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Prognosis in arterial hypertension
Prognosis Comparison
in Arterial
Hypertension*
between 251 Patients after Sympathectomy and a Selected Series of 435 Non -oberated Patients 1
SVEN
HAMMARSTR~M,
Stockholm,
M.D.
and POUL
Sweden
BECHGAARD,
M.D.
Aarhus, Denmark
T
HE beneficial effects of neurosurgical treatment of hypertension have been fully proved by several reports on its effects on blood pressure, hypertensive retinopathy, cardiac function and subjective symptoms. e-16 But in spite of the large clinical experience with neurosurgical treatment information as to its effect on life expectancy is limited due to the difficulty “to find comparable data in the literature concerning the prognosis for hypertensive patients treated medically or untreated.“15 Peet and Isberg have shown that dorsal ganglionand splanchnicectomy changed the survival rate after more than five years in malignant hypertension from less than 1 to more than 20 per cent. They used the Keith, Wagener and Barker* figures as controls. Smithwick15 compared the survival rate in the same controls with his own series of 256 hypertensives followed five to nine years after lumbodorsal sympathectomy. The prognosis was better in all groups of the surgically treated patients. The difference observed was statistically significant for groups II, III and IV. In groups II? and IV the survival rates in the operated series comprising seventy and thirty-nine patients, respectively, was 70 and 75 per cent as compared with 9 and less than 1 per cent in the non-operated series of 37 and 146 patients, respectively. Groups I and II of Keith, Wagener and Barker include ten and twenty-six patients, figures too limited for conclusions regarding the life expectancy in these groups.
One of us (Bechgaard) l has followed-up a series of 1,000 non-operated hypertensive patients. Neither this nor any other unselected series is suitable for comparison with operated groups which are selected according to certain rules. This is demonstrated by the fact that retinal exudates occurred in only 1 per cent of Bechgaard’s series and in 31 per cent of the present series of operated patients. In Bechgaard’s series the mortality rate in men was twice as high as in women. In patients with signs of myocardial damage by ECG the mortality figure was 547 as compared with 207 in hypertensives without such changes and 100 in the average population of the same age groups. The present series of 251 operated patients has been followed two to eight years after sympathectomy. It includes all hypertensives operated on at the Neurosurgical Clinic of the Serafimer Hospital in Stockholm from February, 1940 to August 1946, with the exception of three patients who have not been traced. Five patients in the whole series died in consequence of the operation. Since 1943 there has been no operative mortality in a consecutive series of 250 hypertensives. One hundred forty-eight patients have been submitted to bilateral lumbodorsal ganglionand splanchnicectomy from Thg or Thlo to L1 according to Smithwick; of these twenty-four later died. Sixty-four patients were operated on bilaterally according to Peet; of these thirteen died. Thirty-one were operated on only
* From the Neurosurgical Clinic of the Serafimer Hospital and the Ivth Medical Service of St. Erik’s Hospital, Stockholm, Sweden, and from the Municipal Hospital n Division, Copenhagen, and Amtssygehuset, Medical Service. Aarhus, Denmark. JANUARY,
1950
53
Prognosis in Hypertension
54
one side and eighteen of them are dead. Most of the patients with unilateral sympathectomy were’ in a poor state before the operation. For a description of the criteria used by us in the selec’tion of patients for sympathectomy the reader is referred to TABLE DISTRIBUTION
OF
OPERATED
IN
AGE AND
251
-Hurnmarstriim,
Bechgaard
with uncomplicated hypertensive disease tyithout marked subjective symptoms. Patients with such benign hypertension are not selected for sympathectomy. The life expectancy of this group has been indicated by Bechgaard.l Group II includes those with TABLE
I
VARIOUS
GROUPS
SURGICALLY
OF
435
NON-
DISTRIBUTION IN
TREATED
435
OF
IN 251
II
PRESSURE
NON-OPERATED
OPERATION
HYPERTENSIVES
BLOOD
AT
FIRST EXAMINATION AND
HYPERTENSIVES SURGICALLY
TREATED
Group
Group
IV
III
BEFORE
PATIENTS
Group
Operated
77
No. of Cases
94
_.
