vitamin-treated group is obvious. Data from each group were pooled since no dose-response effect was
apparent.
Let Them Eat Catfish To the Editor.\p=m-\Historyteaches that scientists are inclined to eat carcasses of test animals. Indeed, a well-known double-doctorate space scientist dined frequently on rats during his salad days. A group on the Eastern seaboard eats exotic animals at their annual banquets. Even nonscientists do it. For example, a sparring Southern editor and his cocky Governor had an election bet in which the loser would eat a crow at a specified banquet. He did and when asked how it tasted said, "Well, it tasted a lot like owl." The Scoggin (231:176, 1975) report on catfish stings is noteworthy because it shows that research is needed to identify this toxin. To achieve this goal, some interested soul will have to brave the elements to catch some study specimens. Then he'll have to remove the dorsal and pectoral fin spines for scientific purposes. I hope he knows what to do with the rest of the critters. Henry C. Caldwell, PhD
Philadelphia
Contamination in Open Heart
Surgery
To the Editor.\p=m-\In the article "Sources of Contamination in Open Heart Surgery" (230:1415, 1974), Kluge et al reported a 71% incidence of positive cultures from various sites during the operative procedure. When discussing possible sources for the microorganisms the authors overlooked one hidden but well-known source, the anesthetic gas machine. Morbidity and mortality due to infection acquired from anesthetic breathing circuits in patients undergoing open heart surgery has been reported previously.1,2 In both of these outbreaks the offending bacteria were strains of Pseudomonas aeruginosa. Respiratory tract colonization, infection, and septicemia occurred in two groups of patients undergoing open heart surgery. Phage typing allowed presumptive linkage of exposure to contaminated anesthetic equipment and subsequent infection. Both epiEdited
by John D. Archer, MD,
demics abruptly terminated on the introduction of proper sterilization procedures for the anesthetic circuits. Douglas B. Craig, MD
Winnipeg, Manitoba 1. Tinne JE, Gordon AM, Bain WH, et al: Cross-infection by Pseudomonas aeruginosa as a hazard of intensive surgery. Br Med J 4:313-315, 1967. 2. Olds JW, Kish AL, Eberle BJ, et al: Pseudomonas aeruginosa respiratory tract infection acquired from a contaminated anesthesia machine. Am Rev Resp Dis 105:628-632, 1972.
Coagulopathy
and Fat-Soluble Vitamins To the
Editor.\p=m-\Therecent report by Corrigan and Marcus describing
potentiation of warfarin anticoagulation by vitamin E (230:1300, 1974) is consistent with some unpublished studies performed several years ago by Dr. H. M. Solomon and myself. We conducted preliminary
studies of the effect of vitamins A, D, and E on vitamin K-dependent clotting factor activity as measured by the anticoagulant response to single doses of warfarin or dicumarol. Briefly, male rats were given warfarin before and after four days' treatment with one of the following: vitamin A acetate, 1,000-15,000 international units (IU); ergocalciferol, 404,000 IU; vitamin E, 0.7-70 IU. The Figure shows the distribution of percent of coagulation activity found 72 hours after warfarin administration in treated and control groups. Potentiation of anticoagulant effect in each
Senior Editor.
Downloaded From: http://jama.jamanetwork.com/ by a Thomas Jefferson University User on 05/14/2015
Subsequently, three healthy human volunteers were given vitamin E, 42 IU/day for 30 days, and the effect of dicumarol, 150 mg, was measured be¬ fore and at the conclusion of the treatment period. Mean prothrombin activity at 36 hours decreased from 52% during the control period to 33% at the end of the study period. Similar results were obtained in three other volunteers given vitamin A, 25,000 IU for 30 days. No effects of the treat¬ ments on plasma half-life of anti¬ coagulant drug were observed. Our conclusions were that signifi¬ cant antagonistic effects of vitamin A, D, and E on vitamin K-dependent
clotting activity
were
demonstrated
in rats, but that these were of doubt¬ ful clinical significance at the doses tested. However, as the report of Cor¬ rigan and Marcus suggests, much higher doses of vitamin E in man, es¬ pecially given in conjunction with an¬ other potentiator of anticoagulants,
clofibrate, may produce more extreme effects. Thus, the status of vitamin A,
D, and E nutrition must be added to the list of factors to be considered in the evaluation of suspected anti¬
coagulant drug interactions.
