Letters, if clearly marked "For Publication," will be published
as space permits and at the discretion of the editor. They should be typewritten triple-spaced, with five or fewer references, should not exceed two pages in length, and will be subject to editing. Letters
are
not
acknowledged.
Propoxyphene Overdose Deaths To the Editor.\p=m-\Weare observing an alarming increase in North Carolina
in the number of deaths attributable to propoxyphene. We doubt that the phenomenon is peculiar to this state. Most physicians may not be aware of the problem, in spite of the article in
by Sturner and Garriott (223:1125, 1973). This state's Medical Examiner Sys-
THE JOURNAL
tem detected 21 deaths in 1972 and 21 in 1973 attributable to propoxyphene.
Thirteen such deaths were identified in the first half of 1974, and 17 more in the last half of that year. In the first three months of 1975, sixteen more deaths have been recorded. In comparison, there has been an average of 39 barbiturate deaths annually from 1971 to 1974. There have been only three barbiturate deaths during the first quarter of this year, when there were 16 propoxyphene deaths. Most of the propoxyphene deaths have been suicidal overdoses; some have been accidents. Propoxyphene is a prescription analgesic second only to aspirin in popu¬ larity. The drug in the various forms of Darvon was the most commonly
in 1972. Although Darvon is the most widely used pro¬ poxyphene, it is also available as Dolene, Pro-Gesic-65, and SK-65. The relatively new napsylate salt of pro¬ poxyphene, Darvon-N, is reputed to be safer than hydrochloride salt be¬ cause of its poor solubility. We are unaware that one form of propoxy¬ phene is demonstrably safer than an¬ other. We offer several possibilities to ac¬ count for the increase in recognized propoxyphene deaths: (1) the resched¬ uling-induced decrease in availabil¬
prescribed drug
of rapid-acting barbiturates, (2) stricter controls on the much less le¬ thal analgesic codeine; (3) the mis¬ conception among many physicians that propoxyphene is essentially harmless; and (4) the situation that Medicare will pay for propoxyphene
ity
Edited
by John
D.
Archer, MD, Senior Editor.
prescriptions aspirin.
but will not pay for
Communities that
are
not detect¬
ing propoxyphene deaths may not have adequate death investigative systems including competent tox¬ icology facilities. Recent improve¬ ment in techniques may account for discovery of cases that would other¬
wise have gone undetected.1 It is our opinion that 15 to 20 of the 65-mg capsules (or of the 100-mg napsylate salt compressed tablets) may cause death, and that somewhat lesser amounts may do so with ethanol or other central nervous system depres¬ sants. In our experience, blood con¬ centrations of propoxyphene together with other depressants that exceed 0.1 mg/100 ml, and of propoxyphene alone that exceed 0.2 mg/100 ml, can cause death. Arthur J. McBay, PhD Page Hudson, MD Office of the Chief Medical Examiner Chapel Hill, NC 1. McBay AJ, Turk RF, Corbett BW, et al: Determination of propoxyphene in biological materials. J Forensic Sci 19:81-89, 1974.
Axillary Hyperhidrosis To the Editor.\p=m-\We were pleased to note the success Andersen and his col-
leagues (231:1026, 1975) have had in treating axillary hyperhidrosis in more than 250 patients by the employment of the simple surgical technique we introduced in 1963.
Although Andersen states that cur-
"topical treatment of hyperhidrosis of the axillae is, nine times out of ten, ineffective," we would like to record that we have now discovered a topical antiperspirant system that is even more effective than our simple surgical procedure. Although the method was initially outlined last year,1 it is fully detailed in a forthcoming article.2 In essence, complete axillary anhirent
drosis, as demonstrated by sustained garment armpit dryness, could regu-
larly be achieved in hyperhidrotic patients within 48 hours by the following trinary technique: (1) local application of 20% aluminum chloride
hexahydrate in anhydrous ethyl alcohol (200-proof); (2) making this application on the dry, unwashed, nonsweating axilla at the time of re¬ tiring; and (3) covering the treated area for the subsequent six to eight hours with a thin, water vapor-imper¬ meable plastic film such as vinyl chloride-vinylidine chloride copolymer sheeting (Saran Wrap). The plastic film must be kept in snug apposition to the skin by a dress-shield garment or by a well-fitted body shirt. On aris¬ ing, the patient removes the plastic film and washes the area. Subsequent application with this technique once weekly maintains the anhidrosis in¬ definitely. Walter B. Shelley, MD Harry J. Hurley, Jr, MD
Philadelphia
Shelley WB: Consultations in Dermatology II. Philadelphia, WB Saunders Co, 1974, pp 256-262. 2. Shelley WB, Hurley HJ: Studies on topical antiperspirant control of axillary hyperhidrosis. Acta Derm Venereol, to be published. 1.