.._..
9 16 54 21 ,.. ~______ 100
1 15 41 35 3 100
4 18 50 27 1 100
“; 38 47 10 100
177
NO1 Oper_ ated
86
164
Per Cent
Per Cent Aw o-29.. .._......, 30-39 40-49. 50-59.. GO-65........
88
II
9 27 47 17 ____ 100
2 16 35 40 7
Systolic Pressure
7 16 23 31 23
2 15 22 25 36
8 26 30 21 15
10 23 26 28 13
23 34 21 12 10
100
100
100
100
100
100
-----
100
HammarstrGm* and a more detailed investigation which is to be published by us this year. The non-operated series was selected according to the same rules as the patients operated on and followed-up two to ten years. In this series 95 per cent, 435 patients, were traced. They have been collected (some of them by Dr. Soegaard)r’ from about 130,000 records from various hospitals in Copenhagen and the St. Erik’s Hospital in Stockholm. The age distribution is seen in Table I. The distribution of blood pressure at the first examination is seen in Table II. The average age of the patients was slightly lower in the operated than in the nonoperated group (43.0 and 49.6 years). In all groups of the operated series a greater percentage showed higher systolic and diastolic levels than the non-operated. We have divided our material into four groups; men and women are treated separately. The first group of patients was not included in this study as it contained those
5 17 25 53
. .
Per Cent
Diastolic Pressure
.
. 1 12 55 32
,..
100
marked subjective symptoms but without signs of myocardial damage. They may show left axis deviation in the ECG and/or a relative enlargement of the left ventricle if the heart volume is within normal limits according to teleradiography. The retinal changes in the patients in our second group are classified as group I or II according to Keith and Wagener. Group III includes those with the same eyeground changes or, in addition, retinal hemorrhages with or without signs of thrombosis of the retinal vessels. Patients in group III further show one or more of the following signs of cardiovascular damage: negative Ti in the ECG, heart volume above the predicted normal (500 ml./M.* body surface in men and AMERICAN
JOURNAL
OF
MEDICINE
Prognosis
in Hypertension---
liammarstrkn,
450 ~lll./M.~ in women, or the transverse diameter of the heart greater than onehalf the inner thoracic diameter), residual damage after cerebral insult and constant albuminuria. In group IV we include all hypertensives with definite retinal exudates and/or papillary protrusion since we found the life expectancy to be about the same if the patients in this group did or did not have papillary protrusion. Patients with cardiac decompensation at rest, auricular fibrillation, myocardial infarct or renal insufficiency were not included in the non-operated series. A few patients in the operated series had cardiac insufficiency and were compensated with digitalis before operation while another minor group showed renal insufficiency before operation. All of them died, mostly within a year after operation. In the patients with primary malignant hypertension in the control series the time of observation was counted from the date of their first symptoms even if the retinal exudates were first observed later. In the operated series the time of observation was always counted from the operation. This
OF SURVIVAL
IN
-
VARIOUS
GROUPS
-
TABLE COMPARISON TENSNES
Years of Observation
Men
ated
-
1
-
1
1”
_
ated
.
Mortality rate (per milk). Operated no. of casea. DC&8. Mortality rate (per milk). Error of mean of differences (per mine)... Significance of differences of means in unoperated and operated patients (per cent).
.
\Nomen
MelI
1
i _._~~ MelI
__
__
Vomen
--
69 68
25 24
83 57
94
44
42 9
122 21
307
330
181
80
41
20
38 18
41 16
35 9
50 8
29 4
58 0
150
96
52
33
25
80
115
56
37
42
.
