, Douglas JC. Choreoathetoid disorder associated with amphetamine-like drugs. Am J Emerg Med. 1988;6:131-3.
3. Chan P, Chen JH, Lee MH, Deng JF. Fatal and nonfatal methamphetamine intoxication in the intensive care unit. J Toxicol Clin Toxicol.
4. Briscoe JG, Curry SC, Gerkin RD, Ruiz RR. Pemoline-induced choreoathetosis and rhabdomyolysis. Med Toxicol Adverse Drug Exp. 1988;
5. Kanazawa I, Kimura M, Murata M, Tanalca Y, Cho F. Choreic movements in the macaque monkey induced by kainic acid lesions of the
striatum combined with L-dopa. Pharmacological, biochemical, and
physiological studies on neural mechanisms. Brain. 1990;113:509-35.
Blueberry Muffins and Mystery Novels
To the Editor: I am saddened and embarrassed to have read
Dr. Linzer's essay "Blueberry Muffins and Mystery Novels" (1).
The type of experience described and the relationship established
with the patient is something that those of us who practice
medicine 12 months of every year share on a daily basis. Relating
to our patients in a personal manner without "detached concern
that is supposed to define our relationships with patients" is
something that we should do most of the time. It should not be
something so unusual as to be considered "crossing over the
How unfortunate for the medical student who told Dr. Linzer
that "this was one of the most powerful experiences he had had
in medical school," when it should be a fairly common one. For
many thousands of physicians it is, was, and always will be part
of being a doctor.
William Burns, MD
West Allis, WI 53227
1. Linzer M. Blueberry muffins and mystery novels. Ann Intern Med.
In response: If only we all had the opportunity to establish
long-lasting and meaningful relationships with patients on a daily
basis! Certainly, few patients today would say that their physicians connect with them, explain things clearly, and take the time
to get to know them. As Co-Chair of the Society of General
Internal Medicine's Task Force on Career Choice, I have spent
years asking medical students why they are no longer interested
in careers in internal medicine (1, 2). The reason given most
often is an inability to establish meaningful relationships with
patients during medical training. The students ask us to increase
outpatient exposure to correct this problem.
Thus, Dr. Burns' perception may depend on location. The
outpatient-based physician will usually connect with his or her
patients over the years. However, I remember when I was a
medical house officer and would work all night to restore a
desperately ill patient to health. In the morning, the private
physician would walk in and the patient would glow at his doctor
and say how happy he was to see him. I would feel left out of
that "connexional" (3) energy.
The in-hospital training environment is toxic to good relationships. Patients enter desperately ill and leave after a diagnostic-
15 December 1994 • Annals of Internal Medicine • Volume 121 • Number 12
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related group-determined, foreshortened length of stay, long
before a house officer, student, or attending physician can establish a relationship with them. Being the "attending of the month"
on the wards (as I was with Mrs. Tyler) leaves one particularly
vulnerable to this situation. To recapture students' (and perhaps
our own) interest in internal medicine, we will need to either
alter this environment or put students in physicians' offices,
where they can see patients in a longitudinal manner and establish the relationships craved by those of us who chose internal
medicine (4).
I agree that it was "unfortunate" for my student that this
should have been one of his most "powerful experiences during
medical school." But it was, and we must not let that remain the
case. Courses such as the one run by Dr. Mack Lipkin at New
York University (eloquently described in Anna Quindlen's recent
New York Times article [5]) will help many of us learn how to
restore medicine to the personally connected profession described by Dr. Burns. Because many physicians fear that health
reform, with its emphasis on managed care and "business-like
medicine," will further endanger the doctor-patient relationship,
we must insist that this relationship be the core of medical
practice and that sufficient time in the office and at the bedside
must be allowed for it to flourish.
reer Choice in Internal Medicine. Medical student interest in internal
medicine. Ann Intern Med. 1991;114:6-15.
McMurray JE, Schwartz MD, Genero NP, Linzer M, for the Society of
General Internal Medicine Task Force on Career Choice in Internal
Medicine. The attractiveness of internal medicine: a qualitative analysis
of the experiences of female and male medical students. Ann Intern
Med. 1993;119:812-8.
Matthews DA, Suchman AL, Branch WT Jr. Making "connexions":
enhancing the therapeutic potential of patient-clinician relationships.
Ann Intern Med. 1993;118:973-7.
Lewis CE, Prout DM, Chalmers EP, Leake B. How satisfying is the
practice of internal medicine? Ann Intern Med. 1994;114:1-5.
Quindlen A. The human touch. New York Times. 14 May 1994.
Correction: Author in Reference
To the Editor: A reference in a recent editorial (1) contained a
misspelled author name. The first author of reference 6 should
be "Balestra."
