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Studies of the autonomic nervous system in “atopic” individuals
STUDIES
STANLEY
OF THE
COHEN,
M.D.,
AUTONOMIC NERVOUS INDIVIDUALS*
AND
HORACE
L. WOLF,
SYSTEM
B.S.,
M.D.,
IN
NEW
L’ATOPLC”‘
ORLEANS.
IJA.
T
HE importance of hypersensitivity in hay fever and bronchial asthma is well recognized. However, it is a common observation that the majority of attacks of bronchial asthma cannot be explained by recent or increased contact with An outstanding example of substances to which the patient is hypersensitive. this is the part meteorologic disturbances play in the production of attacks in patients who are hypersensitive to environmental allergens which they contacdt the year around. There is little doubt that mechanisms which do not involve an antigen-antibody reaction contribute mat,erially to the clinical production of the attack. Little is known concerning these mechanisms. Several studies have been made on the disturbance of water and electrolyte balance in this disease.l-” These studies clearly indicate that these factors influence the occurrence of allergic l)henomena. The importance of emotional factors in the precipitation 0 allergic reactions is likewise well recognized. French and Alexander4 point out! that the psychogenic factor of fear of separation or estrangement from some mother figure tends to precipitate asthmatic attacks. ,\ccording to those authors, ill such a situation the asthmatic attacks seem to ha,rc the significance of a suppressed cry. The finding of an increased incidence in the dominant alpha type of electroencephalogram in asthmatic patients by Rubin and Moses5 is additional evidence of the importance of the nervous system in this disease. It, is quite possible that many of these nonspeoific, yet important causes of allergic upsets are mediated through the autonomic nervous system. KunW quite aptly calls attention to t,he evidence for autonomic imbalance ill allc~*g!~ disease. Vasodilatation occurring in the mucous membranes as a result nt’ cholinergic stimulation permit,s increased permeabilit,y of the capillary bed with tissue edema and the substratum for increased secretory output of the mucous glands. To quote Knntz, “ Some of the most, characteristic manifestations of allergic disease, therefore, are calrsally ~la~e(l to Iwightened parasympathetic or’ cholinergic reactivity.” With those ideas in mind, we decided to compare palmsr sweating of allergic and nonallergic patients. Sweat glands are supplied bp fibers of the sympatheiic *From the sity of Louisiana, Touro Infirmary.
Department Allergy
of Preventive Medicine, School of Clinic, Hutchinson Memorial Clinic
391
Medicine, and the
The Tulane Division of
UnivcrAllergy.
392
THE
JOURNAL
OF
ALLERGY
nervous system, but functionally they are cholinergic. Palmar sweating bears no relationship to water loss from other parts of the skin or respiratory tract. However, it occurs wit.h relative independence of environmental temperature, is continuous during waking hours and is influenced by emotional stimuli.’ PROCEDURE
Three groups of patients were studied. No individuals below 15 years or above 65 years of age were included. Members of both sexes and the white and Negro races were examined without selection. The first group consisted of 63 patients with allergic respiratory disease. The diagnosis in each case was made clinically and substantiated by secretion or blood eosinophilia in some cases, and positive skin tests in all cases. About three-fourths of those patients had sustained clear-cut attacks of bronchial asthma. Where anxiety was apparent, as manifested by palpitation, tremor, tenseness, weakness, dilated pupils, sleep disturbances, or psychological phenomena of a defensive nature, such as conversion symptoms or phobias existed, the patient was excluded from