93.5
59.3
98
98
-
- -
-
45
30
-
-
-
IV AND
NON-OPERATED
-
HYPERTENSIVES*
Group
Women
II
ated
Men
Women
__
T ,Oper-
ated
III
No.
Deaths.
Men
Not Oper-
HYPER-
_-
.-
T ,Oper-
Operated
-
-
OF OPERATED
Women
Not
UNOPERATED
251 HYPERTENSNES AFTER SYMPATHECTOMY
1Men
Unoperated ofcases..
III
453
IN
Group III
--
,Oper-
AND
PROGNOSIS
.-
-
_
OF
GKNJp
Group IV
-
5.5
method of calculation gave a higher signihcance to the difference between the operated and non-operated patients than is shown by the figures. The period of observation has been divided into one-year intervals. The mortality rate is calculated by dividing the
TABLE RATE
Bechgaard
Not Operated
Operated
Not Oper-
,Operated
ated
Not
Not Oper-
,Oper-
Operated
ated
ated
__ 0 1 2 3 4 5 6 7 8 9 10
100 76 61 55 53 48 46 35 32 27 24
-
-
100 90 78 75 64 51 39 32 20 15 10
100 67 42 22 15 15 6 4 3 3 1
-
* The figures indicate the percentage
lated. JANUARY,
1950
100 72 56 36 16 12 4 4 4 0 0
100 95 86 84 81 78 72 67 64 58 56
-
100 83 67 55 44 38 30 25 19 16 13
100 90 88 85 85 82 82 80 78 76 72
100 96 86 80 76 70 65 56 51 48 45
100
-
100 93 87 85 80 78 75 73 70 65 60
100 98 98 94 93 90 85 84 83 80 78
-
-
of survivals. Prognosis in operated patients in group n cannot yet be calcu-
56
Prognosis
in Hypertension-
number of dead during each year by the number of persons in the group at the beginning of the year which indicates the probability of death within one year expressed per thousand. l The results of comparison between the patients are operated and the control shown in Table III. The prognosis is consistently better in the operated than in the non-operated patients. In patients with retinal exudates (group IV) this difference is statistically significant in both sexes. In this as in other series of hypertensives the frequency of malignant hypertension is higher in men than in women (36 against 17 per cent). In the unoperated series in group IV the prognosis is about equally poor in men as in women. In groups II and III the mortality rate is more than twice as high in men as in women. In men with signs of cardiovascular damage (group III) the prognosis is significantly better in the operated than in the control series. The significance of the lower mortality rate in the operated women in group III compared with the controls in this group is less pronounced, but it is still 60 per cent. In group II the life expectancy is favorable and we need a longer follow-up time to decide if the neurosurgical treatment significantly improved the prognosis. With a longer period of observation, the difference may be conclusive since we already have nearly twice as high a mortality rate in the male controls as in the operated series and no mortality among fifty-eight operated women against twenty deaths in 122 controls. In Table IV we have calculated the probable duration of life in the various groups of controls and operated patients. The figures indicate the percentage of survivals after various years of observation.