John J. Schrogie, MD
Ridgewood,
NJ
Hormone
Exposure and Lymphocytic Impairment
To the Editor.\p=m-\I was interested to read Dr. Ablin's recent letter "Diethylstilbestrol Exposure and
Lymphocytic Impairment" (229:1863, 1974). In our own studies,1 implanted HeLa tumors in estrogen-treated female mice survived longer than those
in untreated control mice. Furthermore, these mice experienced a
profound lymphopenia. Although
a
less marked lymphopenia also occurred in estrogen-treated male mice, HeLa tumors in such mice regressed before those in control mice did. Androgen treatment of female mice, on the other hand, resulted in a rapid lymphocytosis, and there was regression of HeLa tumors before similar tumors regressed in control mice. In male mice, androgen produced a marked and lasting lymphopenia. HeLa tumors in such mice survived beyond those in controls. In all these studies, a non-hormone-
dependent tumor was used, and yet it possible to influence the growth
was
of tumors. The evidence would appear to suggest there has been a change in cell-mediated immunity, concurrent with the observed changes in lymphocyte count. Only then can one account for the different survival of tumors in our hormone-treated mice. In the in vitro studies, estrogen and
androgen acts preferentially against lymphocytes from female and male mice, respectively, after only ten min¬ utes incubation, the response being assessed on the basis of lymphocyte kill. Although only a few normal hu¬ man subjects have been studied to date, this preference of estrogen for lymphocytes from females, and an¬ drogen for lymphocytes from males, is even more marked. No explanation can be offered for this selectivity. As far as the in vivo findings in mice are concerned, the crux of the matter is whether these also occur in patients with breast cancer who receive hormone treatment. At the present time, a study is in progress. C. R. Franks, MB, BS London
blurred vision, for which her present lenses longer corrective, many dental caries and poor oral hygiene, severe vulvar pruritis, and a weight loss of 8.1 kg (18 lb) over the past two months. In addition, some five years earlier (one year before on¬ set of diabetes), she had noticed asympto¬ matic puffmess in her cheeks. The patient was a poorly nourished, ade¬ quately developed, hydrated, asthénie woman in no acute distress. Examination of the head and neck revealed bilaterally enlarged, nontender parotid glands. The patient's condition was evaluated and ap¬ propriate therapy for her diabetes was ef¬ fected. Evidence for liver disease or vita¬ min deficiencies was sought but not found. were no
Sialograms
were
not
performed.
Comment.—Asymptomatic enlarge¬ parotid glands has been
ment of the
cited in association with a number of diseases. Besides Mikulicz/Heerfordt syndrome and Sjogren syndrome, the following are worthy of mention: (1) cirrhosis of the liver, (2) pellagra, (3) chronic malnutrition, (4) vitamin A deficiency, (5) lead intoxication, (6) thiouracil therapy, and (7) chronic Chagas disease. Evidence for none of these, however, was found in this
patient.
Parotid
enlargement also occurs infrequently with diabetes mel¬ litus and may even precede the clini¬ cal onset of the disease, as noted by
CR, Perkins FT, Bishop D: The effect of sex hormones on the growth of HeLa tumours in male and female mice. Br J Cancer 31:100-110, 1975.
not
Asymptomatic Parotid Enlargement: Probable Diabetic Origin
Davidson et al.1 In fact, the incidence of parotid enlargement coinciding with diabetes mellitus discovered on physical examination is highly clini¬
1. Franks
To the Editor.\p=m-\The
appearance of
asymptomatic, bilateral parotid enlargement is widely recognized as a relatively frequent clinical occurrence.