this group. This was an uncommon occurrence. The second group consisted of 63 psychoneurotic patients from the neuropsychiatric service of Touro Infirmary. These patients were studied as they returned for routine visits. None with overt organic nervous system disease, psychoses, syphilis, or allergic disease were included. This group was studied in order to assess the psychiatric factor in palmar sweating in the clinic group of patients. The third group of 99 syphilitic patients was selected because they presented an analagous situation in the clinic to the allergic group. These patients were all awaiting injections of mapharsen or bismuth. Thus, they afforded a comparison to the allergic patients, the majority of whom also were anticipating parenteral medication. Patients with overt nervous system, circulatory, or allergic disea,se were excluded from this group. The method used to measure palmar sweating was that of Silverman and PowelLs Briefly, it consists of the application of an alcoholic solution of ferric chloride to the palm. The alcohol is allowed to evaporate. The palm is exposed for a standard time to a paper impregnated with tannic acid. The intensity of the ink produced on the paper is proporti0nat.e to the amount of sweat liberated from the palm. All patients were studied during their routine visits to the clinic, No patient was studied during or immediately following a spell of asthma or a dose of epinephrine or ephedrine. However, all were studied at a time of the year (spring) TABLE DEGREE
OF
RESPONSE
-T 1:: IV Total Percentage
III
and
IV
I
ALLERGIC
I I-
PSYCHONEUROTIC
1
SYPHILITIC
28
31
50
149 12
195
n59
5 63
5 99
20
14
63 41
COHEN
:
AUTONOMIC
when allergic upsets are common cording to the method advocated intense reactions (Table I). All purposes of comparison, Groups compared to Groups III and IV TABLE
II.
COMPARISON
NERVOUS
393
STSTl$XI
in New Orleans, The papers were graded, acby Silverman, into four gl’onps: from mild to records were read at the same sitting. For I and II (negative intense sweaters) w(tt’(’ (positive intense sweaters) (Table II).
0% THE
OBSERVATIONS
&PHII,ITIC
AND
AND
PSY~IIO~~EUR~TIC
GIWW
ANALYSIS
The incidence of intense palmar sweating was found to be 41 per cent, in the allergic group, 20 per cent in the psychoneurotic group, and 14 PCV cent in the syphilitic group. The chi square statistic (Brandt-Snedecor formula” ) was ~~scti to c:ll(A~~ht~: probability, and the psychoneurotic and syphilitic groups of patient,s were cornpared for significant differences. By this method. chi square = 1.17 n-l (one degree of freedom) p = 0.20-0.30 This high value of p indicates that there is no significant difference in the incidence of intense palmar sweating in patients with syphilitic and psychoneurotic disease, both being nonallergic. We may, therefore, use both groups as controls in comparing this phcnomenon for significant difference in patients with allergic respiratory diseost&. By use of the same formula, chi square = 10.28 n= 1 (one degree of freedom) p =
394
THE TABLE
~mmiv~f, III.
RACE
OF
ALLERGY
(CONTROL
GROUP)
WHITE Positive Negative Chi square
Intense Sweaters Intense Sweaters z 0.72, n ~1, p =
Intense Sweaters Intense Sweaters = 0.77, n ~1, p = TABLE
15-19
V.
120-24
NEGRO
I
TOTAL
I
FEMALE 19 91
I
TOTAL 27 135
FOR SIGNIFICANCE
OF AGE
0.50 - 0.30.
TABLE
Positive Negative Chi square
I
IV.
SEX
(CONTROL
GROUP)
MALE 8 44 0.70
CONTROL
) 25-29
- 0.80. GROUP
AGE (YEARS) 130-34 ) 35-39 / 40-44
Allergic Group Positive intense 7 5 3 2 3 Sweaters Negative intense 2 9 1 4 4 Sweaters Co&-o1 Group Positive intense 3 4 1 3 8 Sweaters Negative intense 4 5 9 11 20 Sweaters Chi square = 16.89, n = 1, p = 0.10 - 0.05. *3 Negro patients were unable to state age and
145-49
150-54
/ 55-59
160-65
1 TOTAL
0
1
3
2
0
26
4
7
3
3
0
37
2
1
3
1
1
27
20
20
15
16
12
132”
were
omitted.