-Hammarstr6m,
Bechgaard SUMMARY
Our data demonstrate the beneficial effect of sympathectomy on life expectancy in patients suffering from essential hypertension. A new classification of essential hypertension, based on the clinical findings which have proved to be of greatest prognostic value, is proposed. REFERENCES 1. BECHGAARD, P. Arterial hypertension. Acta med. Scandinav. SuppI., 172, 1946. 2.’ HAMMARSTR~M,S. Arterial hypertension. Acta med. Scandinav. Suppl., 192, 1947. 3. PEET, M. M. and ISBERG, E. M. The problem of malignant hypertension and its treatment by snlanchnic resection. Ann. Int. Med.. 28: 755. 1948. 4. KEITH, N. M., WACENER, H. P. and BARKER,‘N. W. Some different types of essential hypertension: their course and prognosis. Am. J. M. SC., 197: 332, 1939. 5. BRIDGES, W. C., JOHNSON,A. L., SMITHWICK,R. H. and WHITE, P. D. Electrocardiography in hypertension. Study of patients subjected to lumbodorsal splanchnicectomy. 3. A. M. A., 131: 1476, 1946. 6. CANABAL, E. J., WARNEFORD-THOMSON, H. F. and WHITE, P. D. The electrocardiogram in hypertension. III. Am. HeartJ., 30: 189, 1945. 7. FISHBERG, A. M. Sympathectomy for essential hypertension. .7. A. M. A., 137: 670, 1948. 8. GRIMSON,K. S. The surgical treatment of hypertension. Adv. Znt. Med., 2: 173, 1947. 9. HINTON,J. W. and LORD, J. W., JR. Thoracolumbar sympathectomy in the treatment of advanced essential hypertension. New 3TorkState 3. Med., 46: 1223, 1946. 10. COHEN, M. Ophthalmoscopic changes associated with hypertensive vascular disease as a guide to sympathectomy. Arch. Ophth., 37: 491, 1947. 11. PEET, M. M. Hypertension and its surgical treatment by supradiaphragmatic splanchnicectomy. Am. 3. Surg., 75: 48, 1948. 12. PEET, M. M. and ISBERG, E. M. The surgical treatment of arterial hypertension. 3. A. M. A., 130: 467,1946. 13. POPPEN, J. L. and LEMON, C. Surgical treatment of hypertension. 3. A. M. A., 134: 1, 1947. 14. SMITHWICK, R. H. Surgical treatment of hypertension. Am. 3. Med., 4: 744, 1948. 15. SMITHWICK, R. H. Continued hypertension. &it. M. J,, July, 1948. 16. PALMER, R. S. Surgical treatment of hypertension. 3. A. M. A., 134: 9, 1947. 17. SOEBYE, P. Heredity in Essential Hypertension. Copenhagen, 1948.
AMERICAN
JOURNAL
OF
MEDICINE
in Arterial
Hypertension*
between 251 Patients after Sympathectomy and a Selected Series of 435 Non -oberated Patients 1
SVEN
HAMMARSTR~M,
Stockholm,
M.D.
and POUL
Sweden
BECHGAARD,
M.D.
Aarhus, Denmark
T
HE beneficial effects of neurosurgical treatment of hypertension have been fully proved by several reports on its effects on blood pressure, hypertensive retinopathy, cardiac function and subjective symptoms. e-16 But in spite of the large clinical experience with neurosurgical treatment information as to its effect on life expectancy is limited due to the difficulty “to find comparable data in the literature concerning the prognosis for hypertensive patients treated medically or untreated.“15 Peet and Isberg have shown that dorsal ganglionand splanchnicectomy changed the survival rate after more than five years in malignant hypertension from less than 1 to more than 20 per cent. They used the Keith, Wagener and Barker* figures as controls. Smithwick15 compared the survival rate in the same controls with his own series of 256 hypertensives followed five to nine years after lumbodorsal sympathectomy. The prognosis was better in all groups of the surgically treated patients. The difference observed was statistically significant for groups II, III and IV. In groups II? and IV the survival rates in the operated series comprising seventy and thirty-nine patients, respectively, was 70 and 75 per cent as compared with 9 and less than 1 per cent in the non-operated series of 37 and 146 patients, respectively. Groups I and II of Keith, Wagener and Barker include ten and twenty-six patients, figures too limited for conclusions regarding the life expectancy in these groups.