1. Task Force on Adult Immunizations. Adult Immunizations 1994. Ann
Intern Med. 1994;121:540-1.
Correction: Price of Book
Mark Linzer, MD
University of Wisconsin-Madison
Madison, WI 53792
1. Schwartz MD, Linzer M, Babbott D, Divine GW, Broadhead E, and the
Society of General Internal Medicine (SGIM) Interest Group on Ca-
To the Editor: The price of a recently listed book was incorrect.
The price of Could It Be HIV?: The Clinical Recognition of HIV
Infection is $20.00. A second edition of this book has been
published and can be obtained from the publisher: Australian
Medical Publishing Company, 76 Berry Street, North Sydney,
NSW 2059, Australia.
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Thanks to Reviewers—1994
The strength of Annals depends in large measure on the ability and efforts of many hundreds of reviewers. Below, we
have listed the consultants who reviewed between 1 November 1993 and 31 October 1994. They have provided a service—for editors, to be sure—but also for authors, readers, and the medical community as a whole.
Richard Aach
Joseph A Abbott
Nabih I Abdou
Walter H Abelmann
Janet Abrahm
Donald I Abrams
Fredrick R Abrams
Edgar Achkar
James L Achord
John S Adams
Patricia Adams
Harold P Adams Jr
Philip A Ades
Alan G Adler
Nanakram Agarwal
David P Agle
Vincent Agnello
Naurang M Agrawal
David A Ahlquist
Yeon S Ahn
Robert K Ahrens
Judith Ahronheim
Alan C Aisenberg
Jaffer A Ajani
Graciela S Alarcon
Abass Alavi
Boris Albini
Margaret J Albrink
Valiere Alcena
Cathy A Alessi
Raymond Alexanian
Cesar Alfonso
Allen C Alfrey
David Alland
John P Allegrante
Robert F Allnutt
Joseph S Alpert
Martin A Alpert
Milton Alter
Lawrence K Altman
Roy D Altman
Murray D Altose
Barbara Alving
Michael J Aminoff
Arthur J Ammann
Neil M Ampel
James W Anderson
Odin W Anderson
George Annas
Jack E Ansell
Frederick R Appelbaum
Peter C Appelbaum
Gary B Applebaum
William B Applegate
Nicolas Argy
James O Armitage
Donald Armstrong
Robert Arnold
Paul M Arnow
Wilbert S Aronow
Kristan Aronson
Mark Aronson
Ann M Arvin
Arthur K Asbury
David Atkins
Anne-Marie Audet
Robert C Austrian
Daniel L Azarnoff
Charles F Babbs
Richard Bach
Bruce R Bacon
Larry M Baddour
Maria R Baer
Geetha Baht
John Baillie
Cornelia Baines
C Noel Bairey
Alfred L Baker
Daniel Baker
George L Bakris
Louis Balart
Lodovico Balducci
John A Balint
James E Balow
Albert Balows
Simmy Bank
Peter Banks
John Banwell
Emil J Bardana Jr
Peter Barland
Peter Barnes
Jeremiah A Barondess
A Sidney Barritt III
John G Bartlett
David R Bassett
Joseph H Bates
Renaldo Battista
Douglas C Bauer
Kenneth A Bauer
Conrad Bauknight
Kay Bauman
William G Baxt
John D Baxter
Ahmet Baydur
Gildon N Beall
J Robert Beck
John C Beck
Laurence H Beck
Charles E Becker
Mark H Beers
Paul Beeson
Benjamin Befeler
Gregory J Beirne
David Bell
Malcolm Bell
William R Bell
George A Beller
Robert B Belshe
Jorge L Benach
Harold Z Bencowitz
Earl P Benditt
Joel Bennett
John M Bennett
William M Bennett
Neal L Benowitz
Gordon D Benson
D Woodrow Benson Jr
Eugene S Bereston
Robert G Berger
Timothy G Berger
Lars Berglund
Steven L Berk
Jesse A Berlin
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Daniel Berlowitz
Geoffrey M Berlyne
James L Bernat
James Bernene
Harold Bernstein
Joel I Bernstein
Steven Bernstein
Jack Berryman
Alice N Bessman
Joel Betesh
Robert F Betts
Gietha Bhat
Jesus Bianco
Philip Bierman
Diane E Bild
Roger A Billhardt
John E Billi
Henry J Binder
Peter F Binnion
Shawn J Bird
Margaret D Bischel
Alan L Bisno
Neville Bittar
Henry R Black
Henry W Blackburn Jr
Neil R Blacklow
Donald C Blair
Christina G Blanchard
John H Bland
Andres T Blei
Mark J Bliton
E Richard Blonsky
Bernard S Bloom
Charles D Bluestone
Manfred Blum
Bruce D Blumberg
David Blumenthal
William B Blythe
Guenther Boden
William Boden
Monty M Bodenheimer
Morton D Bogdonoff
Eugene Boisaubin
