Briefs continued from page 1235
Dollars: Prophylaxis or Cure? John C. Krantz, Jr, PhD Gibson Island, Maryland
Much is unknown about the mechanisms by which aspirin causes an increase in bleeding time by diminishing platelet aggregation. Prevailing theories of mechanisms are discussed and analyzed. The author suggests that proposed mass use of aspirin for prevention of cardiovascular diseases be delayed until current studies are fully evaluated. Louis Pasteur astutely commented, "When meditating over a disease, I *never think of a remedy for it, but instead a means of preventing it." How strikingly cogent is his message today when the dollar cost of totally controlled medical care reaches staggering figures and the budget of our nation is perpetually in the red. There is much, however, that an enlightened public could do to change this condition. It is well established that excessive smoking may produce harmful effects upon the lungs and arteries. Despite the warning of the Surgeon General, Americans smoke billions of cigarettes each year. The quantity of alcoholic beverages consumed in this country should be considered. Of distilled spirits alone the per capita consumption is 2.84 gallons per year. The public is well aware of the danger. However, despite the possibility of alcoholism and mental deterioration, the consumption continues unabated. It has been well established that overweight, lack of exercise, and an abundance of fat and salt in the diet are harbingers of hypertension, heart attack, and stroke. Yet the American diet is replete with items which have been established as responsible, in part, for diseases of the circulatory system.
Prophylaxis If those habits that are known to produce major illness and death were modified, much of the cost of comprehensive medical care would be reduced. It is important to reduce the speed of automobiles and to check the Requests for reprints should be addressed to Dr. John C. Krantz, Jr, Department of Pharmacology, University of Maryland, School of Medicine, Gibson Island, MD 21056. 1236
violence in our streets, which produce crippling and death and a staggering cost in medical care. These prophylactic measures involve the problem of the sensible control of one's personal behavior and habits. To indicate how much these changes could mean in terms of human pain and deaths and dollars, compare them to the acquisition of prophylaxis from smallpox and poliomyelitis with appropriate vaccines. These great boons to humanity and their savings in dollars are now taken for granted. Foremost among the causes of death are the diseases of the cardiovascular system. Excellent drugs such as digitalis, nitroglycerin, and the formidable list of pharmaceuticals that control hypertension are available. But there has been no prophylactic medication in cardiovascular disease conditions until recently.
Antiplatelet Aggregation by Aspirin Dr. Harvey Weiss,' hematologist at The Roosevelt Hospital in New York, made the observation in 1967 that the ingestion of aspirin evoked an increase in the bleeding time of normal individuals. The observed effect was caused by a diminishing of the aggregation of the platelets. This suggested the possibility of the use of aspirin in the prevention of diseases owing to clotting of blood in the brain, heart, or other organs. Other drugs have been shown to emulate this effect of aspirin. For example, the anti-aggregation action on the platelets is elicited by dipyridamole, sulfinpyrazone, and a number of non-steroidal antiinflammatory agents such as phenylbutazone and indomethacin. Aspirin is more effective and less toxic than any of these drugs. Of special interest is the fact that the effect on
the aggregation of platelets is not produced by sodium salicylate. It appears that the acetyl group in aspirin acetylates the platelet and this inhibits its capacity to aggregate. The effect is prolonged and likely endures throughout the life of the platelet (four to seven days). It is strange that the effect appears to depend on the specificity of the acetyl group on the salicylic acid hydroxyl group. It would be interesting to try modifications of acetic acid such as glycolic acid and aminoacetic acid. The actions of other donors of the acetyl group such as the acetylated meta and para-hydroxybenzoic acids might also prove revealing.
Prostaglandins in Prevention of Platelet Aggregation Knowledge of the mechanism of the action of aspirin in the prevention of platelet aggregation is in a state of flux. It is generally agreed that this is related to its effect upon the prostaglandins, which enjoy a multiplicity of roles in many tissue functions. PGX, one of the most recently isolated prostaglandins, plays a key role in the prevention of platelet aggregation. It is postulated that platelets impinging upon the inner lining of blood vessels release prostaglandin endoperoxides (PGE2). These cause platelet aggregation. Simultaneously, the cell wall releases an enzyme which converts the endoperoxides to PGX, thus preventing platelet clumping. Aspirin, indomethacin, and other anti-inflammatory drugs appear to block the conversion of arachidonic acid to PGE2 (which causes platelet aggregation). This allows PGX to function uninhibited in its capacity to prevent platelet aggregation.2 It is clear that understanding of this intricate mechanism is still in its incipiency and much work will be required before knowledge of it is complete. Of special interest is the ability of the aggregation to be initiated by alternative pathways so that hemostasis is not impaired in the normal person. Briefs continued on page 1237
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 71, NO. 12, 1979
Briefs continued from page 1236
Prevention of Vascular Accidents by Aspirin Reports are available from many clinical centers indicating the value of aspirin in the prevention of vascular accidents. For example, in 1974, British investigators3 reported that 600 heart attack patients who had taken one aspirin tablet daily had 25 percent fewer heart attacks than those who had taken a placebo. The evidence at hand bespeaks the benefit/risk ratio for mass medication is high. It would appear that
individuals who have suffered a heart attack or "little stroke" might reduce their chance of a second episode by the ingestion of aspirin daily. The wisdom of applying mass medication with aspirin to normal individuals who have no indication of cardiovascular disease, but are in an age group where the disease is most frequent, is questionable and should be delayed until the outcomes of the present studies have been evaluated.
