a complicated process. In the Coronary Drug Project, the mortality results, which in themselves give
ways
little or no evidence of benefit for either clofibrate or niacin—were weighed together with the incidence of nonfatal cardiovascular events, lipid effects, side effects including bio¬ chemical and hématologie responses, and findings in special subgroups of patients to come up with the follow¬ ing conclusion: The Coronary Drug Project provides no evidence on which to recommend the use of clofibrate in the treatment of persons with coronary heart disease, [and] because of the excess incidence of arrhythmias, gas¬ trointestinal problems, and abnormal chemistry findings in the niacin group, great care and caution must be exercised if this drug is used for treatment of persons with coronary heart disease. The Coronary Drug Project Research Group 1. The Coronary Drug Project: Design, methods, and baseline results, Coronary Drug Project Research Group. Circulation 47(suppl 1):11-150, 1973.
Factors
Favoring
Acute Myocardial Infarction To the Editor.\p=m-\Theeditorial, "Shrinking the Myocardial Infarct," (230:1310, 1974) draws attention to possible factors that may produce the opposite effect of extending rather than shrinking an infarct and to the usefulness of this knowledge in the prognosis of acute myocardial infarction (AMI) and in the saving of life. We1 have reported (1) the secondary extension of an infarct in a small group of patients out of a larger number receiving treatment for AMI and (2) the occurrence of AMI in cases that were initially diagnosed as intermediate coronary syndrome and for which treatment had been given. These effects have been noted by others.2-3 We wish to stress (1) that in both these groups, the second episode (AMI) occurred during active management of the initial event and (2) that in both types a distinct interval existed between the two episodes. Such behavior can be inferred as good evidence favoring the existence of acute in¬
farction-promoting factors,
some¬
what similar or identical to those referred to in your editorial. Further¬ more, from a practical point of view, we must regretfully admit that the factors immediately responsible for bringing about an AMI have not been halted by our treatment, however so¬ phisticated. The nature of these fac¬ tors is not clear to anybody at the moment.
If such factors do operate, we would like to refer to a more reward¬ ing application of such knowledge in the therapy of AMI than even in the reduction of the size of an already infarcted myocardium. In our main study,4 we showed that in about a quarter of the cases in which a final diagnosis of AMI had been made ac¬ cording to electrocardiographic crite¬ ria, pathologic ECG changes did not appear till 24 hours after the onset of the initial episode. In some respects, these patients may be regarded as falling somewhere between those who would have an undisputed AMI soon after the initial symptoms and those who at first have an intermediate coronary syndrome and then later, infarct. Both experimental5 and au¬ topsy6 correlative studies suggest that definitive ECG changes in the presence of a histopathologically de¬ finable infarct appear not later than at six hours. In other words, accord¬ ing to the criteria of our study, one quarter of the patients—and possibly more according to other correlatesshould possess viable, in contrast to
nonsalvageable, myocardial parenchymal tissue on admission to hospital. The knowledge of factors that pre¬ sumably bring about acute infarction of myocardium should help us to de¬ vise means to save the myocardium of this large group of patients who now progress to full-blown infarction.
Donald A. Rajapakse, MBBS, MRCP Canadian Red Cross Memorial Hospital
Berkshire, England David R. Gunraj, MBBS, MRCP
Kingston Hospital Surrey, England 1. Rajapakse DA, Gunraj DR: Prevention of some infarcts in the myocardium. Lancet 2:1202, 1974. 2. Skjaeggestad O: The natural history of intermediate coronary syndrome. Acta Med Scand 193:533\x=req-\ 536, 1973. 3. Skjaeggestad O, Berstad A: Arrhythmias in the early phase of acute myocardial infarction. Acta Med Scand 196:271-274, 1974. 4. Gunraj DR, Rajapakse DA: Daily ECG confirmation in acute myocardial infarction. Practitioner 213:361-364, 1974. 5. Smith
GT, Soeter JR, Haston HH, et al: Coronary reperfusion in primates. J Clin Invest 54:1420-1427,1974. 6. Klionsky B: Myocardial ischaemia and early infarction. Am J Pathol
36:575-592,
1960.