John K Boitnott
Kline W Bolton
John Bomalaski
Roger C Bone
Michael Bongiovanni
Herbert Bonkovsky
Ernest C Borden
Donald R Bordley
Donald L Bornstein
Edward J Bottone
Edmund Bourke
Randall Bovbjerg
Alfred Bove
Raleigh Bowden
James M Boyle
Eugene M Bozymski
Samuel Bozzette
Phillip Brachman
Gregory L Braden
Roscoe O Brady
Hayden G Braine
S Philip Bralow
William T Branch
Richard F Branda
Lawrence F Brass
Norma M Braun
Glenn D Braunstein
Emmanuel L Bravo
Warren Breisblatt
Troyen Brennan
Joseph S Bresee
Donald Breslin
Julia A Breyer
Philip W Brickner
C D Brock
Martin I Broder
Gregory Broderick
Jerome I Brody
David L Bronson
Robert H Brook
Benjamin R Brooks
David Brown
Kenneth A Brown
Robert S Brown
Theodore M Brown
Sheldon Brownstein
Nadine Bruce
Louis L Brunetti
Frank J Bruns
John C Brust
R N Bryan
Richard E Bryant
James W Buehler
Paul A Bunn Jr
Howard Burchell
Kathryn L Burgio
Donald S Burke
James Burke
Wylie Burke
Gerard N Burrow
Alan Burshell
Benjamin T Burton
Trudy Bush
Donald E Butkus
Joel N Buxbaum
Timothy Byers
Benjamin F Byrd III
John J Byrnes
Richard L Byyny
Fernando Cabanillas
John Cairns
Robert Califf
Evan Calkins
Hugh Calkins
Gregory Call
Christopher Callahan
David J Callans
C Wayne Callaway
Jeffrey P Callen
Michael Camilleri
Richard C Cammerer
James Campbell
John J Canary
Louis R Caplan
George J Caranasos
Robert M Carey
Timothy Carey
William D Carey
Robert L Carithers Jr
Charles C Carpenter
Paul C Carpenter
David T Carr
S George Carruthers
James R Carter Jr
Angelina C Carvalho
Carl E Cassidy
Donald O Castell
William P Castelli
Lon Castle
Kenneth G Castro
Marc Catalano
James F Cawley
John Cello
Robert M Centor
James J Cerda
James R Cerhan
James M Cerletty
Richard E Chaisson
Bernard Chaitman
Thomas C Chalmers
Henry Chambers
Richard A Chambers
Richard Champlin
Arlene Chapman
John S Chapman
N David Charkes
Stephen Chavin
Joseph A Chazan
Tsung O Cheng
Bart Chernow
Elliot Chesler
Bruce D Cheson
William Y Chey
Joan S Chmiel
Gerald W Chodak
Sunwen Chou
Te-Chaun Chou
Michael J Chusid
David J Clain
Carolyn M Clancy
David Clive
Christopher Clyne
Jack W Coburn
Cecil H Coggins
Harvey J Cohen
Jules Cohen
Marc Cohen
Martin H Cohen
Myron S Cohen
Philip Cohen
David L Cohn
Graham A Colditz
Karan Cole
Monroe Cole
Randolph P Cole
Jack M Colford
Elaine Collier
Theodore Colton
David S Colville
Philip C Comp
George W Comstock
Marcus A Conant
Hadley L Conn Jr
Julia E Connelly
Allan R Cooke
Leo Cooney
David S Cooper
Constantin Cope
Dennis W Cope
John B Copley
Eugene C Corbett Jr
Clinton N Corder
Lawrence Corey
Deborah J Cotton
Richard S Crampton
Donald E Craven
Robert Crawford
Stephen W Crawford
Ralph Crawshaw
Mark Creager
Louis L Cregler
Rose Cristopherson
Carlo M Croce
Carol Cronin
Alan Cross
Kent B Crossley
Mark R Cullen
Steven R Cummings
Charlotte Cunningham-Rundles
Thomas R Cupps
James W Curran
William L Current
Edward I Curtiss
Ralph E Cutler
Giulio D'Angio
Gail Dalsky
Marion Danis
Gabriel M Danovitch
David R Dantzker
Raymond J Dattwyler
William H Daughaday
W Dale Dauphinee
Frank Davidoff
Bruce Davidson
Mayer B Davidson
Gary L Davis
John S Davis
Paul J Davis
Stephen Davis
Susan Day
Michael De Buitler
Piet C De Groen
Raphael J De Horatius
Joseph M Delehanty
Tom R Demeester
Mark Demitrack
Herman C Denber
Margo Denke
Charles W Denko
Susan Denman
Floyd W Denny
Vincent L Dequattro
Richard A Deremee
Julius J Deren
Norman Desbiens
Chris Desch
Kenneth B Desser
Allan S Detsky
Susan Deutsch
Richard B Devereux
John Devlin
Daniel Deykin
George A Diamond
Herbert S Diamond
Kay Dickersin
Evelyn R Dienst
Robert O Dillman
James C Dillon
Eugene P Dimagno
Mark Dinubile
John H Dirckx
William E Dismukes
Roy Ditchey
James E Doherty
John Doherty
James G Dolan
Raphael Dolin
Donald C Doll
Robert M Donaldson Jr
Charles D Donohoe
Sam T Donta
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Cornelius P Dooley