Conclusion If aspirin takes its place along with other types of mass prophylactic medi-
cation such as the use of the pill to prevent pregnancy, we may, at long last, follow the suggestion of Pasteurprevention, preferred to a cure-with a savings of billions of dollars.
References 1. Weiss HJ, Aeldort LM: Impaired platelet connective tissue reaction after the ingestion of aspirin. Lancet 2:495-497, 1967 2. Vane JJ: New compound shakes up prostaglandin ideas. Chem Eng News 50:17-19, 1976 3. Elwood PC, Cochrane AL, Burr ML, et al: Randomized control trial of aspirin ingestion. Br Med J 1:436-440, 1974
Collins Heads Howard's Department of Psychiatry Dr. James L. Collins, Sr. (MD, Howard, '65), was named chairman of the Department of Psychiatry, Howard University College of Medicine on October 1, 1978. He holds the rank of associate professor. Born in Washington, DC in 1939, Dr. Collins attended the local schools and received the BS and MD degrees from Howard University in 1961 and 1965, respectively. He completed a rotating internship at Freedmen's Hospital (Washington, DC) in 1966 and a residency in psychiatry at Walter Reed General Hospital in 1972. He is certified by the American Board of Psychiatry. Dr. Collins has spent most of his medical career in the military service, on active duty or in the Reserve forces. His military experience includes: battalion surgeon, 4th BN, 41st Field Artillery, Germany, 1966-69; psychiatric resident, Walter Reed General Army Hospital, 1969-72; research psychiatrist, Walter Reed Army Institute of Research, 1972-74; chief, Department of Psychiatry, Division of Neuropsychiatry, Walter Reed Army Institute of Research, 1974; chief of psychiatry, 2290th General Hospital, US Army Reserve, Rockville, Maryland, 1975-77; surgeon, United States Army Reserve Command, Fort Meade, Maryland, 1977; and is presently commanding officer of the 92nd Field Hospital, US Army Reserve, Baltimore, Maryland. He received the Army Commendation Medal in 1969, and the Meritorious
Melwood Farm, Olney, Maryland; and Advisory Board of Human Use, Walter Reed Army Institute of Research, 1975-1978. Dr. Collins was also in the private practice of general psychiatry at 2029 Q Street, NW, Washington, DC. Dr. Collins is a member of the National Medical Association, the American Medical Association, the DC Medical Society and the American Psychiatric Association. He has six publications, of which some have appeared in this Joiurnal. * Dr. Collins and his wife Beverley have four children, James L. Jr, Lisa M., Kimberly M., and Jennifer L. Dr. James L. Collins, Sr
Service Medal in 1973. He currently holds the rank of Lt. Colonel, US Army Reserve. Dr. Collins' additional professional experience includes positions as a psychiatric consultant, Bowie State College, 1972-1973; psychiatric consultant, Metropolitan Washington Renal Dialysis Center, Bethesda, Maryland, 19711975; clinical director of the Psychiatry Services of the Washington Hospital Center, 1975; Board of Directors of the Washington Area Council of Alcoholism and Drug Abuse, 1973-1976; Professional Advisory Committee of the National Kidney Foundation, 19751977; vice-chairman, Department of Psychiatry, Washington Hospital Center, 1976- 1977; Board of Directors,
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 71, NO. 12, 1979
Publications by Dr. Collins 1. Military psychiatry. J Natl Med Assoc 64:32-33, 1972 2. Multidisciplinary consultation to a renal dialysis-kidney transplantation unit. J Natl Med Assoc 66:277-280, 1974 3. Acute psychosis in chronic renal failure: Case reports. Military Med 622-624, 1974 4. The myth of alcohol and the virile man. Addictions 3:18, 1974 5. Emotional Problems of Dialysis and Transplant Patients. Washington, DC, Virgil Smirnow Associates, Health & Public Affairs, 1977 6. A description of Walter Reed Army Medical Center's inpatient psychiatric service population, 1973-1975. J Natl Med Assoc 69:555-559, 1977 1237
Dollars: Prophylaxis or Cure? John C. Krantz, Jr, PhD Gibson Island, Maryland
Much is unknown about the mechanisms by which aspirin causes an increase in bleeding time by diminishing platelet aggregation. Prevailing theories of mechanisms are discussed and analyzed. The author suggests that proposed mass use of aspirin for prevention of cardiovascular diseases be delayed until current studies are fully evaluated. Louis Pasteur astutely commented, "When meditating over a disease, I *never think of a remedy for it, but instead a means of preventing it." How strikingly cogent is his message today when the dollar cost of totally controlled medical care reaches staggering figures and the budget of our nation is perpetually in the red. There is much, however, that an enlightened public could do to change this condition. It is well established that excessive smoking may produce harmful effects upon the lungs and arteries. Despite the warning of the Surgeon General, Americans smoke billions of cigarettes each year. The quantity of alcoholic beverages consumed in this country should be considered. Of distilled spirits alone the per capita consumption is 2.84 gallons per year. The public is well aware of the danger. However, despite the possibility of alcoholism and mental deterioration, the consumption continues unabated. It has been well established that overweight, lack of exercise, and an abundance of fat and salt in the diet are harbingers of hypertension, heart attack, and stroke. Yet the American diet is replete with items which have been established as responsible, in part, for diseases of the circulatory system.