(1) In self-limited ITP, severe thrombocytopenia may persist for as long as four months. (2) There was no evidence that splenectomy had a favor-
able influence on the course of self\x=req-\ limited ITP. (3) Medical treatment of 54 attacks of purpura occurring in 30 patients (including chronic and self\x=req-\ limited types) resulted in three deaths and in one severe and three mild cerebral hemorrhages. There were three deaths and one postoperative cerebral embolus in 19 attacks of purpura treated by splenectomy. The rise in platelet count in the patient described by Lightsey et al2 occurred within four months after the onset of severe bleeding. The course of this patient's illness was thus no different from similar episodes treated medically when platelet transfusions, steroids, and immunosuppressive therapy were not avail¬ able. In view of the fact that splenec¬ tomy during an episode of purpura carries a significantly higher mortal¬ ity than simple supportive measures do, it seems unwise to perform sple¬ nectomy during such an episode, even if at the time one cannot be sure that spontaneous recovery will occur even¬ tually. Splenectomy should be per¬ formed only when it is evident that the thrombocytopenia is the chronic type (persisting for at least four months) and when the patient is not suffering from purpura at the time of the operation. When managing such a dramatic illness, there is great pressure on phy¬ sicians to "do something" and to at¬ tach the label "aggressive" to ther¬ apies that have not been proved to be of value. In chronic
and, sive
To the Editor.\p=m-\Thedistinction between the chronic and self-limited
types of idiopathic thrombocytopenic
(ITP) was first drawn in 1951 the basis of a study of 89 cases of ITP in the presteroid days.1 Three points made in this review are worth reemphasizing at this time: purpura
on
Downloaded From: http://jama.jamanetwork.com/ by a University of California - San Diego User on 06/13/2015
ITP, steroids recently, immunosuppres-
therapy3 have been shown to be effective, but in self-limited ITP, platelet transfusions, immunosuppressive therapy, and steroids have not been shown to be of value. The need to conserve expensive medical
should restrain the impulse employ therapies that, in spite of
resources
to
Idiopathic Thrombocytopenic Purpura
more
efforts to prove their efficacy, have not been shown to be effective. On this basis alone, the continued use of intravenously given steroids and of platelet transfusions is questionable. Moreover, in the case reported, these measures failed to influence the course of the disease. {Post hoc, ergo propter hoc reasoning provides as
good a case that these measures were harmful to the patient as that they were beneficial.)
,
of immunosuppressive therapy, it could be ar¬ gued that this therapy has never been given an adequate trial in self-lim¬ ited ITP. It is essential, however, that such trials be interpreted in the light of what is known about the natural course of the disease. In defense of the
use
Erwin O. Hirsch, MD Medical College of Wisconsin Milwaukee 1. Hirsch EO, Dameshek W: "Idiopathic" thrombocytothe penia: Review of 89 cases with particular reference to and differentiation and treatment of acute (self-limited)
chronic types. Arch Intern Med 88:701-728, 1951. 2. Lightsey AL Jr, McMillan R, Koenig HM: Childhood idiopathic thrombocytopenic purpura: Aggressive management of life-threatening complications. JAMA 232:734-736, 1975. 3. Ahn YS, Harrington WJ, Seelman RC, et al: Vincristine therapy of idiopathic and secondary thrombocytopenias. N Engl J Med 291:376-380, 1974.
Pleasures and Tragedies of Death To the Editor.\p=m-\Inthe May 19, 1975, issue of The Journal, two articles described the death of two patients from advanced malignant diseases.
In one, the patient participated in guiding his life through itthe dying phase of his disease when was clear that reasonable therapy could not alter the eventual outcome. The second patient, a physician, failed to recognize the advantages of conventional medical treatment and underwent the natural course of cancer of the prostate without reasonable therapy, possibly terminating a useful life pre-
maturely.
