Open Heart (53 page)

Similarly, stem cells may aid the heart's ability to repair itself. In an article in the
New England Journal of Medicine
, “Chimerism of the Transplanted Heart,” by Federico Quaini et al., 346:1 (January 3, 2002), pages 7–15, researchers report “a high level of cardiac chimerism caused by the migration of primitive cells from the recipient to the grafted heart. Putative stem cells and progenitor cells were identified in control myocardium and in increased numbers in transplanted hearts.” Although “our knowledge of these events is less than scanty,” the
NEJM
reports, these new findings “raise the hope that, counter to traditional beliefs, the heart can repair itself. If it can, we will have opportunities to enhance the process that regenerates damaged myocardium” (page 5).

217
   
“We don't have a splint”:
Although Phil is a man who can understand the most subtle complexities of science—whether physics, biology, chemistry, anatomy, geology, or neuroscience—when it comes to the practice of medicine, and to dealing with his patients, he remains uncomplicated in the best, most sensible ways, so that often, when I become aware of my own tendency to worry a situation too much, I will stop and say to myself: Whoa, Neugie—what would Phil see here, and what would he say? How would he cut through to the heart of this—to the basics?

218
   
Phil has written:
Phil's article, “Bifrontal Brain Trauma and ‘Good Outcome' Personality Changes: Phineas P. Gage Syndrome Updated,” was published in the
Journal of Neurological Rehabilitation
4 (1990), pages 9–16.

218
   
Since my arrival:
“He's genuinely shy,” Phil's wife Barbara says when I talk with her about how hard it is to get Phil to agree to tape a conversation. “And he doesn't always make eye contact either, so sometimes people aren't sure if he's listening. But he is. He's the best listener I know, and he never treats anything—
any
patient—routinely. In the middle of the night I often find he's gotten out of bed and is in his office, poring through his medical books and trying to figure something out about one of his patients.”

226
   
“perceptions of a career”:
Jack Hadley et al., “Young Physicians Most and Least Likely to Have Second Thoughts About a Career in Medicine,”
Academic Medicine
67:3 (March 1992), pages 180–190 [180].

227
   
“The psychic toll”:
Michael D. Burdi and Laurence C. Baker, “Physicians' Perceptions of Autonomy and Satisfaction in California,”
Health Affairs
18:4 (July-August 1999), pages 134–145 [142–143]. See also “Effects of HMO Market Penetration on Physicians' Work Effort and Satisfaction,” by Jack Hadley and Jean M. Mitchell,
Health Affairs
16:6 (November–
December 1997), pages 99–111; “Physician Behavior: Perceived Financial Incentives, HMO Market Penetration, and Physicians' Practice Styles and Satisfaction,” by Jack Hadley et al.,
Health Services Research
34:1 (April 1999, Part II), pages 307–321; and “How Satisfying Is the Practice of Internal Medicine?” by C. E. Lewis et al.,
Annals of Internal Medicine
114 (1991). pages 1–5.

237
   
“There was no arguing”:
On another occasion, after recounting some of Arthur's speculations about our friendships, and about the role of sports in our early lives, I offer a literary comparison: that the schoolyard was for us what the Mississippi was for Mark Twain, and the sea for Melville. I talk about an essay originally published in 1948 by Leslie Fiedler, “Come Back to the Raft Ag'in, Huck Honey!” in which, writing about
Huckleberry Finn
and
Moby Dick
(and other books—all “boy's books,” Fiedler notes) Fiedler proposes that what they have in common is a kind of passionless passion—a homoerotic love between men, at once gross and delicate, and possessing an innocence above suspicion. And this love, and these friendships—the feeling and affection of Huck for Jim, of Ishmael for Queequeg—exist in an American male's version of paradise: a world where men, and only men, work and play together—where they struggle against the elements, rejoice in their camaraderie, and exist in an idyllic, preindustrial American pastoral. “Come Back to the Raft Ag'in, Huck Honey!” in
Adventures of Huckleberry Finn: A Case Study in Critical Controversy
.

243
   
Then he looked up:
The intravenous solution ordered by Dr. Brumlik was digitalis.

243
   
I mention:
Lown, pages xiv and xv.