One of us (Bechgaard) l has followed-up a series of 1,000 non-operated hypertensive patients. Neither this nor any other unselected series is suitable for comparison with operated groups which are selected according to certain rules. This is demonstrated by the fact that retinal exudates occurred in only 1 per cent of Bechgaard’s series and in 31 per cent of the present series of operated patients. In Bechgaard’s series the mortality rate in men was twice as high as in women. In patients with signs of myocardial damage by ECG the mortality figure was 547 as compared with 207 in hypertensives without such changes and 100 in the average population of the same age groups. The present series of 251 operated patients has been followed two to eight years after sympathectomy. It includes all hypertensives operated on at the Neurosurgical Clinic of the Serafimer Hospital in Stockholm from February, 1940 to August 1946, with the exception of three patients who have not been traced. Five patients in the whole series died in consequence of the operation. Since 1943 there has been no operative mortality in a consecutive series of 250 hypertensives. One hundred forty-eight patients have been submitted to bilateral lumbodorsal ganglionand splanchnicectomy from Thg or Thlo to L1 according to Smithwick; of these twenty-four later died. Sixty-four patients were operated on bilaterally according to Peet; of these thirteen died. Thirty-one were operated on only
* From the Neurosurgical Clinic of the Serafimer Hospital and the Ivth Medical Service of St. Erik’s Hospital, Stockholm, Sweden, and from the Municipal Hospital n Division, Copenhagen, and Amtssygehuset, Medical Service. Aarhus, Denmark. JANUARY,
1950
53
Prognosis in Hypertension
54
one side and eighteen of them are dead. Most of the patients with unilateral sympathectomy were’ in a poor state before the operation. For a description of the criteria used by us in the selec’tion of patients for sympathectomy the reader is referred to TABLE DISTRIBUTION
OF
OPERATED
IN
AGE AND
251
-Hurnmarstriim,
Bechgaard
with uncomplicated hypertensive disease tyithout marked subjective symptoms. Patients with such benign hypertension are not selected for sympathectomy. The life expectancy of this group has been indicated by Bechgaard.l Group II includes those with TABLE
I
VARIOUS
GROUPS
SURGICALLY
OF
435
NON-
DISTRIBUTION IN
TREATED
435
OF
IN 251
II
PRESSURE
NON-OPERATED
OPERATION
HYPERTENSIVES
BLOOD
AT
FIRST EXAMINATION AND
HYPERTENSIVES SURGICALLY
TREATED
Group
Group
IV
III
BEFORE
PATIENTS
Group
Operated
77
No. of Cases
94
_.
.._..
9 16 54 21 ,.. ~______ 100
1 15 41 35 3 100
4 18 50 27 1 100
“; 38 47 10 100
177
NO1 Oper_ ated
86
164
Per Cent
Per Cent Aw o-29.. .._......, 30-39 40-49. 50-59.. GO-65........
88
II
9 27 47 17 ____ 100
2 16 35 40 7
Systolic Pressure
7 16 23 31 23
2 15 22 25 36
8 26 30 21 15
10 23 26 28 13
23 34 21 12 10
100
100
100
100
100
100
-----
100
HammarstrGm* and a more detailed investigation which is to be published by us this year. The non-operated series was selected according to the same rules as the patients operated on and followed-up two to ten years. In this series 95 per cent, 435 patients, were traced. They have been collected (some of them by Dr. Soegaard)r’ from about 130,000 records from various hospitals in Copenhagen and the St. Erik’s Hospital in Stockholm. The age distribution is seen in Table I. The distribution of blood pressure at the first examination is seen in Table II. The average age of the patients was slightly lower in the operated than in the nonoperated group (43.0 and 49.6 years). In all groups of the operated series a greater percentage showed higher systolic and diastolic levels than the non-operated. We have divided our material into four groups; men and women are treated separately. The first group of patients was not included in this study as it contained those
5 17 25 53
. .
Per Cent
Diastolic Pressure
.
. 1 12 55 32
,..