Phencyclidine Poisoning To the Editor.\p=m-\Intheir article, "Hypertensive Crisis and Death Associated With Phencyclidine Poisoning" (231:1270, 1975), Eastman and Cohen attributed the death of their patient to "a direct result of the pressor ef-
fect of the drug" phencyclidine, even the acute hypertensive episode occurred three days following ingestion of the agent, at which time there was no phencyclidine detectable in his blood or urine. On that date the patient was described as "drowsy"; dilated pupils and rigidity developed, while his blood pressure was normal (140/90 mm Hg). He then became comatose, and hypertension (220/130
though
mm
Hg) and respiratory arrest devel-
He never regained consciousand died four days later. On the basis of this sequence of events, it appears that the neurological abnormalities developed before the patient be-
oped. ness
came
hypertensive.
An alternative explanation to the pathophysiology described by the authors is that the patient suffered from residual central nervous system depressant effects of the phencyclidine or from some other agent taken prior to or during his hospitalization. The resultant respiratory depression or airway obstruction or both produced acute hypoxemia with catecholamine release and its attendant finding, hy¬ pertension, causing the intracerebral hemorrhage noted on postmortem ex¬ amination. Thus, the hypertensive episode may have been the result,
Downloaded From: http://jama.jamanetwork.com/ by a Florida International University Medical Library User on 06/10/2015
rather than the cause, of the patient's neurological dysfunction. It may not be correct, therefore, to attribute this individual's death directly to the pressor effect of phencyclidine.
1. Serck-Hansen A, Purchit GP: Histiocytic medullary reticulosis. Br J Cancer 22:506-516, 1968. 2. Amsel S, Bijlsma F: Histiocytic medullary reticulosis. Trop Geogr Med 26:31-38, 1974. 3. Cline MJ, Golde DW: A review and reevaluation of histiocytic disorders. Am J Med 55:49, 1973.
Robert H. Libman, MD Illinois Masonic Medical Center
To the Editor \p=m-\DrDavid Shreiner's article was very interesting and has stimulated me to make the follow-
Chicago
Acute Lymphoblastic Leukemia And Histiocytic
Medullary Reticulocytosis
To the Editor.\p=m-\DrShreiner's article
(231:838, 1975) suggests a stem-cell abnormality as the possible underlying cause of the patient's acute
lymphoblastic leukemia and subsequent histiocytic medullary reticulosis. Further thought on the cause of the latter disease is provoked by the
existence of 25 cases of histiocytic medullary reticulosis seen at Mulago
Hospital in Uganda over a seven-year period.1-2 Good American articles often fail
to note the existence of this large number of cases.3 Serck-Hansen and Purchit have postulated that the increased incidence of cases in the tropics may be due to increased stimulation of the reticuloendothelial system, resulting from frequent infections or from malnutrition beginning in early infancy.1 It may be of additional interest that many of these cases come from the same area where there is an increased incidence of Burkitt lym-
phoma.
Robert F. Marvin, MD Drexel Hill, Pa
Fig are
ing
comments. The chest roentgenogram showed
an anterosuperior mediastinal mass that varied in size from time to time. The nature of the mass and its origin were not defined except to indicate that the mass was composed of malignant histiocytes. I suggest that the mass may have been of thymic origin and that it was the source of the abnormal cells, rather than a depository for them.1-3 The illustrations of "erythrophagocytosis" may represent such a phenomenon, but I call attention to the possibility that the globules may not be red blood cells at all, but retained
phagocytosed glycoprotein globules secreted by these cells or others of the plasma cell line. The similarity of such globules to red blood cells has often deceived me and confused many other investigaor
one is aware illustrated in the phenomenon accompanying photographs, he will make assumptions that are unwar¬ ranted, without feeling the need to double-check the identity of forms that appear quite obviously to be
tors in the
of the
past. Unless
erythrocytes.