This high value of p indicates that race is rrot a factor in the production of intense palmar sweating. The same procedure was applied to study the effect of sex on intense palmar sweating in the control group (Table IV). chi square = 0.77 n=l p = 0.70-0.80. Likewise this demonstrates that sex is not a factor in intense palmar sweating. To study the effect of age on intense palmar sweating, the control group was divided into five-year periods and p determined as above. The age distribution in the allergic group is included in Table V. Chi square = np =
16.89 9 0.10-0.05.
Age (from 15 to 65 years) is not a factor in intense palmar sweating. In conclusion, these data show that race, sex, and age (15 to 65 years) are not factors in intense palmar sweating, and that there is a significant difference in the incidence of intense palmar sweating between patients with clinically manifest allergic respiratory disease and nonallergic patients. In the absence of other known factors which would account for this difference, we must conclude that it is associated with the clinically overt allergic state.
COHEN
:
AUTONOMIC
NERVOUS
:<95
SYSTEM
COMMENT
The clinical observation of increased palmar sweating in disturbances of the autonomic nervous system long has been recognized. DaCostalO described it in 1871 as part of the picture of neurocirculatory asthenia. A significant increase in the incidence of intense palmar sweating in anxiety has been demonstrated.8 That psychoneurotic factors per se are not the explanation for the increased incidence of intense palmar sweating in allergic patients is indicated by the difference in incidence in these two groups of patients. On the other hand, increase in water and sodium loss in the urine has been conclusively shown to occur during allergic upsets.3 KernI looks upon this phenomenon as a defense mecllanism on the part of the body to deplete itself of fluid and thus favorably influencr the edema of the shock organ. The records of this study were made at a time of the year when asthma is common. It is interesting to speculate that pcrhal)s this phenomenon is explained on a similar compensatory mechanism. Or does this represent an inherent manifestation of autonomic nervous systcm imbalance? Does the individual with clinical allergic respiratory disease inherit a pattern of autonomic nervous system response which is the dct,crminina factor in the pathogenesis of clinically manifest allergy? II’ so, this would (1s plain the discrepancy between the degree of immlmologic and clinical hypersensitivity which is so commonly observed. It would likewise explain the high incidence of immunologically significant skin tests found in normal individuals, many of whom never develop clinical manifestations of allergic disease. This has been estimated to be between 5 and 10 per cent of the population.12 a genetic factor in the pattern of autonomic nervous system function 1~s been reported by Jost and Sontag, who studied autonomic activity in monozygotic twins, siblings, and controls, Statistically significant differences in autonomic nervous function were found between related and unrelated individuals.*” Further studies on the autonomic nervous system of the “atopic” individual are indicated. SUMMARY
1. Patients with allergic respiratory disease manifest a statistically significant increase in the incidence of intense palmar sweating as determined by the Silverman technique over patients wit,h psychoneurosis (civilian) and syphilis. 2. Race, sex, and age (15 to 65 years) are without influence on interlse palmar sweating ; therefore, the difference in incidence l~tv;ern the ;rllrrgk and nonallergic groups is due to factors associated with the clinically manifast, allergic state and are not sampling errors. 3. The significance of this phenomenon is discussed from the standpoint of disturbed water balance and cholinergic stimulation. 4. It seems probable that clinically manifest allergic respiratory disease in man is dependent on an inherent behavior pattern of the autonomic ncrvo\ls system in addition to the immunologic factor of hypersensitivity. We statistical
dh to express our thanks to analysis of the data in these
Dr. B. G. Efron experimenl3.