Joseph T Doyle
Caroline Dressier
Douglas A Drossman
George Drusano
David J Drutz
Satya D Dubey
Joseph Duffy
George Dunea
W Bruce Dunkman
Herbert L Dupont
Janice P Dutcher
Roger C Duvoisin
Harvey J Dworken
Robert H Earhart
David Earnest
J Donald Easton
Charles B Eaton
Debra S Echt
Mark Eckman
Michael Econs
Paul H Edelstein
Howard A Eder
John Edwards
Mark B Effron
Richard L Ehrenberg
George E Ehrlich
Theodore C Eickhoff
Thomas R Einarson
Robert A Eisenberg
Baroukh E El Kodsi
Michael Eliastam
George M Eliopoulos
Kenneth Ellenbogen
Peter Ellis
Joann G Elmore
Rebecca Elon
Arthur S Elstein
Ezekiel Emmanuel
Nicholas Emmanuel
Toby R Engel
Sol Epstein
William L Epstein
Charles D Ericsson
Max Essex
J Worth Estes
N A Mark Estes III
Bruce Ettinger
Arthur Evans
C Edward Evans
Daniel E Everitt
John L Fahey
Thomas J Fahey Jr
Rodney H Falk
Harold J Fallon
Neil J Farber
Barry Farr
Homayoon Farzedegan
Martin Favero
Henry M Feder Jr
Daniel Federman
Alan M Fein
Arthur W Feinberg
Lawrence E Feinberg
Saya V Feinman
Alvin Feinstein
Frederick Feit
Robert Fekety
Ronald Feld
Mark Feldman
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Roy S Feldman
David T Felson
Gladys Fenichel
Bradley W Fenton
Robert P Ferguson
Victor Ferrari
W Jeffrey Fessel
Marshal P Fichman
Carl J Fichtenbaum
Stanley B Fiel
Howard Fillit
S Edwin Fineberg
Sydney M Finegold
Wayne H Finley
Thomas E Finucane
Gary Firestein
Margaret A Fischl
George Fisher
Mary S Fisher
Rosemarie L Fisher
Faith T Fitzgerald
Mary Flack
David Fleischer
Mary Ann Fletcher
Robert H Fletcher
Suzanne W Fletcher
William P Follansbee
Ignatius W Fong
Kenneth A Foon
Mary Ann Forciea
Amasa B Ford
Daniel E Ford
Marvin Forland
Lachlan Forrow
Nicholas J Fortuin
Francine Foss
Malcolm Foster
Jackson E Fowler
Noble O Fowler
Arthur C Fox
Daniel M Fox
Kathleen Fox
Renee C Fox
Henry Fraimow
Gary S Francis
Ian Frank
Victoria Fraser
Howard S Frazier
Donald S Fredrickson
James W Freston
Gerald Friedland
Eli A Friedman
Howard Friedman
Lawrence S Friedman
Peter L Friedman
Scott L Friedman
James F Fries
Mary Frishman
Victor F Froelicher
Edward D Frohlich
Jiri Frohlich
Harold Frucht
Howard Frumkin
Mark G Fuller
Daniel Furst
Eugene D Furth
Palmer H Futcher
Thomas G Gabuzda
Thomas R Gadacz
Robert P Gale
John Galgiani
James P Ganley
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Nelson M Gantz
Hasan Garan
Alan M Garber
Harinder S Garewal
Richard Garibaldi
Stephen Gebarski
Timothy S Gee
Michael A Geheb
H Jack Geiger
Lawrence Geiter
Robert B Geller
Edward M Geltman
Harry K Genant
F John Gennari
Michael Gent
Edward Genton
Paul D Gerber
Dale N Gerding
Martha S Gerrity
Bernard J Gersh
Stanton L Gerson
Merril Gersten
Gary Gerstenblith
Neil Gesundheit
Thomas E Getzen
Hossein Gharib
Cameron N Ghent
Mihai Gheorghiade
Alexandra Gibas
Raymond Gibbons
Allan Gibofsky
Ray W Gifford Jr
Barbara A Gilchrest
Donald Gilden
Thomas M Gill
Richard F Gillum
Roger D Gingrich
Allen L Ginsberg
Gregory G Ginsberg
Jeffrey S Ginsberg
Jack A Ginsburg
Eli Ginzberg
Harold M Ginzburg
Ellen M Ginzler
Donald E Girard
Norman Gitlin
Stanley Gitlow
Michelle Glasgow
Jeffrey Glassroth
Richard Gleckman
William P Glezen
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James J Goedert
Vivek Goel
Jonathan W Gold
Martin Goldberg
Rochelle Goldberg
Stanley Goldfarb
Norbert Goldfield
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Elliot Goldstein
Sidney Goldstein
Ellen H Golodner
Stasha Gominak
Henry H Gong Jr
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Scott Goodnight
James Goodrich
John Goodson
James S Goodwin
Fred Gordin
Gary V Gordon
Philip B Gorelick
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Barbara Gothe
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Jonathan E Gottlieb
Michael S Gottlieb
Ronald Gottlieb
Lawrence A Gould