Prophylaxis If those habits that are known to produce major illness and death were modified, much of the cost of comprehensive medical care would be reduced. It is important to reduce the speed of automobiles and to check the Requests for reprints should be addressed to Dr. John C. Krantz, Jr, Department of Pharmacology, University of Maryland, School of Medicine, Gibson Island, MD 21056. 1236
violence in our streets, which produce crippling and death and a staggering cost in medical care. These prophylactic measures involve the problem of the sensible control of one's personal behavior and habits. To indicate how much these changes could mean in terms of human pain and deaths and dollars, compare them to the acquisition of prophylaxis from smallpox and poliomyelitis with appropriate vaccines. These great boons to humanity and their savings in dollars are now taken for granted. Foremost among the causes of death are the diseases of the cardiovascular system. Excellent drugs such as digitalis, nitroglycerin, and the formidable list of pharmaceuticals that control hypertension are available. But there has been no prophylactic medication in cardiovascular disease conditions until recently.
Antiplatelet Aggregation by Aspirin Dr. Harvey Weiss,' hematologist at The Roosevelt Hospital in New York, made the observation in 1967 that the ingestion of aspirin evoked an increase in the bleeding time of normal individuals. The observed effect was caused by a diminishing of the aggregation of the platelets. This suggested the possibility of the use of aspirin in the prevention of diseases owing to clotting of blood in the brain, heart, or other organs. Other drugs have been shown to emulate this effect of aspirin. For example, the anti-aggregation action on the platelets is elicited by dipyridamole, sulfinpyrazone, and a number of non-steroidal antiinflammatory agents such as phenylbutazone and indomethacin. Aspirin is more effective and less toxic than any of these drugs. Of special interest is the fact that the effect on
the aggregation of platelets is not produced by sodium salicylate. It appears that the acetyl group in aspirin acetylates the platelet and this inhibits its capacity to aggregate. The effect is prolonged and likely endures throughout the life of the platelet (four to seven days). It is strange that the effect appears to depend on the specificity of the acetyl group on the salicylic acid hydroxyl group. It would be interesting to try modifications of acetic acid such as glycolic acid and aminoacetic acid. The actions of other donors of the acetyl group such as the acetylated meta and para-hydroxybenzoic acids might also prove revealing.
Prostaglandins in Prevention of Platelet Aggregation Knowledge of the mechanism of the action of aspirin in the prevention of platelet aggregation is in a state of flux. It is generally agreed that this is related to its effect upon the prostaglandins, which enjoy a multiplicity of roles in many tissue functions. PGX, one of the most recently isolated prostaglandins, plays a key role in the prevention of platelet aggregation. It is postulated that platelets impinging upon the inner lining of blood vessels release prostaglandin endoperoxides (PGE2). These cause platelet aggregation. Simultaneously, the cell wall releases an enzyme which converts the endoperoxides to PGX, thus preventing platelet clumping. Aspirin, indomethacin, and other anti-inflammatory drugs appear to block the conversion of arachidonic acid to PGE2 (which causes platelet aggregation). This allows PGX to function uninhibited in its capacity to prevent platelet aggregation.2 It is clear that understanding of this intricate mechanism is still in its incipiency and much work will be required before knowledge of it is complete. Of special interest is the ability of the aggregation to be initiated by alternative pathways so that hemostasis is not impaired in the normal person. Briefs continued on page 1237
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 71, NO. 12, 1979
Briefs continued from page 1236
Prevention of Vascular Accidents by Aspirin Reports are available from many clinical centers indicating the value of aspirin in the prevention of vascular accidents. For example, in 1974, British investigators3 reported that 600 heart attack patients who had taken one aspirin tablet daily had 25 percent fewer heart attacks than those who had taken a placebo. The evidence at hand bespeaks the benefit/risk ratio for mass medication is high. It would appear that
individuals who have suffered a heart attack or "little stroke" might reduce their chance of a second episode by the ingestion of aspirin daily. The wisdom of applying mass medication with aspirin to normal individuals who have no indication of cardiovascular disease, but are in an age group where the disease is most frequent, is questionable and should be delayed until the outcomes of the present studies have been evaluated.