of
New
Orleans
for
his
aill
in rll~~
396
THE
JOURNAL
OF
ALLERGY
REFERENCES
1. Cook, 2. 3. 4. 5. 6. 7. a. 9. 10. 11. 12. 13.
W. M., and Stoesser, A. J.: Influence of Induced Variations in Electrolyte and Water Exchanges With Pitressin in Bronchial Asthma. Proe. Soe. Exper. Biol. & Med. 38: 636, 1938. Cook, W. M., and Stoesser, A. J.: Electrolyte and Water Exchange in Bronchial Asthma. J. ALLERGY 11: 65, 1939. Sheldon, J., Howes, H., and Stuart, G.: Observations on Total Water and Sodium Exchanges in Asthmatic Patients. J. ALLERGY 11: 1, 1939. French, T. M., and Alexander, F,: Psychogenic Factors in Bronchial Asthma. Part I. Baltimore, 1944. Psychosomatic Medicine Monographs IV. Rubin, S., and Moses, L.: Electroencephalographic Studies in Asthma With Some Personality Correlations. Psychosom. Med. 6: 31, 1944. Kuntz, 8.: The Autonomic Nervous System in Relation to Allergy. Ann. Allergy 3: 91, 1945. Silverman, J. J., and Powell, V. E.: Studies on Palmar Sweating. III. Palmar Sweating in an Army General Hospital. Psychosom. Med. 6: 243, 1944. Silverman, J. J., and Powell, V. E.: Studies on Palmar Sweating. I. A Technique for the Study of Palmar Sweating. Am. J. M. SC. 208: 297, 1944. Efron, B. G., Boatner, C. H., Pabst, M. R., and Feibleman, J. K.: Biologic Analysis in Allergy, Internat. Correspond. Club Allergy, 1941. An Irritable Form of Heart; A Clinical Study of a Functional Cardiac DaCosta, J. M.: Disorder and Its Consequences, Am. J. M. Se. 61: 2, 1871. of Allergy. Kern, R. A.: The Role of Water Balance in the Clinical Manifestations Am. J. M. SC. 199: 728, 1940. Efron, B. G., Boatner, C. H., and Pabst, M. R.: Studies With Antigens: The Significance of Scratch Test Reactions to Purified House Dust Extracts. J. Invest. Dermat. 3: 401, 1940. The Genetic Factor in Autonomic Nervous System Function. Jost, H., and Sontag, L. W.: Psychosom. Med. 6: 308, 1944.
STANLEY
OF THE
COHEN,
M.D.,
AUTONOMIC NERVOUS INDIVIDUALS*
AND
HORACE
L. WOLF,
SYSTEM
B.S.,
M.D.,
IN
NEW
L’ATOPLC”‘
ORLEANS.
IJA.
T
HE importance of hypersensitivity in hay fever and bronchial asthma is well recognized. However, it is a common observation that the majority of attacks of bronchial asthma cannot be explained by recent or increased contact with An outstanding example of substances to which the patient is hypersensitive. this is the part meteorologic disturbances play in the production of attacks in patients who are hypersensitive to environmental allergens which they contacdt the year around. There is little doubt that mechanisms which do not involve an antigen-antibody reaction contribute mat,erially to the clinical production of the attack. Little is known concerning these mechanisms. Several studies have been made on the disturbance of water and electrolyte balance in this disease.l-” These studies clearly indicate that these factors influence the occurrence of allergic l)henomena. The importance of emotional factors in the precipitation 0 allergic reactions is likewise well recognized. French and Alexander4 point out! that the psychogenic factor of fear of separation or estrangement from some mother figure tends to precipitate asthmatic attacks. ,\ccording to those authors, ill such a situation the asthmatic attacks seem to ha,rc the significance of a suppressed cry. The finding of an increased incidence in the dominant alpha type of electroencephalogram in asthmatic patients by Rubin and Moses5 is additional evidence of the importance of the nervous system in this disease. It, is quite possible that many of these nonspeoific, yet important causes of allergic upsets are mediated through the autonomic nervous system. KunW quite aptly calls attention to t,he evidence for autonomic imbalance ill allc~*g!~ disease. Vasodilatation occurring in the mucous membranes as a result nt’ cholinergic stimulation permit,s increased permeabilit,y of the capillary bed with tissue edema and the substratum for increased secretory output of the mucous glands. To quote Knntz, “ Some of the most, characteristic manifestations of allergic disease, therefore, are calrsally ~la~e(l to Iwightened parasympathetic or’ cholinergic reactivity.” With those ideas in mind, we decided to compare palmsr sweating of allergic and nonallergic patients. Sweat glands are supplied bp fibers of the sympatheiic *From the sity of Louisiana, Touro Infirmary.