When the cells illustrated in
1 .—Section of thymus from pregnant guinea pig. The globules eosinophilic and resemble erythrocytes (original magnifica¬
tion x
200) (from Simmons3).
Fig
1
and 2 are present in large numbers in the spleen, it requires an awareness of their presence plus very careful ex¬ amination to distinguish them from red blood cells, which may be adjacent to, above, and beneath them. If, in fact, the globules described by Dr Shreiner were not red blood cells at all, it would be less "surprising that the reticuloendothelial scan showed a great decrease in the reticu¬ loendothelial activity of the bone marrow." Vaughan P. Simmons, MD
Philadelphia 1. Simmons VP:
atrics
Thymic
function and leukemia. Pedi-
5:574-595, 1950.
diseases, globulins, plasma cells, Russell bodies, Foa-Kurloff bodies, and the thymus: A unifying concept. Wis Med J 66:349-364, 1967. 3. Simmons VP: The thymus comes to age. Trans Assoc Life Ins Med Dir Am 57:86-122, 1973. 2. Simmons VP: Diverse
Reply.\p=m-\DrSimmons may be quite right that the mediastinal mass may have been of thymic origin and that
In
this was also the source of the abnormal cells. I do not know of any way to investigate this possibility. The illustrations of thymus from a
pregnant guinea pig purporting
to
eosinophilic globules are unconvincing. Dr Simmon's argument that globules rather than red blood cells were seen might be more persuasive show
if illustrations of human leukemic cells had been provided. I have never observed such globules in leukemic cells that could be mistaken for erythrocytes. Furthermore, the illustrations in the original report were of malignant histiocytes in the bone
of some cells seen in Fig 1. The glo¬ bules show retained secretion within thymic plasma cells (origi¬ nal magnification x 500) (from Simmons').
Fig 2.—Higher magnification
Downloaded From: http://jama.jamanetwork.com/ by a Florida International University Medical Library User on 06/10/2015
as space permits and at the discretion of the editor. They should be typewritten triple-spaced, with five or fewer references, should not exceed two pages in length, and will be subject to editing. Letters
are
not
acknowledged.
Propoxyphene Overdose Deaths To the Editor.\p=m-\Weare observing an alarming increase in North Carolina
in the number of deaths attributable to propoxyphene. We doubt that the phenomenon is peculiar to this state. Most physicians may not be aware of the problem, in spite of the article in
by Sturner and Garriott (223:1125, 1973). This state's Medical Examiner Sys-
THE JOURNAL
tem detected 21 deaths in 1972 and 21 in 1973 attributable to propoxyphene.
Thirteen such deaths were identified in the first half of 1974, and 17 more in the last half of that year. In the first three months of 1975, sixteen more deaths have been recorded. In comparison, there has been an average of 39 barbiturate deaths annually from 1971 to 1974. There have been only three barbiturate deaths during the first quarter of this year, when there were 16 propoxyphene deaths. Most of the propoxyphene deaths have been suicidal overdoses; some have been accidents. Propoxyphene is a prescription analgesic second only to aspirin in popu¬ larity. The drug in the various forms of Darvon was the most commonly
in 1972. Although Darvon is the most widely used pro¬ poxyphene, it is also available as Dolene, Pro-Gesic-65, and SK-65. The relatively new napsylate salt of pro¬ poxyphene, Darvon-N, is reputed to be safer than hydrochloride salt be¬ cause of its poor solubility. We are unaware that one form of propoxy¬ phene is demonstrably safer than an¬ other. We offer several possibilities to ac¬ count for the increase in recognized propoxyphene deaths: (1) the resched¬ uling-induced decrease in availabil¬
prescribed drug
of rapid-acting barbiturates, (2) stricter controls on the much less le¬ thal analgesic codeine; (3) the mis¬ conception among many physicians that propoxyphene is essentially harmless; and (4) the situation that Medicare will pay for propoxyphene
ity
Edited
by John
D.