It has been noted in Mikulicz
syndrome associated with sarcoidosis, in Reiter syndrome, and in several other disorders. However, it is not generally appreciated that this interesting physical finding can also be associated with diabetes mellitus.
Report of a Case.\p=m-\A 50-year-old woman's condition was first diagnosed as adult-onset diabetes mellitus at age 46. After evaluation at another hospital, she was placed on an American Diabetes Association diet and a daily dose of approximately 100 mg of tolbutamide. During the succeeding four years, the patient demonstrated poor diabetic control on numerous occasions and was eventually switched to tolazamide, 500 mg daily. On the day of admission to our hospital, the patient was complaining of dizziness, weakness, and faintness. She gave a history of diabetes, and a blood glucose level determined at that time was 520 mg/100 ml. Further history disclosed recent onset of
cally important. Yet, surprisingly enough, there is but scant mention of
it in the literature. On examination of this particular pa¬ tient, her parotid swelling was first thought to be a separate disease pro¬ cess from diabetes mellitus. Since it was asymptomatic, the status not having changed for five years, this problem was given a low priority. However, after review of the perti¬ nent literature, it was concluded that this case was decidedly similar to those previously reported by David¬ son et al1 and Shroff et al- and was
probably due solely
to diabetes mellitus. Davidson et al1 studied 14 patients with diabetes mellitus and asympto¬ matic parotid enlargement. In five of the patients, the parotid enlargement preceded the onset of clinically mani¬ fest diabetes, and only by glucose tol¬ erance tests was the diagnosis of dia¬ betes established. Shroff et al2 studied 100 cases of di¬ abetes. Of these, a surprisingly high 53% had asymptomatic, bilaterally
Downloaded From: http://jama.jamanetwork.com/ by a Thomas Jefferson University User on 05/14/2015
enlarged parotid glands. Thirty-six of these patients were between the ages of 41 and 60 years (there was no sta¬ tistically significant difference in fre¬ quency of appearance of parotid en¬ largement based on sex).
The case studied here conforms well to the characteristics delineated by these authors: (1) the onset of pa¬ rotid swelling preceded the onset of clinically manifest diabetes, and (2) it appeared somewhere between the fourth and sixth decades. In conclusion, when a patient has an isolated finding of asymptomatic, bilateral parotid enlargement, it ap¬ pears from the material cited previ¬ ously that a glucose tolerance test in an effort to establish an early diag¬ nosis of diabetes mellitus is well
justified. David E. Silverman New York 1. Davidson
D, Leibel BS, Berris B: Asymptomatic pagland enlargement in diabetes mellitus. Ann InMed tern 70:31-39, 1969. 2. Shroff DF, Modi TH, Rajkondawar VL: Asymptomatic bilateral parotid gland enlargement in diabetes rotid
mellitus
(preliminary communication). J
cians India 20:251-254, 1972.
Assoc
Physi-
Intravenous Catheter for Thoracentesis and Pericardiocentesis To the Editor.\p=m-\Needlethoracentesis high risk of iatrogenically produced pneumothorax caused by puncture of the expanding lung. As a thoracic surgeon, I am all too frequently called on to insert a chest tube to expand the collapsed lung. This problem can be almost completely eliminated by using the commercially available intravenous catheter (Bardic 1814R inside needle catheter with stylet; needle gauge, 14; catheter length, 30.5 cm) or its runs a
equivalent, attached to stopcock and syringe.
a
three-way
Once the catheter has been intro-
duced, the danger of puncturing the underlying lung is eliminated. The patient need not be immobile or fear to cough. Aspiration is more thorough. Medication such as quinacrine (Atabrine) hydrochloride can be in-
troduced with ease. The physician is more comfortable. This technique has been applied to pericardiocentesis,1 with the same salutary results, so as to avoid lacerating the heart. Paul A. Kirschner, MD New York
1. Kirschner
PA, Wisoff BG: Use of intravenous cathefor pericardiocentesis and thoracentesis. J Mt Sinai vol No. 31, 5, September 1964. Hosp, ter
apparent.