Department Allergy
of Preventive Medicine, School of Clinic, Hutchinson Memorial Clinic
391
Medicine, and the
The Tulane Division of
UnivcrAllergy.
392
THE
JOURNAL
OF
ALLERGY
nervous system, but functionally they are cholinergic. Palmar sweating bears no relationship to water loss from other parts of the skin or respiratory tract. However, it occurs wit.h relative independence of environmental temperature, is continuous during waking hours and is influenced by emotional stimuli.’ PROCEDURE
Three groups of patients were studied. No individuals below 15 years or above 65 years of age were included. Members of both sexes and the white and Negro races were examined without selection. The first group consisted of 63 patients with allergic respiratory disease. The diagnosis in each case was made clinically and substantiated by secretion or blood eosinophilia in some cases, and positive skin tests in all cases. About three-fourths of those patients had sustained clear-cut attacks of bronchial asthma. Where anxiety was apparent, as manifested by palpitation, tremor, tenseness, weakness, dilated pupils, sleep disturbances, or psychological phenomena of a defensive nature, such as conversion symptoms or phobias existed, the patient was excluded from this group. This was an uncommon occurrence. The second group consisted of 63 psychoneurotic patients from the neuropsychiatric service of Touro Infirmary. These patients were studied as they returned for routine visits. None with overt organic nervous system disease, psychoses, syphilis, or allergic disease were included. This group was studied in order to assess the psychiatric factor in palmar sweating in the clinic group of patients. The third group of 99 syphilitic patients was selected because they presented an analagous situation in the clinic to the allergic group. These patients were all awaiting injections of mapharsen or bismuth. Thus, they afforded a comparison to the allergic patients, the majority of whom also were anticipating parenteral medication. Patients with overt nervous system, circulatory, or allergic disea,se were excluded from this group. The method used to measure palmar sweating was that of Silverman and PowelLs Briefly, it consists of the application of an alcoholic solution of ferric chloride to the palm. The alcohol is allowed to evaporate. The palm is exposed for a standard time to a paper impregnated with tannic acid. The intensity of the ink produced on the paper is proporti0nat.e to the amount of sweat liberated from the palm. All patients were studied during their routine visits to the clinic, No patient was studied during or immediately following a spell of asthma or a dose of epinephrine or ephedrine. However, all were studied at a time of the year (spring) TABLE DEGREE
OF
RESPONSE
-T 1:: IV Total Percentage
III
and
IV
I
ALLERGIC
I I-
PSYCHONEUROTIC
1
SYPHILITIC
28
31
50
149 12
195
n59
5 63
5 99
20
14
63 41
COHEN
:
AUTONOMIC
when allergic upsets are common cording to the method advocated intense reactions (Table I). All purposes of comparison, Groups compared to Groups III and IV TABLE
II.
COMPARISON
NERVOUS
393
STSTl$XI
in New Orleans, The papers were graded, acby Silverman, into four gl’onps: from mild to records were read at the same sitting. For I and II (negative intense sweaters) w(tt’(’ (positive intense sweaters) (Table II).