Lindbergh died of a malignant lymphoma that had been treated with radiotherapy and chemotherapy (232:715, 1975). In this instance, unfortunately, the therapy Charles A.
not as effective as in other patients with similar disease. Once it was recognized that medical efforts no longer could reverse the progress of the lymphoma, the patient made a just decision about the environment in which his death would occur in dignity and with personal satisfaction. The death of Prof William Kerppola was a demonstration of a physi¬ cian's selection of his method of dying without appropriate diagnosis of his disease or any specific antitumor treatment (232:728,1975). Despite the professor's age of more than 80 years, this metastatic carcinoma of the pros¬ tate could have been treated, result¬ ing in relief of pain and rehabili¬ tation. Not to have imposed a few simple diagnostic tests and a few mil¬ ligrams of estrogenic hormone re¬ sulted in the tragic loss of a life, probwas
subjects on the megadose regimen of ascorbic acid may well be at risk for ultimate development of vitamin B12 deficiency. All of these subjects are being followed up with monthly determina¬ tions of serum vitamin B12 levels. In one subject, within three months the
ably prematurely. The conventional
to 3% of
physician should provide a patient. Although everyone should have the right to die and to involve himself in the decision-making, it does seem a tragedy when a patient with cancer undergoes a painful phase of dying whereas treatment might have pre¬ vented this distress, possibly allowing
level increased from 100 to 180 pg/ml, a substantial increase simply following cessation of the megadose regimen of ascorbic acid.
treatment of carcinoma of the pros¬ tate is not new, not "inhumane," and well within the realm of what every
death to occur later from sudden vas¬ cular disease. This is an outstanding example in which the diagnosis would have been of value, and in my opinion it was not "in the best interests of the patient to abandon the search for it." B. J. Kennedy, MD Section of Medical Oncology University of Minnesota School
of Medicine
Minneapolis
Ascorbic Acid and Vitamin B12 Deficiency To the Editor.\p=m-\DrsHerbert and Jacob made the observation that ascorbic acid (vitamin C) in quantities in excess of 0.5 gm will destroy between 50% and 95% of vitamin B12 content in food (230:241, 1974). During the past six months, we have been able to assess the vitamin B12 concentrations in serum as well as in the peripheral blood smears in 90
at Cleveland Metropolitan General Hospital, all taking more
subjects
than 500 mg of ascorbic acid daily. These subjects responded to publicity
concerning the possible danger of
megadose ascorbic acid ingestion. Three subjects, aged 50 to 60 years, had been taking a minimum of 1,000
mg of ascorbic acid with each meal for more than three years. These three subjects did show subnormal serum vitamin B12 concentrations ranging from 65 to 100 pg/ml. Two of the three had hypersegmented neutrophils and occasional ovalomacrocytes, although none were anemic, indicative of a morphologic expression of vitamin B12 deficiency. All of the patients had normal gastric intrin¬ sic factor as analyzed by radioimmunoassay; none of these subjects had a history of pernicious anemia, nor did they have antibody to intrin¬ sic factors circulating in serum or in gastric juice. A substantial number of these subjects were also taking oral crude liver extract or other substances containing substantial amounts of vitamin B12. The conclusion is that possibly 2%
serum
John D. Hines, MD
Cleveland
Sticking Sheets To the Editor.\p=m-\Ihave a suggestion that I think would benefit other nurses and some patients. At the hospital where I am employed, we had a patient with psoriasis. The patient had large draining blisters over his body, and everytime he was turned he would stick to the sheets. I suggested using a vegetable oil spray, Pam, on the sheets. We tried Pam and it worked. The patient didn't stick to the sheets. It might be used for burn cases also. Sharon Baugh, RN
Indianapolis
This is
a
brave
repeated widely,
experiment. Before
assurance
it is is needed that
Pam is sterile.—Ed.
Defensive Medicine Disdained On a recent Saturday evening at St
James Hospital, Chicago Heights, Ill, Drs Norman R. Brill, Branislav M. Dragisic, Aaron B. Gerber, and Clifford W. Smith, together with their surgical team, battled unfavorable odds and rescued me from a ruptured abdominal aortic aneurysm, complicated by free rupture into the peritoneal cavity and shock before surgery. Faced with the obvious probability of a bad result, they could have played "safe" from "malpractice" allegations by getting extra consultation, ordering a few more tests, and wasting some time. Had they done so, I would be dead. Instead, they made the probable diagnosis quickly, prepared for surgery with as much speed as was in my interest, and went to work to do what was required. Clearly, I owe my life to the knowledge, skill, and dedication of these physicians, but something more is involved. I also owe it to the fact that not all physicians have been intimidated by current legal trends and in¬ fluences into practicing "defensive medicine." MD
Downloaded From: http://jama.jamanetwork.com/ by a University of California - San Diego User on 06/13/2015
John Archer,
ways
little or no evidence of benefit for either clofibrate or niacin—were weighed together with the incidence of nonfatal cardiovascular events, lipid effects, side effects including bio¬ chemical and hématologie responses, and findings in special subgroups of patients to come up with the follow¬ ing conclusion: The Coronary Drug Project provides no evidence on which to recommend the use of clofibrate in the treatment of persons with coronary heart disease, [and] because of the excess incidence of arrhythmias, gas¬ trointestinal problems, and abnormal chemistry findings in the niacin group, great care and caution must be exercised if this drug is used for treatment of persons with coronary heart disease. The Coronary Drug Project Research Group 1. The Coronary Drug Project: Design, methods, and baseline results, Coronary Drug Project Research Group. Circulation 47(suppl 1):11-150, 1973.