Archer, MD, Senior Editor.
prescriptions aspirin.
but will not pay for
Communities that
are
not detect¬
ing propoxyphene deaths may not have adequate death investigative systems including competent tox¬ icology facilities. Recent improve¬ ment in techniques may account for discovery of cases that would other¬
wise have gone undetected.1 It is our opinion that 15 to 20 of the 65-mg capsules (or of the 100-mg napsylate salt compressed tablets) may cause death, and that somewhat lesser amounts may do so with ethanol or other central nervous system depres¬ sants. In our experience, blood con¬ centrations of propoxyphene together with other depressants that exceed 0.1 mg/100 ml, and of propoxyphene alone that exceed 0.2 mg/100 ml, can cause death. Arthur J. McBay, PhD Page Hudson, MD Office of the Chief Medical Examiner Chapel Hill, NC 1. McBay AJ, Turk RF, Corbett BW, et al: Determination of propoxyphene in biological materials. J Forensic Sci 19:81-89, 1974.
Axillary Hyperhidrosis To the Editor.\p=m-\We were pleased to note the success Andersen and his col-
leagues (231:1026, 1975) have had in treating axillary hyperhidrosis in more than 250 patients by the employment of the simple surgical technique we introduced in 1963.
Although Andersen states that cur-
"topical treatment of hyperhidrosis of the axillae is, nine times out of ten, ineffective," we would like to record that we have now discovered a topical antiperspirant system that is even more effective than our simple surgical procedure. Although the method was initially outlined last year,1 it is fully detailed in a forthcoming article.2 In essence, complete axillary anhirent
drosis, as demonstrated by sustained garment armpit dryness, could regu-
larly be achieved in hyperhidrotic patients within 48 hours by the following trinary technique: (1) local application of 20% aluminum chloride
hexahydrate in anhydrous ethyl alcohol (200-proof); (2) making this application on the dry, unwashed, nonsweating axilla at the time of re¬ tiring; and (3) covering the treated area for the subsequent six to eight hours with a thin, water vapor-imper¬ meable plastic film such as vinyl chloride-vinylidine chloride copolymer sheeting (Saran Wrap). The plastic film must be kept in snug apposition to the skin by a dress-shield garment or by a well-fitted body shirt. On aris¬ ing, the patient removes the plastic film and washes the area. Subsequent application with this technique once weekly maintains the anhidrosis in¬ definitely. Walter B. Shelley, MD Harry J. Hurley, Jr, MD
Philadelphia
Shelley WB: Consultations in Dermatology II. Philadelphia, WB Saunders Co, 1974, pp 256-262. 2. Shelley WB, Hurley HJ: Studies on topical antiperspirant control of axillary hyperhidrosis. Acta Derm Venereol, to be published. 1.
Phencyclidine Poisoning To the Editor.\p=m-\Intheir article, "Hypertensive Crisis and Death Associated With Phencyclidine Poisoning" (231:1270, 1975), Eastman and Cohen attributed the death of their patient to "a direct result of the pressor ef-
fect of the drug" phencyclidine, even the acute hypertensive episode occurred three days following ingestion of the agent, at which time there was no phencyclidine detectable in his blood or urine. On that date the patient was described as "drowsy"; dilated pupils and rigidity developed, while his blood pressure was normal (140/90 mm Hg). He then became comatose, and hypertension (220/130
though
mm
Hg) and respiratory arrest devel-
He never regained consciousand died four days later. On the basis of this sequence of events, it appears that the neurological abnormalities developed before the patient be-
oped. ness
came
hypertensive.
An alternative explanation to the pathophysiology described by the authors is that the patient suffered from residual central nervous system depressant effects of the phencyclidine or from some other agent taken prior to or during his hospitalization. The resultant respiratory depression or airway obstruction or both produced acute hypoxemia with catecholamine release and its attendant finding, hy¬ pertension, causing the intracerebral hemorrhage noted on postmortem ex¬ amination. Thus, the hypertensive episode may have been the result,
Downloaded From: http://jama.jamanetwork.com/ by a Florida International University Medical Library User on 06/10/2015
rather than the cause, of the patient's neurological dysfunction. It may not be correct, therefore, to attribute this individual's death directly to the pressor effect of phencyclidine.