0% THE
OBSERVATIONS
&PHII,ITIC
AND
AND
PSY~IIO~~EUR~TIC
GIWW
ANALYSIS
The incidence of intense palmar sweating was found to be 41 per cent, in the allergic group, 20 per cent in the psychoneurotic group, and 14 PCV cent in the syphilitic group. The chi square statistic (Brandt-Snedecor formula” ) was ~~scti to c:ll(A~~ht~: probability, and the psychoneurotic and syphilitic groups of patient,s were cornpared for significant differences. By this method. chi square = 1.17 n-l (one degree of freedom) p = 0.20-0.30 This high value of p indicates that there is no significant difference in the incidence of intense palmar sweating in patients with syphilitic and psychoneurotic disease, both being nonallergic. We may, therefore, use both groups as controls in comparing this phcnomenon for significant difference in patients with allergic respiratory diseost&. By use of the same formula, chi square = 10.28 n= 1 (one degree of freedom) p =
394
THE TABLE
~mmiv~f, III.
RACE
OF
ALLERGY
(CONTROL
GROUP)
WHITE Positive Negative Chi square
Intense Sweaters Intense Sweaters z 0.72, n ~1, p =
Intense Sweaters Intense Sweaters = 0.77, n ~1, p = TABLE
15-19
V.
120-24
NEGRO
I
TOTAL
I
FEMALE 19 91
I
TOTAL 27 135
FOR SIGNIFICANCE
OF AGE
0.50 - 0.30.
TABLE
Positive Negative Chi square
I
IV.
SEX
(CONTROL
GROUP)
MALE 8 44 0.70
CONTROL
) 25-29
- 0.80. GROUP
AGE (YEARS) 130-34 ) 35-39 / 40-44
Allergic Group Positive intense 7 5 3 2 3 Sweaters Negative intense 2 9 1 4 4 Sweaters Co&-o1 Group Positive intense 3 4 1 3 8 Sweaters Negative intense 4 5 9 11 20 Sweaters Chi square = 16.89, n = 1, p = 0.10 - 0.05. *3 Negro patients were unable to state age and
145-49
150-54
/ 55-59
160-65
1 TOTAL
0
1
3
2
0
26
4
7
3
3
0
37
2
1
3
1
1
27
20
20
15
16
12
132”
were
omitted.
This high value of p indicates that race is rrot a factor in the production of intense palmar sweating. The same procedure was applied to study the effect of sex on intense palmar sweating in the control group (Table IV). chi square = 0.77 n=l p = 0.70-0.80. Likewise this demonstrates that sex is not a factor in intense palmar sweating. To study the effect of age on intense palmar sweating, the control group was divided into five-year periods and p determined as above. The age distribution in the allergic group is included in Table V. Chi square = np =
16.89 9 0.10-0.05.
Age (from 15 to 65 years) is not a factor in intense palmar sweating. In conclusion, these data show that race, sex, and age (15 to 65 years) are not factors in intense palmar sweating, and that there is a significant difference in the incidence of intense palmar sweating between patients with clinically manifest allergic respiratory disease and nonallergic patients. In the absence of other known factors which would account for this difference, we must conclude that it is associated with the clinically overt allergic state.
COHEN
:
AUTONOMIC
NERVOUS
:<95
SYSTEM
COMMENT
The clinical observation of increased palmar sweating in disturbances of the autonomic nervous system long has been recognized. DaCostalO described it in 1871 as part of the picture of neurocirculatory asthenia. A significant increase in the incidence of intense palmar sweating in anxiety has been demonstrated.8 That psychoneurotic factors per se are not the explanation for the increased incidence of intense palmar sweating in allergic patients is indicated by the difference in incidence in these two groups of patients. On the other hand, increase in water and sodium loss in the urine has been conclusively shown to occur during allergic upsets.3 KernI looks upon this phenomenon as a defense mecllanism on the part of the body to deplete itself of fluid and thus favorably influencr the edema of the shock organ. The records of this study were made at a time of the year when asthma is common. It is interesting to speculate that pcrhal)s this phenomenon is explained on a similar compensatory mechanism. Or does this