Being Single James J. Lynch, professor of psychology
Microbial Modulation of
Hazards of
the University of Maryland School of Medicine, proposes that lack of human companionship is one of the leading causes of premature death in America. In The Broken Heart (New York, Basic Books, 1977), he makes a cogent case that death rates are higher in single, widowed, separated, or divorced subjects than in married persons. If that is so, then Dr Lynch may have made the strongest case yet for that frail social institution of marriage. One of the more striking outcomes of Lynch's research is that not just cardiovascular disease but all other major causes of death take a higher toll in unmarried than in married persons. Why that should be is by no means obvious; perhaps the very process of selection removes the sick from the marriageable pool, as they are less likely to find a partner. However, selection alone is unlikely to be the sole determinant, and other influences must exist. Perhaps it is restless life-style, lessened concern for self, later detection of illness. And what about the married person living in discord with, or in virtual social isolation from, his or her spouse? Insurance companies have long recognized that unmarried persons present them with a greater risk of dying prematurely. Death rates in the 15- to 64-year age bracket of divorced males, for instance, were from two to six times higher for every major cause than those of married males (1959 to 1961). Higher death rates in divorced vs married persons even included cancer within the same period, certainly a startling observation that defies facile explanation. The phenomenon is by no means limited to the United States; single life appears to be as hazardous to one's health in other industrialized countries, though the ratios vary. Whatever the cause, social isolation has a hand in premature death, taking its greatest toll in coronary disease. Should we add loneliness to the many risk factors contributing to heart disease (obesity, smoking, drinking, lack of exercise)? We do not know for sure, but perhaps we should look at lack of human companionship as a stress that raises the likelihood of premature heart disease. As Lynch is quick to point out, it is not being single itself that is hazardous, but rather one's social and mental adjustment to life alone. Many single persons live satisfying, loving lives, whereas many married persons live in virtual emotional isola¬ tion. Evidently, it is the absence of human companionship that is detrimental. Emotional support in times of stress is a pervasive and universal human need: a mere touch has soothed the comatose patient. Interpersonal rejection, conversely, makes it more difficult to deal with life's stresses. In fact, many patients need contact with another human being more than they need medical attention. As Lynch puts it, "loneliness can damage, if not break, the human heart." The message is clear: either learn of dying before your time. risk the chance to live together or Rudolph H. de Jong, MD at
Granulopoiesis
It is well known that microorganisms can be tied into the metabolism and the regulatory network of the human organism. Intestinal bacteria, for instance, participate in a large number of the host's metabolic processes. They synthesize vitamins, particularly those of the B complex family. They convert cholesterol to coprostanol, and fatty acids to corresponding alcohols. They deaminate amino acids and degrade them to indole, skatole, methane, ammonia, and benzoic acid. Furthermore, they deconjugate bile acids\p=m-\ametabolic process that involves a feedback loop, wherein the dampening arm is the bactericidal action of the deconjugated acids. By destroying the bacteria responsible for the deconjugation, its products regulate the rate of their own production. Regulatory feedback interactions between bacteria and their human hosts may be even more intricate, as suggested by recent studies on the regulation of granulopoiesis. It has been known for some time that bacterial endotoxins stimulate mononuclear cells, preponderantly monocytes, to secrete granulopoietic factors, collectively known as colony-stimulating factor (csf), which in turn stimulates the formation of neutrophilic granulocytes.' A simple direct negative feedback loop between the granulocytes and the csf was assumed to modulate the rate of granulopoiesis with excessive granulocyte produc¬ tion acting as an inhibitor to csf secretion. In this schema, bacteria played no role beyond the original stimulation of csf secretion. Robinson et al2 cast doubt on the validity of this schema. They introduced live Staphylococcus epidermidis into mononu¬ clear cell cultures, thereby enhancing csf production. This enhancement was promptly inhibited when peripheral blood granulocytes, added to the cultures, destroyed the bacteria. Apparently, the bactericidal action of granulocytes rather than their inhibiting effect on csf completed the negative feedback loop. Bacteria may thus play a pivotal role in granulopoiesis. They initiate the process by stimulating mononuclear cells, and
they
suppress it
by indirectly increasing granulocyte produc¬
tion, thereby ensuring their own destruction. Feedback mechanisms, whether direct or indirect, lie
at the of medicine and biology. Contrary to widespread impres¬ sion, the cybernetic concept did not originate with the physi¬ cist-engineer Norbert Wiener, who gave it its name and extended its applicability, but with the physiologist Claude Bernard (the centenary of his death is commemorated this year). Bernard's "milieu intérieur" and Walter Cannon's "homeostasis" are variations on the cybernetic theme. Clearly, the incorpo¬ ration of microorganisms into the human internal environnient is in harmony with the newer insights into ecological unity. core
Samuel Vaisrub, MD al: Effect of endotoxin on granulopoiesis and the in vitro colony-forming cell. Blood 41:391-398, 1973. 2. Robinson WA, Entringer MA, Bolin RW, et al: Bacterial stimulation and granulocyte inhibition of granulopoietic factor production. N Engl J Med 297:1129-1134, 1977. 1.
Quesenberry P, Morley A, Miller M,
Address editorial communications to the Editor, 535 N Dearborn St, Chicago, IL 60610.