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Edward J Gracely
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Richard W Gray
Frank A Greco
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Bernard R Greenberg
Henry Greenberg
Mark Greenberg
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Norton J Greenberger
Paul A Greenberger
H Leon Greene
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M Andrew Greganti
Michael R Grey
David Grob
Jeffrey Groeger
Jay N Gross
Peter Gross
Joshua B Grossman
Robert A Grossman
Robert Gruninger
Richard L Guerrant
Harry A Guess
Subhash C Gulati
Jerry H Gurwitz
David W Haas
John G Haddad Jr
Nortin M Hadler
Bevra H Hahn
John D Hainsworth
Wayne A Hale
Amir Halevy
Robert W Haley
Thomas J Haley
William J Hall
Aaron Hamb
John Hamilton
Robert W Hamilton
Sherrell L Hammar
Bruce H Hamory
Stephen B Hanauer
Roger Hand
Kenneth R Hande
Ruth S Hanft
Joseph P Hanna
John Hansen-Flaschen
William G Hardison
Denham Harman
John W Harmon
J Kevin Harrison
Marilyn T Haupt
Stephen Havas
Richard J Havel
R Brian Haynes
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Julian Haywood
William R Hazzard
Louis A Healey Jr
Robert P Heaney
Hunter Heath HI
Clark W Heath Jr
Lee A Hebert
Paul S Heckerling
John Heit
Marc Hellerstein
Fred J Hellinger
David K Henderson
J Michael Henderson
Thomas R Hendrix
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Charles H Hennekens
David H Henry
Peter Herbert
Victor D Herbert
Irving Herling
Dorothee Herlyn
Carla Herman
William H Herman
Howard Herrmann
William Hersh
Linda A Hershey
Noel B Hershfield
Barry C Herzlich
Steven P Heyse
David H Hickam
Michael Higginbotham
Kevin P High
Maurice Hilleman
Bruce E Hillner
Eileen Hilton
Jules Hirsch
Shalom Z Hirschman
John W Hirshfeld Jr
Marc C Hochberg
Marion E Hodes
Glenn R Hodges
Morrison Hodges
John C Hoefs
Gary Hoffman
Phillip E Hoffsten
Mary T Hofmann
Angela R Holder
Paul V Holland
Stephen K Holland
Daniel Hollander
Harry Hollander
J William Hollingsworth
Jay Hollman
Timothy J Holzer
Howard D Homesley
W K Hong
William B Hood Jr
Jay H Hoofnagle
Philip L Hooper
Sandra J Horning
Richard Horton
David L Horwitz
Daniel F Hoth
Joel Howell
Donald E Hricik
James M Hughes
Walter T Hughes Jr
Gene G Hunder
Gary W Hunninghake
Tim B Hunter
Aryeh Hurwitz
Jodie Hurwitz
Florence N Hutchison
Richard W Hyde
Lisa Iezzoni
Thomas F Imperiale
Tsuyoski Inoshita
Deborah L Isaac
Michael D Iseman
Abdulmassih S Iskandrian
William L Isley
Eloy Ituarte
Diane G Ives
Joseph A Jacobs
David Jacobs Jr
George A Jacoby Jr
Allan S Jaffe
Elaine Jaffe
Harold W Jaffe
Edward N Janoff
Roger W Jelliffe
Anthony S Jennings
J Richard Jennings
John Jennings
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Norman M Jensen
Robert T Jensen
James R Jett
Raphael Jewelewicz
Susan Jick
David R Jobes
Carol J Johns
Bruce E Johnson
David H Johnson
James R Johnson
Paula Johnson
C Conrad Johnston Jr
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M Colin Jordan
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Amy Justice
Lawrence J Kagen
James Kahn
Sigmund B Kahn
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Lawrence Kaiser
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Robert L Kane
Rosalie Kane
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William B Kannel
Norman M Kaplan
Wishwa Kapoor
Marshall B Kapp
Adolf W Karchmer
Judith E Karp
Simon Karpatkin
Michael Karpf
Jacob Karsh
David T Karzon
Carlos S Kase
Sidika Kasim
Richard A Kaslow
Barry Katz
Leonard A Katz
Paul Katz
Carol Kauffman
Arnold F Kaufmann
Sanjiv Kaul
Hymie Kavin
Armand Keating
Herbert J Keating
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Harry R Keiser
Mark A Kelley
Gerald J Kelliher
John G Kelton
Donald J Kennedy
Donald C Kern
Kenneth Kessler
Muhammad A Khan
Sundeep Khosla
Douglas P Kiel
Charles Kilo
Harry Kimball
Michael B Kimmey
Gary T Kinasewitz