100
marked subjective symptoms but without signs of myocardial damage. They may show left axis deviation in the ECG and/or a relative enlargement of the left ventricle if the heart volume is within normal limits according to teleradiography. The retinal changes in the patients in our second group are classified as group I or II according to Keith and Wagener. Group III includes those with the same eyeground changes or, in addition, retinal hemorrhages with or without signs of thrombosis of the retinal vessels. Patients in group III further show one or more of the following signs of cardiovascular damage: negative Ti in the ECG, heart volume above the predicted normal (500 ml./M.* body surface in men and AMERICAN
JOURNAL
OF
MEDICINE
Prognosis
in Hypertension---
liammarstrkn,
450 ~lll./M.~ in women, or the transverse diameter of the heart greater than onehalf the inner thoracic diameter), residual damage after cerebral insult and constant albuminuria. In group IV we include all hypertensives with definite retinal exudates and/or papillary protrusion since we found the life expectancy to be about the same if the patients in this group did or did not have papillary protrusion. Patients with cardiac decompensation at rest, auricular fibrillation, myocardial infarct or renal insufficiency were not included in the non-operated series. A few patients in the operated series had cardiac insufficiency and were compensated with digitalis before operation while another minor group showed renal insufficiency before operation. All of them died, mostly within a year after operation. In the patients with primary malignant hypertension in the control series the time of observation was counted from the date of their first symptoms even if the retinal exudates were first observed later. In the operated series the time of observation was always counted from the operation. This
OF SURVIVAL
IN
-
VARIOUS
GROUPS
-
TABLE COMPARISON TENSNES
Years of Observation
Men
ated
-
1
-
1
1”
_
ated
.
Mortality rate (per milk). Operated no. of casea. DC&8. Mortality rate (per milk). Error of mean of differences (per mine)... Significance of differences of means in unoperated and operated patients (per cent).
.
\Nomen
MelI
1
i _._~~ MelI
__
__
Vomen
--
69 68
25 24
83 57
94
44
42 9
122 21
307
330
181
80
41
20
38 18
41 16
35 9
50 8
29 4
58 0
150
96
52
33
25
80
115
56
37
42
.
93.5
59.3
98
98
-
- -
-
45
30
-
-
-
IV AND
NON-OPERATED
-
HYPERTENSIVES*
Group
Women
II
ated
Men
Women
__
T ,Oper-
ated
III
No.
Deaths.
Men
Not Oper-
HYPER-
_-
.-
T ,Oper-
Operated
-
-
OF OPERATED
Women
Not
UNOPERATED
251 HYPERTENSNES AFTER SYMPATHECTOMY
1Men
Unoperated ofcases..
III
453
IN
Group III
--
,Oper-
AND
PROGNOSIS
.-
-
_
OF
GKNJp
Group IV
-
5.5
method of calculation gave a higher signihcance to the difference between the operated and non-operated patients than is shown by the figures. The period of observation has been divided into one-year intervals. The mortality rate is calculated by dividing the
TABLE RATE
Bechgaard
Not Operated
Operated
Not Oper-
,Operated
ated
Not
Not Oper-
,Oper-
Operated
ated
ated
__ 0 1 2 3 4 5 6 7 8 9 10
100 76 61 55 53 48 46 35 32 27 24
-
-
100 90 78 75 64 51 39 32 20 15 10
100 67 42 22 15 15 6 4 3 3 1
-
* The figures indicate the percentage
lated. JANUARY,
1950
100 72 56 36 16 12 4 4 4 0 0
100 95 86 84 81 78 72 67 64 58 56
-
100 83 67 55 44 38 30 25 19 16 13
100 90 88 85 85 82 82 80 78 76 72
100 96 86 80 76 70 65 56 51 48 45
100
-
100 93 87 85 80 78 75 73 70 65 60
100 98 98 94 93 90 85 84 83 80 78
-
-
of survivals. Prognosis in operated patients in group n cannot yet be calcu-
56
Prognosis
in Hypertension-
number of dead during each year by the number of persons in the group at the beginning of the year which indicates the probability of death within one year expressed per thousand. l The results of comparison between the patients are operated and the control shown in Table III. The prognosis is consistently better in the operated than in the non-operated patients. In patients with retinal exudates (group IV) this difference is statistically significant in both sexes. In this as in other series of hypertensives the frequency of malignant hypertension is higher in men than in women (36 against 17 per cent). In the unoperated series in group IV the prognosis is about equally poor in men as in women. In groups II and III the mortality rate is more than twice as high in men as in women. In men with signs of cardiovascular damage (group III) the prognosis is significantly better in the operated than in the control series. The significance of the lower mortality rate in the operated women in group III compared with the controls in this group is less pronounced, but it is still 60 per cent. In group II the life expectancy is favorable and we need a longer follow-up time to decide if the neurosurgical treatment significantly improved the prognosis. With a longer period of observation, the difference may be conclusive since we already have nearly twice as high a mortality rate in the male controls as in the operated series and no mortality among fifty-eight operated women against twenty deaths in 122 controls. In Table IV we have calculated the probable duration of life in the various groups of controls and operated patients. The figures indicate the percentage of survivals after various years of observation.