Downloaded From: http://jama.jamanetwork.com/ by a RYERSON UNIVERSITY LIBRARY User on 06/15/2015
et
Microbial Modulation of
Hazards of
the University of Maryland School of Medicine, proposes that lack of human companionship is one of the leading causes of premature death in America. In The Broken Heart (New York, Basic Books, 1977), he makes a cogent case that death rates are higher in single, widowed, separated, or divorced subjects than in married persons. If that is so, then Dr Lynch may have made the strongest case yet for that frail social institution of marriage. One of the more striking outcomes of Lynch's research is that not just cardiovascular disease but all other major causes of death take a higher toll in unmarried than in married persons. Why that should be is by no means obvious; perhaps the very process of selection removes the sick from the marriageable pool, as they are less likely to find a partner. However, selection alone is unlikely to be the sole determinant, and other influences must exist. Perhaps it is restless life-style, lessened concern for self, later detection of illness. And what about the married person living in discord with, or in virtual social isolation from, his or her spouse? Insurance companies have long recognized that unmarried persons present them with a greater risk of dying prematurely. Death rates in the 15- to 64-year age bracket of divorced males, for instance, were from two to six times higher for every major cause than those of married males (1959 to 1961). Higher death rates in divorced vs married persons even included cancer within the same period, certainly a startling observation that defies facile explanation. The phenomenon is by no means limited to the United States; single life appears to be as hazardous to one's health in other industrialized countries, though the ratios vary. Whatever the cause, social isolation has a hand in premature death, taking its greatest toll in coronary disease. Should we add loneliness to the many risk factors contributing to heart disease (obesity, smoking, drinking, lack of exercise)? We do not know for sure, but perhaps we should look at lack of human companionship as a stress that raises the likelihood of premature heart disease. As Lynch is quick to point out, it is not being single itself that is hazardous, but rather one's social and mental adjustment to life alone. Many single persons live satisfying, loving lives, whereas many married persons live in virtual emotional isola¬ tion. Evidently, it is the absence of human companionship that is detrimental. Emotional support in times of stress is a pervasive and universal human need: a mere touch has soothed the comatose patient. Interpersonal rejection, conversely, makes it more difficult to deal with life's stresses. In fact, many patients need contact with another human being more than they need medical attention. As Lynch puts it, "loneliness can damage, if not break, the human heart." The message is clear: either learn of dying before your time. risk the chance to live together or Rudolph H. de Jong, MD at
Granulopoiesis
It is well known that microorganisms can be tied into the metabolism and the regulatory network of the human organism. Intestinal bacteria, for instance, participate in a large number of the host's metabolic processes. They synthesize vitamins, particularly those of the B complex family. They convert cholesterol to coprostanol, and fatty acids to corresponding alcohols. They deaminate amino acids and degrade them to indole, skatole, methane, ammonia, and benzoic acid. Furthermore, they deconjugate bile acids\p=m-\ametabolic process that involves a feedback loop, wherein the dampening arm is the bactericidal action of the deconjugated acids. By destroying the bacteria responsible for the deconjugation, its products regulate the rate of their own production. Regulatory feedback interactions between bacteria and their human hosts may be even more intricate, as suggested by recent studies on the regulation of granulopoiesis. It has been known for some time that bacterial endotoxins stimulate mononuclear cells, preponderantly monocytes, to secrete granulopoietic factors, collectively known as colony-stimulating factor (csf), which in turn stimulates the formation of neutrophilic granulocytes.' A simple direct negative feedback loop between the granulocytes and the csf was assumed to modulate the rate of granulopoiesis with excessive granulocyte produc¬ tion acting as an inhibitor to csf secretion. In this schema, bacteria played no role beyond the original stimulation of csf secretion. Robinson et al2 cast doubt on the validity of this schema. They introduced live Staphylococcus epidermidis into mononu¬ clear cell cultures, thereby enhancing csf production. This enhancement was promptly inhibited when peripheral blood granulocytes, added to the cultures, destroyed the bacteria. Apparently, the bactericidal action of granulocytes rather than their inhibiting effect on csf completed the negative feedback loop. Bacteria may thus play a pivotal role in granulopoiesis. They initiate the process by stimulating mononuclear cells, and
they
suppress it
by indirectly increasing granulocyte produc¬
tion, thereby ensuring their own destruction. Feedback mechanisms, whether direct or indirect, lie
at the of medicine and biology. Contrary to widespread impres¬ sion, the cybernetic concept did not originate with the physi¬ cist-engineer Norbert Wiener, who gave it its name and extended its applicability, but with the physiologist Claude Bernard (the centenary of his death is commemorated this year). Bernard's "milieu intérieur" and Walter Cannon's "homeostasis" are variations on the cybernetic theme. Clearly, the incorpo¬ ration of microorganisms into the human internal environnient is in harmony with the newer insights into ecological unity. core
Samuel Vaisrub, MD al: Effect of endotoxin on granulopoiesis and the in vitro colony-forming cell. Blood 41:391-398, 1973. 2. Robinson WA, Entringer MA, Bolin RW, et al: Bacterial stimulation and granulocyte inhibition of granulopoietic factor production. N Engl J Med 297:1129-1134, 1977. 1.
Quesenberry P, Morley A, Miller M,
Address editorial communications to the Editor, 535 N Dearborn St, Chicago, IL 60610.
Downloaded From: http://jama.jamanetwork.com/ by a RYERSON UNIVERSITY LIBRARY User on 06/15/2015
et