Bruce Kinosian
M A Kirschner
Jay W Kislak
Abbas E Kitabchi
Carl M Kjellstrand
Michael J Klag
Lynell W Klassen
Charles R Kleeman
Michael Kleerekoper
George J Klein
Irwin Klein
Joel D Klein
Robert S Klein
David L Kleinberg
Anne Klibanski
Lewis Kline
John H Klippel
Albert B Knapp
William A Knaus
Sidney Kobrin
Scott Koenig
Raymond S Koff
Daniel M Kolansky
Marin H Kollef
Anthony L Komaroff
George T Kondos
Marvin A Konstam
Stanley G Korenman
Ronald L Koretz
Joseph Korn
Morris N Kotler
Robert M Kotloff
Thomas Kottke
Joseph A Kovacs
Murray Krahn
Lawrence R Krakoff
Barnett S Kramer
Mark S Kramer
Robert J Kramer
Edward L Krawitt
Robert A Kreisberg
Harvey Kreisman
Joel Kremer
Benjamin Krevsky
Lloyd M Krieger
Nancy Krieger
Kurt Kroenke
Itzhak Kronzon
Michael J Krowka
Susan E Krown
Harlan M Krumholz
Spencer Kubo
David J Kudzma
Friedrich Kueppers
Donald H Kuiper
Prem Kumar
Peter T Kuo
Daniel Kuritzkes
John F Kurtzke
Robert Kushner
Steven Kutalek
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K J Kwon-Chung
Robert A Kyle
John La Puma
Andras G Lacko
Michael A LaCombe
F Marc Laforce
Robert Lahita
Kwan K Lai
Loren Laine
Carol L Lake
Stanford I Lamberg
Charles Lambert
John S Lambert
Richard L Landau
C Seth Landefeld
Sheldon A Landesman
Philip J Landrigan
H Clifford Lane
Timothy W Lane
Patricia Langenberg
Paul N Lanken
Lars C Larsen
David W Larson
Eric B Larson
Richard Larson
Louis C Lasagna
Bret A Lashner
Robert J Laskowski
Paul R Latimer
Mark Laughlin
Jeffrey Laurence
Ian R Lawson
William J Lawton
Hillard M Lazarus
Thierry H Le Jemtel
Michael D Lebowitz
Dennis K Ledford
Melinda Lee
Robert E Lee
Thomas H Lee
William M Lee
John M Leedom
Glen A Lehman
Michael Lehmann
Jacob Lemann Jr
Louis Lemberg
Martha L Lepow
A Martin Lerner
Barron H Lerner
Jon Levenson
Gerald S Levey
Bernard Levin
Richard Levin
Gary M Levine
Joel B Levine
Mark A Levine
Myron M Levine
Robert A Levine
Shirley Levine
Stephen B Levine
Daniel Levinson
Joseph E Levinson
Wendy Levinson
William Levis
Michael H Levy
Charles E Lewis
David Lewis
H Daniel Lewis
15 December 1994 • Annals of Internal Medicine • Volume 121 • Number 12
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Jon Lewis
Robert B Lewis
Daniel M Libby
Angelo Licata
Charles W Lidz
Jauw-Tjen Lie
Robert W Lightfoot Jr
Stuart L Linas
Robert Lindsay
Mark Linzer
Mack Lipkin Jr
Marvin M Lipman
Robert Lisak
Donald Liss
Lawrence Litt
Bernard Lo
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W Thomas London
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Floyd Loop
Joseph Loscalzo
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Donald B Louria
John M Luce
Jerry C Luck
Phillip Ludbrook
Kenneth M Ludmerer
Edward K Lufkin
Sheila A Lukehart
Barbara P Lukert
Keith Lurie
Nicole Lurie
Larry Lutwick
Richard G Lynch
John MacDonald
Rob Roy MacGregor
Roger Macklis
Philip Mackowiak
Scott L Mader
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Ahazem Mahmoud
Michael H Malim
Martin M Mandel
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Denis Mangano
Robert Marcus
Mitchell Margolis
Daniel B Mark
Avi B Markowitz
Harry Marks
Leona E Markson
Christina Marra
Henry J L Marriott
Julian B Marsh
Paul Martin
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Edward Mascioli
Bernard Mason
Robert M Massanari
Barry Massie
Henry Masur
William Matthai
Michael A Matthay
Dale Matthews
Robert Matz
William Maule
Russell C Maulitz
Chester J Maxson
Douglas R Maxwell
Robert J Mayer
Ernest L Mazzaferri
Denis M McCarthy
Joseph McClellan
William M McConahey
Keith McCrae
Joseph E McDade
John C McDonald
Frederic C McDuffie
William C McGaghie
Thomas McGarrity
Douglas B McGill
Katherine A McGlynn
William P McGuire
Kelly T McKee
K Ann McKibbon
Victor McKusick
James P McManus
Kenneth E McMartin
Julia E McMurray
Jawahar L Mehta
Diane E Meier
Wayne Meikle