1. Serck-Hansen A, Purchit GP: Histiocytic medullary reticulosis. Br J Cancer 22:506-516, 1968. 2. Amsel S, Bijlsma F: Histiocytic medullary reticulosis. Trop Geogr Med 26:31-38, 1974. 3. Cline MJ, Golde DW: A review and reevaluation of histiocytic disorders. Am J Med 55:49, 1973.
Robert H. Libman, MD Illinois Masonic Medical Center
To the Editor \p=m-\DrDavid Shreiner's article was very interesting and has stimulated me to make the follow-
Chicago
Acute Lymphoblastic Leukemia And Histiocytic
Medullary Reticulocytosis
To the Editor.\p=m-\DrShreiner's article
(231:838, 1975) suggests a stem-cell abnormality as the possible underlying cause of the patient's acute
lymphoblastic leukemia and subsequent histiocytic medullary reticulosis. Further thought on the cause of the latter disease is provoked by the
existence of 25 cases of histiocytic medullary reticulosis seen at Mulago
Hospital in Uganda over a seven-year period.1-2 Good American articles often fail
to note the existence of this large number of cases.3 Serck-Hansen and Purchit have postulated that the increased incidence of cases in the tropics may be due to increased stimulation of the reticuloendothelial system, resulting from frequent infections or from malnutrition beginning in early infancy.1 It may be of additional interest that many of these cases come from the same area where there is an increased incidence of Burkitt lym-
phoma.
Robert F. Marvin, MD Drexel Hill, Pa
Fig are
ing
comments. The chest roentgenogram showed
an anterosuperior mediastinal mass that varied in size from time to time. The nature of the mass and its origin were not defined except to indicate that the mass was composed of malignant histiocytes. I suggest that the mass may have been of thymic origin and that it was the source of the abnormal cells, rather than a depository for them.1-3 The illustrations of "erythrophagocytosis" may represent such a phenomenon, but I call attention to the possibility that the globules may not be red blood cells at all, but retained
phagocytosed glycoprotein globules secreted by these cells or others of the plasma cell line. The similarity of such globules to red blood cells has often deceived me and confused many other investigaor
one is aware illustrated in the phenomenon accompanying photographs, he will make assumptions that are unwar¬ ranted, without feeling the need to double-check the identity of forms that appear quite obviously to be
tors in the
of the
past. Unless
erythrocytes.
When the cells illustrated in
1 .—Section of thymus from pregnant guinea pig. The globules eosinophilic and resemble erythrocytes (original magnifica¬
tion x
200) (from Simmons3).
Fig
1
and 2 are present in large numbers in the spleen, it requires an awareness of their presence plus very careful ex¬ amination to distinguish them from red blood cells, which may be adjacent to, above, and beneath them. If, in fact, the globules described by Dr Shreiner were not red blood cells at all, it would be less "surprising that the reticuloendothelial scan showed a great decrease in the reticu¬ loendothelial activity of the bone marrow." Vaughan P. Simmons, MD
Philadelphia 1. Simmons VP:
atrics
Thymic
function and leukemia. Pedi-
5:574-595, 1950.
diseases, globulins, plasma cells, Russell bodies, Foa-Kurloff bodies, and the thymus: A unifying concept. Wis Med J 66:349-364, 1967. 3. Simmons VP: The thymus comes to age. Trans Assoc Life Ins Med Dir Am 57:86-122, 1973. 2. Simmons VP: Diverse
Reply.\p=m-\DrSimmons may be quite right that the mediastinal mass may have been of thymic origin and that
In
this was also the source of the abnormal cells. I do not know of any way to investigate this possibility. The illustrations of thymus from a
pregnant guinea pig purporting
to
eosinophilic globules are unconvincing. Dr Simmon's argument that globules rather than red blood cells were seen might be more persuasive show
if illustrations of human leukemic cells had been provided. I have never observed such globules in leukemic cells that could be mistaken for erythrocytes. Furthermore, the illustrations in the original report were of malignant histiocytes in the bone
of some cells seen in Fig 1. The glo¬ bules show retained secretion within thymic plasma cells (origi¬ nal magnification x 500) (from Simmons').
Fig 2.—Higher magnification
Downloaded From: http://jama.jamanetwork.com/ by a Florida International University Medical Library User on 06/10/2015