Let Them Eat Catfish To the Editor.\p=m-\Historyteaches that scientists are inclined to eat carcasses of test animals. Indeed, a well-known double-doctorate space scientist dined frequently on rats during his salad days. A group on the Eastern seaboard eats exotic animals at their annual banquets. Even nonscientists do it. For example, a sparring Southern editor and his cocky Governor had an election bet in which the loser would eat a crow at a specified banquet. He did and when asked how it tasted said, "Well, it tasted a lot like owl." The Scoggin (231:176, 1975) report on catfish stings is noteworthy because it shows that research is needed to identify this toxin. To achieve this goal, some interested soul will have to brave the elements to catch some study specimens. Then he'll have to remove the dorsal and pectoral fin spines for scientific purposes. I hope he knows what to do with the rest of the critters. Henry C. Caldwell, PhD
Philadelphia
Contamination in Open Heart
Surgery
To the Editor.\p=m-\In the article "Sources of Contamination in Open Heart Surgery" (230:1415, 1974), Kluge et al reported a 71% incidence of positive cultures from various sites during the operative procedure. When discussing possible sources for the microorganisms the authors overlooked one hidden but well-known source, the anesthetic gas machine. Morbidity and mortality due to infection acquired from anesthetic breathing circuits in patients undergoing open heart surgery has been reported previously.1,2 In both of these outbreaks the offending bacteria were strains of Pseudomonas aeruginosa. Respiratory tract colonization, infection, and septicemia occurred in two groups of patients undergoing open heart surgery. Phage typing allowed presumptive linkage of exposure to contaminated anesthetic equipment and subsequent infection. Both epiEdited
by John D. Archer, MD,
demics abruptly terminated on the introduction of proper sterilization procedures for the anesthetic circuits. Douglas B. Craig, MD
Winnipeg, Manitoba 1. Tinne JE, Gordon AM, Bain WH, et al: Cross-infection by Pseudomonas aeruginosa as a hazard of intensive surgery. Br Med J 4:313-315, 1967. 2. Olds JW, Kish AL, Eberle BJ, et al: Pseudomonas aeruginosa respiratory tract infection acquired from a contaminated anesthesia machine. Am Rev Resp Dis 105:628-632, 1972.
Coagulopathy
and Fat-Soluble Vitamins To the
Editor.\p=m-\Therecent report by Corrigan and Marcus describing
potentiation of warfarin anticoagulation by vitamin E (230:1300, 1974) is consistent with some unpublished studies performed several years ago by Dr. H. M. Solomon and myself. We conducted preliminary
studies of the effect of vitamins A, D, and E on vitamin K-dependent clotting factor activity as measured by the anticoagulant response to single doses of warfarin or dicumarol. Briefly, male rats were given warfarin before and after four days' treatment with one of the following: vitamin A acetate, 1,000-15,000 international units (IU); ergocalciferol, 404,000 IU; vitamin E, 0.7-70 IU. The Figure shows the distribution of percent of coagulation activity found 72 hours after warfarin administration in treated and control groups. Potentiation of anticoagulant effect in each
Senior Editor.
Downloaded From: http://jama.jamanetwork.com/ by a Thomas Jefferson University User on 05/14/2015
Subsequently, three healthy human volunteers were given vitamin E, 42 IU/day for 30 days, and the effect of dicumarol, 150 mg, was measured be¬ fore and at the conclusion of the treatment period. Mean prothrombin activity at 36 hours decreased from 52% during the control period to 33% at the end of the study period. Similar results were obtained in three other volunteers given vitamin A, 25,000 IU for 30 days. No effects of the treat¬ ments on plasma half-life of anti¬ coagulant drug were observed. Our conclusions were that signifi¬ cant antagonistic effects of vitamin A, D, and E on vitamin K-dependent
clotting activity
were
demonstrated
in rats, but that these were of doubt¬ ful clinical significance at the doses tested. However, as the report of Cor¬ rigan and Marcus suggests, much higher doses of vitamin E in man, es¬ pecially given in conjunction with an¬ other potentiator of anticoagulants,
clofibrate, may produce more extreme effects. Thus, the status of vitamin A,
D, and E nutrition must be added to the list of factors to be considered in the evaluation of suspected anti¬
coagulant drug interactions.