Curtis L Meinert
Steven G Meister
James C Melby
Mark Mellow
Shlomo Melmed
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Franz H Messerli
Esteban Mezey
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Steven H Miles
Anthony Miller
Bess Miller
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Wallace Miller
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Richard A Mintzer
Robert I Misbin
Mack C Mitchell
Ronald Mitsuyasu
Pramod K Mohanty
David Mohr
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Joan Mollman
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Richard D Moore
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Lincoln Moses
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Patrick Mulrow
Gregory R Mundy
Robert Munford
Robert L Murphy
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Sucha Nand
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David T Nash
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C David Naylor
Samuel W Needleman
Jerald C Nelson
Kenneth E Nelson
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Georgia L Newman
Tu Nguyen
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Stephen S Nightingale
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James Nolan
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John J Norcini
Joe R Norman
Donald W Northfelt
Sherwin B Nuland
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Chester Oddis
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William C Orr
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Jerome Osheroff
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C Kirk Osterland
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Andy Oxman
Robert F Ozols
Alan I Pack
Harold Palevsky
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Robertson Parkman
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Israel Penn
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Marion Peters
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Phillip K Peterson
Mary Petrelli
Michelle Petri
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Sem Phan
Sidney F Phillips
C Glenn Pickard Jr
Claus A Pierach
Warren Piette
Ileana L Pina
John Pinals
Theodore Pincus
C S Pitchimoni
Philip Pizzo
Vance Plumb
Philip J Podrid
Evan Pokorney
Bruce Polsky
Peter Pompei
Roy Poses
Arnold Postlethwaite
James A Poupard
Gail J Povar
William Powderly
Neil Powe
Don W Powell
Melvin R Pratter
Harry G Preuss
Thomas J Preziosi
Harvey D Priesler
Allen Prochazka
Eric N Prystowsky
Reed E Pyeritz
Kenneth Quickel
Thomas C Quinn
G D Qureshi
Linda Rabenek
Peter Rabins
Khether Raby
Justin Radolf
Derek Raghavan
Margaret V Ragni
Daniel W Rahn
Lawrence G Raisz
Jorge Rakela
Louis Rakita
Kenneth H Rand
Eric Raps
Mark Rarick
Robert Ratner
Oscar D Ratnoff
Jean-Pierre Raufman
William Rawlings Jr
15 December 1994 • Annals of Internal Medicine • Volume 121 • Number 12
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Elliot J Rayfield
Gerald Reaven
Paul M Reber
Robert Recker
K Rajender Reddy
Robert Redfield
William Reed
Gayle E Reiber
Nathaniel Reichek
Richard C Reichman
Michael F Rein
Arthur L Reingold
Oscar Reinmuth
Stanley J Reiser
David Relman
Michael Remetz
Jack S Remington
Neil M Resnick
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Herbert Y Reynolds
Vincent M Riccardi
Stuart Rich
Nelson G Richards
Charles T Richardson
David W Richardson
Robert Riddell
Paul M Ridker
Lee B Riechman
Caroline Riely
Richard E Rieselbach
Basil M Rifkind
David J Riley
Charles R Rinaldo
Jack Ringler
Guenter B Risse
George L River
James M Roach
Harold R Roberts
Edward N Robinson
N Wilson Rodger
Arvey I Rogers
Edward C Rosenow III
David S Rosenthal
Mark Rosenthal
Fred Rosner
Douglas S Ross
Philip D Ross
Thomas H Rossing
John C Rowlingson
David J Roy
Frederick L Ruben
Brian G Rubin
Raymond A Rubin