249
   
According to Koch's postulates:
For a description of these and how he arrived at them, see Roy Porter's
The Greatest Benefit to Mankind: A Medical History of Humanity
, page 436 ff.

250
   
The assumption:
For a discussion of single causative agents in disease—their rarity, and our success rates in finding treatments for them—see Weatherall, page 256 ff, and Victor McKusick, cited in note xx, chapter x.

251
   
Twin studies:
The statistics on concordance rates are from Weatherall, pages 280–281. For an excellent explanation of the relation of genetics to heritability—twin studies, family studies, linkage studies, concordance rates, et cetera—see “Genetic Research on Mental Disorders,” by Stephen O. Moldin, in
Genetics and Criminality
, ed. Botkin, McMahon, and Francis, pages 115–149.

253
   
Evolutionary biologists:
The kinds of questions evolutionary biologists
ask—along with some answers and hypotheses concerning the relationship of disease (cancer and heart disease, in particular) to natural selection—are set forth clearly in Randolph M. Nesse and George C. Williams,
Why We Get Sick: The New Science of Darwinian Medicine
, especially pages 3–6, 96–97, and 134–135

254
   
In a similar way:
For a discussion of the relation of genetics, disease, heritability, and reproductive age, see Nesse and Williams, pages 96–97.
Seen from this perspective:
Richard Dawkins's remark is from Nesse and Williams, page 15.
“natural selection”:
Ewald, page 12.

255
   
“strep B was”:
Laurie Garrett,
The Coming Plague
, page 415. The report on fourteen thousand people dying each year from drug-resistant infections is from an editorial in the
New York Times
, “Losing Ground Against Microbes,” June 18, 2000.

There is a large body of literature concerning the increase in drugresistant infections—for example, an article in the
Archives of Family Medicine
8:1 (January-February 1999), by Jon S. Abramson and Laurence B. Givner (“Bacterial Resistance Due to Antimicrobial Drug Addiction Among Physicians”) noting that

until 1974, all pneumococci reported in the United States were susceptible to penicillins and cephalosporins. Resistance levels increased slowly thereafter until the 1990s, when the rates increased substantially. The US Pediatric Multicenter Pneumococcal Surveillance Study Group prospectively studied almost 1300 systemic infections caused by pneumococci at 8 children's hospitals. They found that from 1993 to 1996, the overall percentage of pneumococci that were penicillin nonsusceptible increased from 14% to 21%. The resistance rate for ceftriaxone tripled, from 3.1% to 9.3%.

Until 1992, the Centers for Disease Control spent only $55,000 a year on antibiotic-resistance surveillance—yet by 1992, as an article in
Science
noted in that year (“On the Track of ‘Killer' TB,” by Rich Weiss),

years of poor compliance among TB patients unwilling to take their medicine for the full 6 to 18 months needed to kill the bugs has led to the gradual development of strains that are now resistant to as many as 9 of the 11 most commonly tested drugs. And although a trend toward drug resistance has been obvious for some time, the severity of the crisis went largely unrecognized in recent years, in part because the federal surveillance programs designed to track TB drug-resistance were eliminated in 1986 for budgetary reasons. (
Science
255:5041 [January 1992], pages 148–150)

Nesse and Williams, pages 1–49 and 246, provide a good introduction to the subject. See also Ewald, pages 1–30. Laurie Garrett's
The Coming Plague
is full of stories and data on drug-resistant diseases.
Richard Preston's writings, especially
The Hot Zone
, and “Annals of Warfare: The Bioweaponeers” (
New Yorker
[March 9, 1998], pages 52–65), provide a primer on the possible uses and effects of lethal drug-resistant viruses.

256
   
None of the risk factors:
For a fascinating discussion of inflammation and its relation to the immune system and heart disease, see Ewald, especially pages 107–116. Joseph B. Muhlestein's quotation is from “Chronic Infection and Coronary Artery Disease,” in Killian Robinson (ed.),
Medical Clinics of North America: Risk Modification for Cardiac Disease
84:1 (January 2000), pages 123–148 [123].

256
   
Moreover, as Lewis Thomas:
For Ewald's discussion of principles of primary causation and their relation to heart disease, see pages 116–121 in
Plague Time
.