Factors
Favoring
Acute Myocardial Infarction To the Editor.\p=m-\Theeditorial, "Shrinking the Myocardial Infarct," (230:1310, 1974) draws attention to possible factors that may produce the opposite effect of extending rather than shrinking an infarct and to the usefulness of this knowledge in the prognosis of acute myocardial infarction (AMI) and in the saving of life. We1 have reported (1) the secondary extension of an infarct in a small group of patients out of a larger number receiving treatment for AMI and (2) the occurrence of AMI in cases that were initially diagnosed as intermediate coronary syndrome and for which treatment had been given. These effects have been noted by others.2-3 We wish to stress (1) that in both these groups, the second episode (AMI) occurred during active management of the initial event and (2) that in both types a distinct interval existed between the two episodes. Such behavior can be inferred as good evidence favoring the existence of acute in¬
farction-promoting factors,
some¬
what similar or identical to those referred to in your editorial. Further¬ more, from a practical point of view, we must regretfully admit that the factors immediately responsible for bringing about an AMI have not been halted by our treatment, however so¬ phisticated. The nature of these fac¬ tors is not clear to anybody at the moment.
If such factors do operate, we would like to refer to a more reward¬ ing application of such knowledge in the therapy of AMI than even in the reduction of the size of an already infarcted myocardium. In our main study,4 we showed that in about a quarter of the cases in which a final diagnosis of AMI had been made ac¬ cording to electrocardiographic crite¬ ria, pathologic ECG changes did not appear till 24 hours after the onset of the initial episode. In some respects, these patients may be regarded as falling somewhere between those who would have an undisputed AMI soon after the initial symptoms and those who at first have an intermediate coronary syndrome and then later, infarct. Both experimental5 and au¬ topsy6 correlative studies suggest that definitive ECG changes in the presence of a histopathologically de¬ finable infarct appear not later than at six hours. In other words, accord¬ ing to the criteria of our study, one quarter of the patients—and possibly more according to other correlatesshould possess viable, in contrast to
nonsalvageable, myocardial parenchymal tissue on admission to hospital. The knowledge of factors that pre¬ sumably bring about acute infarction of myocardium should help us to de¬ vise means to save the myocardium of this large group of patients who now progress to full-blown infarction.
Donald A. Rajapakse, MBBS, MRCP Canadian Red Cross Memorial Hospital
Berkshire, England David R. Gunraj, MBBS, MRCP
Kingston Hospital Surrey, England 1. Rajapakse DA, Gunraj DR: Prevention of some infarcts in the myocardium. Lancet 2:1202, 1974. 2. Skjaeggestad O: The natural history of intermediate coronary syndrome. Acta Med Scand 193:533\x=req-\ 536, 1973. 3. Skjaeggestad O, Berstad A: Arrhythmias in the early phase of acute myocardial infarction. Acta Med Scand 196:271-274, 1974. 4. Gunraj DR, Rajapakse DA: Daily ECG confirmation in acute myocardial infarction. Practitioner 213:361-364, 1974. 5. Smith
GT, Soeter JR, Haston HH, et al: Coronary reperfusion in primates. J Clin Invest 54:1420-1427,1974. 6. Klionsky B: Myocardial ischaemia and early infarction. Am J Pathol
36:575-592,
1960.