John J. Schrogie, MD
Ridgewood,
NJ
Hormone
Exposure and Lymphocytic Impairment
To the Editor.\p=m-\I was interested to read Dr. Ablin's recent letter "Diethylstilbestrol Exposure and
Lymphocytic Impairment" (229:1863, 1974). In our own studies,1 implanted HeLa tumors in estrogen-treated female mice survived longer than those
in untreated control mice. Furthermore, these mice experienced a
profound lymphopenia. Although
a
less marked lymphopenia also occurred in estrogen-treated male mice, HeLa tumors in such mice regressed before those in control mice did. Androgen treatment of female mice, on the other hand, resulted in a rapid lymphocytosis, and there was regression of HeLa tumors before similar tumors regressed in control mice. In male mice, androgen produced a marked and lasting lymphopenia. HeLa tumors in such mice survived beyond those in controls. In all these studies, a non-hormone-
dependent tumor was used, and yet it possible to influence the growth
was
of tumors. The evidence would appear to suggest there has been a change in cell-mediated immunity, concurrent with the observed changes in lymphocyte count. Only then can one account for the different survival of tumors in our hormone-treated mice. In the in vitro studies, estrogen and
androgen acts preferentially against lymphocytes from female and male mice, respectively, after only ten min¬ utes incubation, the response being assessed on the basis of lymphocyte kill. Although only a few normal hu¬ man subjects have been studied to date, this preference of estrogen for lymphocytes from females, and an¬ drogen for lymphocytes from males, is even more marked. No explanation can be offered for this selectivity. As far as the in vivo findings in mice are concerned, the crux of the matter is whether these also occur in patients with breast cancer who receive hormone treatment. At the present time, a study is in progress. C. R. Franks, MB, BS London
blurred vision, for which her present lenses longer corrective, many dental caries and poor oral hygiene, severe vulvar pruritis, and a weight loss of 8.1 kg (18 lb) over the past two months. In addition, some five years earlier (one year before on¬ set of diabetes), she had noticed asympto¬ matic puffmess in her cheeks. The patient was a poorly nourished, ade¬ quately developed, hydrated, asthénie woman in no acute distress. Examination of the head and neck revealed bilaterally enlarged, nontender parotid glands. The patient's condition was evaluated and ap¬ propriate therapy for her diabetes was ef¬ fected. Evidence for liver disease or vita¬ min deficiencies was sought but not found. were no
Sialograms
were
not
performed.
Comment.—Asymptomatic enlarge¬ parotid glands has been
ment of the
cited in association with a number of diseases. Besides Mikulicz/Heerfordt syndrome and Sjogren syndrome, the following are worthy of mention: (1) cirrhosis of the liver, (2) pellagra, (3) chronic malnutrition, (4) vitamin A deficiency, (5) lead intoxication, (6) thiouracil therapy, and (7) chronic Chagas disease. Evidence for none of these, however, was found in this
patient.
Parotid
enlargement also occurs infrequently with diabetes mel¬ litus and may even precede the clini¬ cal onset of the disease, as noted by
CR, Perkins FT, Bishop D: The effect of sex hormones on the growth of HeLa tumours in male and female mice. Br J Cancer 31:100-110, 1975.
not
Asymptomatic Parotid Enlargement: Probable Diabetic Origin
Davidson et al.1 In fact, the incidence of parotid enlargement coinciding with diabetes mellitus discovered on physical examination is highly clini¬
1. Franks
To the Editor.\p=m-\The
appearance of
asymptomatic, bilateral parotid enlargement is widely recognized as a relatively frequent clinical occurrence.