Conclusion If aspirin takes its place along with other types of mass prophylactic medi-
cation such as the use of the pill to prevent pregnancy, we may, at long last, follow the suggestion of Pasteurprevention, preferred to a cure-with a savings of billions of dollars.
References 1. Weiss HJ, Aeldort LM: Impaired platelet connective tissue reaction after the ingestion of aspirin. Lancet 2:495-497, 1967 2. Vane JJ: New compound shakes up prostaglandin ideas. Chem Eng News 50:17-19, 1976 3. Elwood PC, Cochrane AL, Burr ML, et al: Randomized control trial of aspirin ingestion. Br Med J 1:436-440, 1974
Collins Heads Howard's Department of Psychiatry Dr. James L. Collins, Sr. (MD, Howard, '65), was named chairman of the Department of Psychiatry, Howard University College of Medicine on October 1, 1978. He holds the rank of associate professor. Born in Washington, DC in 1939, Dr. Collins attended the local schools and received the BS and MD degrees from Howard University in 1961 and 1965, respectively. He completed a rotating internship at Freedmen's Hospital (Washington, DC) in 1966 and a residency in psychiatry at Walter Reed General Hospital in 1972. He is certified by the American Board of Psychiatry. Dr. Collins has spent most of his medical career in the military service, on active duty or in the Reserve forces. His military experience includes: battalion surgeon, 4th BN, 41st Field Artillery, Germany, 1966-69; psychiatric resident, Walter Reed General Army Hospital, 1969-72; research psychiatrist, Walter Reed Army Institute of Research, 1972-74; chief, Department of Psychiatry, Division of Neuropsychiatry, Walter Reed Army Institute of Research, 1974; chief of psychiatry, 2290th General Hospital, US Army Reserve, Rockville, Maryland, 1975-77; surgeon, United States Army Reserve Command, Fort Meade, Maryland, 1977; and is presently commanding officer of the 92nd Field Hospital, US Army Reserve, Baltimore, Maryland. He received the Army Commendation Medal in 1969, and the Meritorious
Melwood Farm, Olney, Maryland; and Advisory Board of Human Use, Walter Reed Army Institute of Research, 1975-1978. Dr. Collins was also in the private practice of general psychiatry at 2029 Q Street, NW, Washington, DC. Dr. Collins is a member of the National Medical Association, the American Medical Association, the DC Medical Society and the American Psychiatric Association. He has six publications, of which some have appeared in this Joiurnal. * Dr. Collins and his wife Beverley have four children, James L. Jr, Lisa M., Kimberly M., and Jennifer L. Dr. James L. Collins, Sr
Service Medal in 1973. He currently holds the rank of Lt. Colonel, US Army Reserve. Dr. Collins' additional professional experience includes positions as a psychiatric consultant, Bowie State College, 1972-1973; psychiatric consultant, Metropolitan Washington Renal Dialysis Center, Bethesda, Maryland, 19711975; clinical director of the Psychiatry Services of the Washington Hospital Center, 1975; Board of Directors of the Washington Area Council of Alcoholism and Drug Abuse, 1973-1976; Professional Advisory Committee of the National Kidney Foundation, 19751977; vice-chairman, Department of Psychiatry, Washington Hospital Center, 1976- 1977; Board of Directors,
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 71, NO. 12, 1979
Publications by Dr. Collins 1. Military psychiatry. J Natl Med Assoc 64:32-33, 1972 2. Multidisciplinary consultation to a renal dialysis-kidney transplantation unit. J Natl Med Assoc 66:277-280, 1974 3. Acute psychosis in chronic renal failure: Case reports. Military Med 622-624, 1974 4. The myth of alcohol and the virile man. Addictions 3:18, 1974 5. Emotional Problems of Dialysis and Transplant Patients. Washington, DC, Virgil Smirnow Associates, Health & Public Affairs, 1977 6. A description of Walter Reed Army Medical Center's inpatient psychiatric service population, 1973-1975. J Natl Med Assoc 69:555-559, 1977 1237