(1) In self-limited ITP, severe thrombocytopenia may persist for as long as four months. (2) There was no evidence that splenectomy had a favor-
able influence on the course of self\x=req-\ limited ITP. (3) Medical treatment of 54 attacks of purpura occurring in 30 patients (including chronic and self\x=req-\ limited types) resulted in three deaths and in one severe and three mild cerebral hemorrhages. There were three deaths and one postoperative cerebral embolus in 19 attacks of purpura treated by splenectomy. The rise in platelet count in the patient described by Lightsey et al2 occurred within four months after the onset of severe bleeding. The course of this patient's illness was thus no different from similar episodes treated medically when platelet transfusions, steroids, and immunosuppressive therapy were not avail¬ able. In view of the fact that splenec¬ tomy during an episode of purpura carries a significantly higher mortal¬ ity than simple supportive measures do, it seems unwise to perform sple¬ nectomy during such an episode, even if at the time one cannot be sure that spontaneous recovery will occur even¬ tually. Splenectomy should be per¬ formed only when it is evident that the thrombocytopenia is the chronic type (persisting for at least four months) and when the patient is not suffering from purpura at the time of the operation. When managing such a dramatic illness, there is great pressure on phy¬ sicians to "do something" and to at¬ tach the label "aggressive" to ther¬ apies that have not been proved to be of value. In chronic
and, sive
To the Editor.\p=m-\Thedistinction between the chronic and self-limited
types of idiopathic thrombocytopenic
(ITP) was first drawn in 1951 the basis of a study of 89 cases of ITP in the presteroid days.1 Three points made in this review are worth reemphasizing at this time: purpura
on
Downloaded From: http://jama.jamanetwork.com/ by a University of California - San Diego User on 06/13/2015
ITP, steroids recently, immunosuppres-
therapy3 have been shown to be effective, but in self-limited ITP, platelet transfusions, immunosuppressive therapy, and steroids have not been shown to be of value. The need to conserve expensive medical
should restrain the impulse employ therapies that, in spite of
resources
to
Idiopathic Thrombocytopenic Purpura
more
efforts to prove their efficacy, have not been shown to be effective. On this basis alone, the continued use of intravenously given steroids and of platelet transfusions is questionable. Moreover, in the case reported, these measures failed to influence the course of the disease. {Post hoc, ergo propter hoc reasoning provides as
good a case that these measures were harmful to the patient as that they were beneficial.)
,
of immunosuppressive therapy, it could be ar¬ gued that this therapy has never been given an adequate trial in self-lim¬ ited ITP. It is essential, however, that such trials be interpreted in the light of what is known about the natural course of the disease. In defense of the
use
Erwin O. Hirsch, MD Medical College of Wisconsin Milwaukee 1. Hirsch EO, Dameshek W: "Idiopathic" thrombocytothe penia: Review of 89 cases with particular reference to and differentiation and treatment of acute (self-limited)
chronic types. Arch Intern Med 88:701-728, 1951. 2. Lightsey AL Jr, McMillan R, Koenig HM: Childhood idiopathic thrombocytopenic purpura: Aggressive management of life-threatening complications. JAMA 232:734-736, 1975. 3. Ahn YS, Harrington WJ, Seelman RC, et al: Vincristine therapy of idiopathic and secondary thrombocytopenias. N Engl J Med 291:376-380, 1974.
Pleasures and Tragedies of Death To the Editor.\p=m-\Inthe May 19, 1975, issue of The Journal, two articles described the death of two patients from advanced malignant diseases.
In one, the patient participated in guiding his life through itthe dying phase of his disease when was clear that reasonable therapy could not alter the eventual outcome. The second patient, a physician, failed to recognize the advantages of conventional medical treatment and underwent the natural course of cancer of the prostate without reasonable therapy, possibly terminating a useful life pre-
maturely.