-Hammarstr6m,
Bechgaard SUMMARY
Our data demonstrate the beneficial effect of sympathectomy on life expectancy in patients suffering from essential hypertension. A new classification of essential hypertension, based on the clinical findings which have proved to be of greatest prognostic value, is proposed. REFERENCES 1. BECHGAARD, P. Arterial hypertension. Acta med. Scandinav. SuppI., 172, 1946. 2.’ HAMMARSTR~M,S. Arterial hypertension. Acta med. Scandinav. Suppl., 192, 1947. 3. PEET, M. M. and ISBERG, E. M. The problem of malignant hypertension and its treatment by snlanchnic resection. Ann. Int. Med.. 28: 755. 1948. 4. KEITH, N. M., WACENER, H. P. and BARKER,‘N. W. Some different types of essential hypertension: their course and prognosis. Am. J. M. SC., 197: 332, 1939. 5. BRIDGES, W. C., JOHNSON,A. L., SMITHWICK,R. H. and WHITE, P. D. Electrocardiography in hypertension. Study of patients subjected to lumbodorsal splanchnicectomy. 3. A. M. A., 131: 1476, 1946. 6. CANABAL, E. J., WARNEFORD-THOMSON, H. F. and WHITE, P. D. The electrocardiogram in hypertension. III. Am. HeartJ., 30: 189, 1945. 7. FISHBERG, A. M. Sympathectomy for essential hypertension. .7. A. M. A., 137: 670, 1948. 8. GRIMSON,K. S. The surgical treatment of hypertension. Adv. Znt. Med., 2: 173, 1947. 9. HINTON,J. W. and LORD, J. W., JR. Thoracolumbar sympathectomy in the treatment of advanced essential hypertension. New 3TorkState 3. Med., 46: 1223, 1946. 10. COHEN, M. Ophthalmoscopic changes associated with hypertensive vascular disease as a guide to sympathectomy. Arch. Ophth., 37: 491, 1947. 11. PEET, M. M. Hypertension and its surgical treatment by supradiaphragmatic splanchnicectomy. Am. 3. Surg., 75: 48, 1948. 12. PEET, M. M. and ISBERG, E. M. The surgical treatment of arterial hypertension. 3. A. M. A., 130: 467,1946. 13. POPPEN, J. L. and LEMON, C. Surgical treatment of hypertension. 3. A. M. A., 134: 1, 1947. 14. SMITHWICK, R. H. Surgical treatment of hypertension. Am. 3. Med., 4: 744, 1948. 15. SMITHWICK, R. H. Continued hypertension. &it. M. J,, July, 1948. 16. PALMER, R. S. Surgical treatment of hypertension. 3. A. M. A., 134: 9, 1947. 17. SOEBYE, P. Heredity in Essential Hypertension. Copenhagen, 1948.
AMERICAN
JOURNAL
OF
MEDICINE