It has been noted in Mikulicz
syndrome associated with sarcoidosis, in Reiter syndrome, and in several other disorders. However, it is not generally appreciated that this interesting physical finding can also be associated with diabetes mellitus.
Report of a Case.\p=m-\A 50-year-old woman's condition was first diagnosed as adult-onset diabetes mellitus at age 46. After evaluation at another hospital, she was placed on an American Diabetes Association diet and a daily dose of approximately 100 mg of tolbutamide. During the succeeding four years, the patient demonstrated poor diabetic control on numerous occasions and was eventually switched to tolazamide, 500 mg daily. On the day of admission to our hospital, the patient was complaining of dizziness, weakness, and faintness. She gave a history of diabetes, and a blood glucose level determined at that time was 520 mg/100 ml. Further history disclosed recent onset of
cally important. Yet, surprisingly enough, there is but scant mention of
it in the literature. On examination of this particular pa¬ tient, her parotid swelling was first thought to be a separate disease pro¬ cess from diabetes mellitus. Since it was asymptomatic, the status not having changed for five years, this problem was given a low priority. However, after review of the perti¬ nent literature, it was concluded that this case was decidedly similar to those previously reported by David¬ son et al1 and Shroff et al- and was
probably due solely
to diabetes mellitus. Davidson et al1 studied 14 patients with diabetes mellitus and asympto¬ matic parotid enlargement. In five of the patients, the parotid enlargement preceded the onset of clinically mani¬ fest diabetes, and only by glucose tol¬ erance tests was the diagnosis of dia¬ betes established. Shroff et al2 studied 100 cases of di¬ abetes. Of these, a surprisingly high 53% had asymptomatic, bilaterally
Downloaded From: http://jama.jamanetwork.com/ by a Thomas Jefferson University User on 05/14/2015
enlarged parotid glands. Thirty-six of these patients were between the ages of 41 and 60 years (there was no sta¬ tistically significant difference in fre¬ quency of appearance of parotid en¬ largement based on sex).
The case studied here conforms well to the characteristics delineated by these authors: (1) the onset of pa¬ rotid swelling preceded the onset of clinically manifest diabetes, and (2) it appeared somewhere between the fourth and sixth decades. In conclusion, when a patient has an isolated finding of asymptomatic, bilateral parotid enlargement, it ap¬ pears from the material cited previ¬ ously that a glucose tolerance test in an effort to establish an early diag¬ nosis of diabetes mellitus is well
justified. David E. Silverman New York 1. Davidson
D, Leibel BS, Berris B: Asymptomatic pagland enlargement in diabetes mellitus. Ann InMed tern 70:31-39, 1969. 2. Shroff DF, Modi TH, Rajkondawar VL: Asymptomatic bilateral parotid gland enlargement in diabetes rotid
mellitus
(preliminary communication). J
cians India 20:251-254, 1972.
Assoc
Physi-
Intravenous Catheter for Thoracentesis and Pericardiocentesis To the Editor.\p=m-\Needlethoracentesis high risk of iatrogenically produced pneumothorax caused by puncture of the expanding lung. As a thoracic surgeon, I am all too frequently called on to insert a chest tube to expand the collapsed lung. This problem can be almost completely eliminated by using the commercially available intravenous catheter (Bardic 1814R inside needle catheter with stylet; needle gauge, 14; catheter length, 30.5 cm) or its runs a
equivalent, attached to stopcock and syringe.
a
three-way
Once the catheter has been intro-
duced, the danger of puncturing the underlying lung is eliminated. The patient need not be immobile or fear to cough. Aspiration is more thorough. Medication such as quinacrine (Atabrine) hydrochloride can be in-
troduced with ease. The physician is more comfortable. This technique has been applied to pericardiocentesis,1 with the same salutary results, so as to avoid lacerating the heart. Paul A. Kirschner, MD New York
1. Kirschner
PA, Wisoff BG: Use of intravenous cathefor pericardiocentesis and thoracentesis. J Mt Sinai vol No. 31, 5, September 1964. Hosp, ter