Lindbergh died of a malignant lymphoma that had been treated with radiotherapy and chemotherapy (232:715, 1975). In this instance, unfortunately, the therapy Charles A.
not as effective as in other patients with similar disease. Once it was recognized that medical efforts no longer could reverse the progress of the lymphoma, the patient made a just decision about the environment in which his death would occur in dignity and with personal satisfaction. The death of Prof William Kerppola was a demonstration of a physi¬ cian's selection of his method of dying without appropriate diagnosis of his disease or any specific antitumor treatment (232:728,1975). Despite the professor's age of more than 80 years, this metastatic carcinoma of the pros¬ tate could have been treated, result¬ ing in relief of pain and rehabili¬ tation. Not to have imposed a few simple diagnostic tests and a few mil¬ ligrams of estrogenic hormone re¬ sulted in the tragic loss of a life, probwas
subjects on the megadose regimen of ascorbic acid may well be at risk for ultimate development of vitamin B12 deficiency. All of these subjects are being followed up with monthly determina¬ tions of serum vitamin B12 levels. In one subject, within three months the
ably prematurely. The conventional
to 3% of
physician should provide a patient. Although everyone should have the right to die and to involve himself in the decision-making, it does seem a tragedy when a patient with cancer undergoes a painful phase of dying whereas treatment might have pre¬ vented this distress, possibly allowing
level increased from 100 to 180 pg/ml, a substantial increase simply following cessation of the megadose regimen of ascorbic acid.
treatment of carcinoma of the pros¬ tate is not new, not "inhumane," and well within the realm of what every
death to occur later from sudden vas¬ cular disease. This is an outstanding example in which the diagnosis would have been of value, and in my opinion it was not "in the best interests of the patient to abandon the search for it." B. J. Kennedy, MD Section of Medical Oncology University of Minnesota School
of Medicine
Minneapolis
Ascorbic Acid and Vitamin B12 Deficiency To the Editor.\p=m-\DrsHerbert and Jacob made the observation that ascorbic acid (vitamin C) in quantities in excess of 0.5 gm will destroy between 50% and 95% of vitamin B12 content in food (230:241, 1974). During the past six months, we have been able to assess the vitamin B12 concentrations in serum as well as in the peripheral blood smears in 90
at Cleveland Metropolitan General Hospital, all taking more
subjects
than 500 mg of ascorbic acid daily. These subjects responded to publicity
concerning the possible danger of
megadose ascorbic acid ingestion. Three subjects, aged 50 to 60 years, had been taking a minimum of 1,000
mg of ascorbic acid with each meal for more than three years. These three subjects did show subnormal serum vitamin B12 concentrations ranging from 65 to 100 pg/ml. Two of the three had hypersegmented neutrophils and occasional ovalomacrocytes, although none were anemic, indicative of a morphologic expression of vitamin B12 deficiency. All of the patients had normal gastric intrin¬ sic factor as analyzed by radioimmunoassay; none of these subjects had a history of pernicious anemia, nor did they have antibody to intrin¬ sic factors circulating in serum or in gastric juice. A substantial number of these subjects were also taking oral crude liver extract or other substances containing substantial amounts of vitamin B12. The conclusion is that possibly 2%
serum
John D. Hines, MD
Cleveland
Sticking Sheets To the Editor.\p=m-\Ihave a suggestion that I think would benefit other nurses and some patients. At the hospital where I am employed, we had a patient with psoriasis. The patient had large draining blisters over his body, and everytime he was turned he would stick to the sheets. I suggested using a vegetable oil spray, Pam, on the sheets. We tried Pam and it worked. The patient didn't stick to the sheets. It might be used for burn cases also. Sharon Baugh, RN
Indianapolis
This is
a
brave
repeated widely,
experiment. Before
assurance
it is is needed that
Pam is sterile.—Ed.
Defensive Medicine Disdained On a recent Saturday evening at St
James Hospital, Chicago Heights, Ill, Drs Norman R. Brill, Branislav M. Dragisic, Aaron B. Gerber, and Clifford W. Smith, together with their surgical team, battled unfavorable odds and rescued me from a ruptured abdominal aortic aneurysm, complicated by free rupture into the peritoneal cavity and shock before surgery. Faced with the obvious probability of a bad result, they could have played "safe" from "malpractice" allegations by getting extra consultation, ordering a few more tests, and wasting some time. Had they done so, I would be dead. Instead, they made the probable diagnosis quickly, prepared for surgery with as much speed as was in my interest, and went to work to do what was required. Clearly, I owe my life to the knowledge, skill, and dedication of these physicians, but something more is involved. I also owe it to the fact that not all physicians have been intimidated by current legal trends and in¬ fluences into practicing "defensive medicine." MD
Downloaded From: http://jama.jamanetwork.com/ by a University of California - San Diego User on 06/13/2015
John Archer,