257
   
“The entire process”:
For other discussions of the processes that lead from the buildup of atheroma to its rupture, see Dr. Peter Libby, “Atherosclerosis: The New View,”
Scientific American
(May 2002), pages 47–53. See also Klaidman, pages 204–205,199–200,211–215; and Weatherall, pages 94, 280–285.

Dr. Libby, chief of cardiovascular medicine at Brigham and Women's Hospital in Boston, provides a good summary of recent research on the relation of inflammation to cardiovascular disease. The most interesting finding, he suggests, is that “the long held conception of how the disease develops [fat-laden gunk gradually building up on artery walls and closing them off] turns out to be wrong.”

“Most heart attacks and many strokes,” Libby writes, “stem instead from less obtrusive plaques that rupture suddenly, triggering the emergence of a blood clot, or thrombus, that blocks blood flow.” Sometimes, of course, plaque does grow so large that it halts blood flow to an artery, thereby generating a heart attack or stroke, Libby explains. “Yet only about 15 percent of heart attacks happen in this way.”

This “new view” of atherosclerosis helps “explain why many heart attacks seem to come from out of the blue: the plaques that rupture do not necessarily protrude very far into the blood channel and so may not cause angina or appear prominently on images of the channel.” Some plaques, that is, are more prone to rupturing than others, and we really don't know why.

For more detailed discussions of the relation of inflammation to coronary artery disease, see “Inflammation, Aspirin, and the Risk of Cardiovascular Disease in Apparently Healthy Men,” by Paul M. Ridker et al,
NEJM
336:14 (April 3, 1997), pages 973–979; “Measurement of C-Reactive Protein for the Targeting of Statin Therapy in the Primary Prevention of Acute Coronary Events,” by Paul M. Ridker et al.,
NEJM
344:26 (June 28, 2001), pages 1959–1965; and also Weatherall, page 186.

Although the evidence for inflammatory causation is persuasive, the process that produces the ruptures in the atheroma that lead to heart attacks, as Rich often reminds me, remains mysterious. Thus the following, from an editorial article, “The Value of Inflammation for Predicting Unstable Angina,”
NEJM
347:1 (July 4, 2002), pages 55–57: “Although the link between inflammation and clinical cardiovascular events is strong, there remain important gaps in our knowledge. For example, although chronic systemic infection may accelerate the clinical course of atherosclerosis, the relative contribution of this ‘extralesional' inflammation to events within the arterial wall remains to be determined. Similarly, the precise mechanism by which atherosclerosis initiates an inflammatory response is not known” (pages 56–57).

258
   
“Add to this”:
For information on C-reactive protein and its relation to the detection and prevention of atherosclerosis and to statin therapy, see Paul M. Ridker et al., “Measurement of C-Reactive Protein for the Targeting of Statin Therapy in the Primary Prevention of Acute Coronary Events”; and Paul M. Ridker, “Evaluating Novel Cardiovascular Risk Factors: Can We Better Predict Heart Attacks?” in
Annals of Internal Medicine
130:11 (June 1, 1999), pages 933–937. For an understanding of the concept of risk factors, see four excellent articles in the March 2001 issue of the
American Journal of Public Health
91:3: “Risky Concepts: Methods in Cancer Research,” by Alfredo Morabia, pages 355–57; “Cancer Culture: Epidemics, Human Behavior, and the Dubious Search for New Risk Factors,” by Graham A. Colditz, pages 357–359; “The Search for Cancer Risk Factors: When Can We Stop Looking?” by Colin B. Begg, pages 360–364; and “The Privatization of Risk,” by Beverly Rockhill, pages 365–368.

Beverly Rockhill's conclusions are cogent: “It is likely,” she writes, “that the ability to predict the futures of individuals will always remain out of reach, despite ever-increasing knowledge about alleged independent factors or genes that may elevate disease risk in exposed groups.”

The dangers in “designating the individual the
sole
locus of ‘risk' and thus the locus of responsibility for ‘risk reduction,'” are twofold. First is “the amplification of existing socioeconomic health inequities, as individuals in lower socioeconomic strata are less likely to have regular contact with the health care system, to comprehend the arithmetic behind risk information, and to have the psychologic, social, and economic resources needed to voluntarily alter the factors contributing to their ‘personal' risk.”