Ronald N Rubin
Stephen C Rubin
Peter Rudd
Richard Rudders
John R Ruddy
Basil Rudusky
George Rutherford
Michael S Saag
Alfred J Saah
Sandra Sabatini
Laura S Sadowski
Charles Safran
Malur R Sairam
Sanjeeb Saksena
Syed Z Salahuddin
Gerald Salen
Jonas Salk
Bonnie Salomon
Gary Salzman
Richard Sampliner
Max Samter
Christine C Sanders
Robert Sandler
David C Sane
Victor Santana
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Fred R Sattler
Paul D Saville
Clark T Sawin
Andrew J Saykin
Angelo M Scano
Stephen F Schaal
Robert Schacht
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Daniel F Schafer
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William Schaffner
Donald S Schalch
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Arnold Schecter
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Jerome H Shapiro
Martin Shapiro
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Albert L Sheffer
Paul Shekelle
Win K Shen
Haynes W Sheppard
Renslow Sherer
Robert J Sheretz
Louis Sherwood
J B Shiroky
Gerald Shklar
15 December 1994 • Annals of Internal Medicine • Volume 121 • Number 12
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David M Shlaes
Bernard R Shochet
Ira Shoulson
Jonas A Shulman
David Siegel
Eugenia L Siegler
Mark Siegler
Leonard H Sigal
Leslie E Silberstein
Edward B Silbertstein
Mark Silverstein
Roy Silverstein
Michael S Simberkoff
Bryan P Simmons
Harold J Simon
Joel Simon
Frederick R Singer
Peter Singer
William Singer
John W Singleton
Ethel Siris
James V Sitzmann
Maria Sjogren
Harry B Skinner
Leonard N Slater
Peter L Slavin
Charles Slemenda
William S Sly
Dale C Smith
David W Smith
J Bruce Smith
Jay W Smith
Leon G Smith
Robert C Smith
Roger P Smith
Nathan M Smulker
Hugh Smythe
James Snell
Michael C Sneller
Gordon L Snider
Charles Snisky
Lois Snyder
David R Snydman
Rosemary Soave
Roy Soeiro
J Stuart Soeldner
Kim Solez
Alan Solomon
Rachel E Solomon
Edmund H Sonnenblick
Michael F Sorrell
Fred Southwick
Robert Spanheimer
George Spencer-Green
Harry Spiera
Sarah Spinier
Thomas J Spira
Gary Spitzer
Roger E Spitzer
Jerry L Spivak
David H Spodick
Spotswood L Spruance
Alagarsamy Srinivasan
Bruce A Staats
Edward Stadtmauer
Lawrence Stanberry
Harold C Standiford
Barbara Starfleld
Mark Starling
William W Stead
Virginia Steen
Allen C Steere Jr
Roy Steigbigel
Evan A Stein
Alfred D Steinberg
William M Steinberg
Richard Steingart
Mark C Steinhoff
Ronald L Stephens
Thomas N Stern
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Rainer F Storb
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Ronald C Strickler
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Harold Szerlip
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Wolf Vogel
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Scott Wadler
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H Gilbert Welch
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Carol Westbrook
Charles V Wetli
Cornelia M Weyand
Carl W White
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Thomas Wise
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Robert Wortmann
Taylor M Wray
Keith D Wrenn
Stephen C Wright
Teresa L Wright
Albert W Wu
David J Wyler
Ernst Wynder
Tadataka Yamada
Robert Yarchoan
Edward Yelin
James M Youakim
James B Young
Jess Young
Lowell S Young
Mark Young
Roy T Young
15 December 1994 • Annals of Internal Medicine • Volume 121 • Number 12
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M Donna Younger
Stuart J Youngner
Victor L Yu
John Zaia
Mohammed H Zarrabi
Darwin Zaske
N Peter Zauber
Jerome B Zeldis
Mark Zervos
15 December 1994 • Annals of Internal Medicine • Volume 121 • Number 12
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Rowen K Zetterman
Wei-Xi Zhu
Samuel Zoneraich
Dorothea Zucker-Franklin
John J Zurlo
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