represent an inherent manifestation of autonomic nervous systcm imbalance? Does the individual with clinical allergic respiratory disease inherit a pattern of autonomic nervous system response which is the dct,crminina factor in the pathogenesis of clinically manifest allergy? II’ so, this would (1s plain the discrepancy between the degree of immlmologic and clinical hypersensitivity which is so commonly observed. It would likewise explain the high incidence of immunologically significant skin tests found in normal individuals, many of whom never develop clinical manifestations of allergic disease. This has been estimated to be between 5 and 10 per cent of the population.12 a genetic factor in the pattern of autonomic nervous system function 1~s been reported by Jost and Sontag, who studied autonomic activity in monozygotic twins, siblings, and controls, Statistically significant differences in autonomic nervous function were found between related and unrelated individuals.*” Further studies on the autonomic nervous system of the “atopic” individual are indicated. SUMMARY
1. Patients with allergic respiratory disease manifest a statistically significant increase in the incidence of intense palmar sweating as determined by the Silverman technique over patients wit,h psychoneurosis (civilian) and syphilis. 2. Race, sex, and age (15 to 65 years) are without influence on interlse palmar sweating ; therefore, the difference in incidence l~tv;ern the ;rllrrgk and nonallergic groups is due to factors associated with the clinically manifast, allergic state and are not sampling errors. 3. The significance of this phenomenon is discussed from the standpoint of disturbed water balance and cholinergic stimulation. 4. It seems probable that clinically manifest allergic respiratory disease in man is dependent on an inherent behavior pattern of the autonomic ncrvo\ls system in addition to the immunologic factor of hypersensitivity. We statistical
dh to express our thanks to analysis of the data in these
Dr. B. G. Efron experimenl3.
of
New
Orleans
for
his
aill
in rll~~
396
THE
JOURNAL
OF
ALLERGY
REFERENCES
1. Cook, 2. 3. 4. 5. 6. 7. a. 9. 10. 11. 12. 13.
W. M., and Stoesser, A. J.: Influence of Induced Variations in Electrolyte and Water Exchanges With Pitressin in Bronchial Asthma. Proe. Soe. Exper. Biol. & Med. 38: 636, 1938. Cook, W. M., and Stoesser, A. J.: Electrolyte and Water Exchange in Bronchial Asthma. J. ALLERGY 11: 65, 1939. Sheldon, J., Howes, H., and Stuart, G.: Observations on Total Water and Sodium Exchanges in Asthmatic Patients. J. ALLERGY 11: 1, 1939. French, T. M., and Alexander, F,: Psychogenic Factors in Bronchial Asthma. Part I. Baltimore, 1944. Psychosomatic Medicine Monographs IV. Rubin, S., and Moses, L.: Electroencephalographic Studies in Asthma With Some Personality Correlations. Psychosom. Med. 6: 31, 1944. Kuntz, 8.: The Autonomic Nervous System in Relation to Allergy. Ann. Allergy 3: 91, 1945. Silverman, J. J., and Powell, V. E.: Studies on Palmar Sweating. III. Palmar Sweating in an Army General Hospital. Psychosom. Med. 6: 243, 1944. Silverman, J. J., and Powell, V. E.: Studies on Palmar Sweating. I. A Technique for the Study of Palmar Sweating. Am. J. M. SC. 208: 297, 1944. Efron, B. G., Boatner, C. H., Pabst, M. R., and Feibleman, J. K.: Biologic Analysis in Allergy, Internat. Correspond. Club Allergy, 1941. An Irritable Form of Heart; A Clinical Study of a Functional Cardiac DaCosta, J. M.: Disorder and Its Consequences, Am. J. M. Se. 61: 2, 1871. of Allergy. Kern, R. A.: The Role of Water Balance in the Clinical Manifestations Am. J. M. SC. 199: 728, 1940. Efron, B. G., Boatner, C. H., and Pabst, M. R.: Studies With Antigens: The Significance of Scratch Test Reactions to Purified House Dust Extracts. J. Invest. Dermat. 3: 401, 1940. The Genetic Factor in Autonomic Nervous System Function. Jost, H., and Sontag, L. W.: Psychosom. Med. 6: 308, 1944.