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heir origin in overdosage with thyroid extract in too vigorous an attempt to cure a colloid goiter。 One of the most striking characteristics of Graves' disease is the patient's loss of control and his increased susceptibility to stimuli； especially to trauma and to fear and to the administration of thyroid extract。 It has been shown that the various causes of the discharge of nervous energy produce alterations in the nervous system and probably in the thyroid gland。 This is especially true of the fear stimulus； and has been clearly demonstrated in the brains of rabbits which had been subjected to fear alone （Fig。 13）。 Of special interest was the effect of daily fright。 In this case the brain…cells showed a distinct change； although the animal had been subjected to no fear for twenty…four hours before it was killed （Fig。 13 C。 Now； a great distinction between man and the lower animals is the greater control man has acquired over his actions。 This quality of control； having been phylogenetically most recently acquired； is the most vulnerable to various NOCUOUS influences。 The result of a constant noci…integration may be a wearing…out of the control cells of the brain。 In a typical case of Graves' disease a marked morphologic change in the brain…cells has been demonstrated （Fig。 15）。 As has been previously stated； the origin of many cases of Graves' disease is associated with some noci…influence。 If this influence causes stimulation of both the brain and the thyroid； its excessive action may cause impairment of the brain and also hyperplasia of the thyroid。 As self…control is impaired； fear obtains an ascendency and； _pari passu_； stimulates the thyroid still more actively （Fig。 16）。 Finally； the fear of the disease itself becomes a noci…stimulus。 As the thyroid secretion causes an increase in the facility with which nervous energy is discharged； a pathologic reciprocal interaction is established between the brain and the thyroid。 The effect of the constantly recurring stimulus of the noci…influence is heightened by summation。 This reciprocal goading may continue until either the brain or the thyroid is destroyed。 If the original noci…stimulus is withdrawn before the fear of the disease becomes too strong； and before too much injury to the brain and the thyroid has been inflicted； a spontaneous cure may result。 Recovery may be greatly facilitated by complete therapeutic rest。 A cure implies the return of the brain…cells to their normal state； with the reestablishment of the normal self…control and the restoration of the thyroid to its normal state； when the impulses of daily life will once more have possession of the final common path and the noci…influence will be dispossessed。 The discovery of the real cause of a given case of Graves' disease is frequently difficult because it may be of a painful personal nature。 Of extreme interest is the fact that； in the acute stage； the patient may be unable to refer to the exciting cause without exhibiting an exacerbation of the symptoms of the disease。 I presume no case should be regarded as cured until reference can be made to its cause without an abnormal reaction。 It has been established that in Graves' disease injury to any part of the body； even under inhalation anesthesia； causes an exacerbation of the disease。 Fear alone may cause an acute exacerbation。 These acute exacerbations are frequently designated 〃hyperthyroidism〃 and are the special hazard of operation。
In applying the principle of anoci…association in operations on patients with Graves' disease there is scarcely a change in the pulse； in the respiration； or in the nervous state at the close of the operation。 I know no remedy which can obviate the effect of the inflowing stimuli from the wound after the cocain＇*＇ has worn off。＇t＇ It is necessary； therefore；
Beats 70 80 90 100 110 120
Ether ******* ******** ******** ******** ********
N2O ******* ******** ******** ******** *
Anoci。 ******* ******** ******** ** not to venture too far in serious cases。 Since the adoption of this new method （anoci…association） my operative results have been so vastly improved that I now rarely regard any case of Graves' disease as inoperable； at least to the extent of contraindicating a double ligation （Fig。 17）。
＇*＇ See footnote； page 4。@@@
＇t＇ In later papers and in 〃Anoci…association〃 （Crile and Lower） methods of combating postoperative hyperthyroidism are fully discussed。
If we believe that； in accordance with the law of phylogenetic association； a continuous stimulation of both the brain and the thyroid gland； accelerated by summation； plays a role in the establishment of the pathologic interaction seen in Graves' disease； then it is but the next step to assume that if the nerve connection between the brain and the thyroid be severed； or if the lobe be excised and the patient reinforced by a sojourn in a sanatorium or in some environment free from former noci…associations； he may be restored to normal health； provided that the brain…cells； the heart； or other essential organs have not suffered irreparable damage。 There are still many missing links in the solution of this problem； and the foregoing hypotheses are not offered as final； although from the viewpoint of the surgeon many of the phenomena of this disease are explicable。
Sexual…Neurasthenia
The state of sexual neurasthenia is in many respects analogous to that of Graves' disease。 In the sexual reflexes； summation leads to a hyperexcitability by psychic and mechanical stimuli of a specific type which is analogous to the hyperexcitability in Graves' disease under trauma and fear； the explanation of both conditions is based on the laws of the discharge of energy by phylogenetic association and summation。 It would be interesting to observe the effect of interrupting the nerve impulses from the field of the sexual receptors by injections of alcohol； or by other agencies； so as to exclude the associational stimuli until the nervous mechanism has again become restored to its normal condition。 Interpretation of Some of the Phenomena of Certain Diseases of the Abdomen in Accordance with the Hypothesis of Phylogenetic Association
The law of phylogenetic association seems to explain many of the phenomena of certain lesions in the abdominal cavity。 The nociceptors in the abdomen； like nociceptors elsewhere； have been established as a result of some kind of injury to which during vast periods of time this region has been frequently exposed。 On this premise； we should at once conclude that there are no nociceptors for heat within the abdomen because； during countless years； the intra…abdominal region never came into contact with heat。 That this inference is correct is shown by the fact that the application of a thermocautery to the intestines when completing a colostomy in a conscious patient is absolutely painless。 One would conclude also that there are no touch receptors in the abdominal viscera； and therefore no sense of touch in the peritoneum。 Just as the larynx； the ear； the nose； the sole of the foot； and the skin have all developed the specific type of nociceptors which are adapted for their specific protective purposes； and w