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overwork or of fear with the sexual development of maturing girls is obviously favorable to the incidence of Graves’ disease. The presence of a colloid goiter is a suitable soil for the development of Graves’ disease, and I fully recognize also the evidence that infection or autointoxication may be contributing factors and must be assigned their role.

 

I have never known a case of Graves’ disease to be caused by success or happiness alone, or by hard physical labor unattended by psychic strain, or to be the result of energy voluntarily discharged.

Some cases seem to have had their 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 which, when adequately stimulated, respond in a specific manner in accordance with the law of phylogenetic association, so, the abdominal viscera have developed equally specific nociceptors as a protection against specific nocuous influences. The principal harmful influences to which the abdominal viscera have been exposed during vast periods of time are deep tearing injuries by teeth and claws in the innumerable struggles of our progenitors with each other and with their enemies (Fig. 9); peritonitis caused by perforations of the intestinal tract from ulcers, injuries, appendicitis, gall-stones, etc.; and overdistention of the hollow viscera by various forms of obstruction.

Whatever may be the explanation, it is a fact that the type of trauma which results from fighting corresponds closely with that which causes the most shock in the experimental laboratory.

Division of the intestines with a sharp knife causes no pain, but pulling on the mesentery elicits pain. Ligating the stump of the appendix causes sharp, cramp-like pains. Sharp division of the gall-bladder causes no pain, but distention, which is the gall-bladder’s most common pathologic state, produces pain.

Distention of the intestine causes great pain, but sharp cutting or burning causes none. In the abdominal viscera, as in the superficial parts, nociceptors have presumably been developed by specific harmful influences and each nociceptor is open to stimulation only by a stimulus of the particular type that produced it.

 

As a result of the excitation of nociceptors, with which pain is associated, the routine functions, such as peristalsis, secretion, and absorption are dispossessed from the control of their respective nervous mechanisms, just as they are inhibited by fear. This hypothesis explains the loss of weight, the lassitude, the indigestion, the constipation, and the many alterations in the functions of the various glands and organs of the digestive system in chronic appendicitis.

It readily explains also the extraordinary improvement in the digestive functions and the general health which follows the removal of an appendix which is so slightly altered physically that only the clinical results could persuade one that this slight change could be an adequate cause for such far-reaching and important symptoms.

This hypothesis explains certain gall-bladder phenomena likewise,—

indigestion, loss of weight, disturbed functions, etc.,—and it may supply the explanation of the disturbance caused by an active anal fissure, which is a potent noci-associator, and the consequent disproportionate relief after the trivial operation for its cure.

Noci-association would well explain also the great functional disturbances of the viscera which immediately follow abdominal operations.

 

Postoperative and traumatic neuroses are at once explained on the ground of noci-association, the resulting strain from which, upon the brain-cells, causes in them physical lesions.

If one were placed against a wall and were looking into the gun muzzles of a squad of soldiers, and were told that there were nine chances out of ten that he would not be killed outright when the volley was fired, would it help him to be told that he must not be afraid?

Such an experience would be written indelibly on his brain.

This corresponds closely to the position in which some surgical patients are placed. In railway wrecks, we can readily understand the striking difference between the after-effects in the passengers who were conscious at the time of the accident and those who were asleep or drunk.

In the latter the noci-perceptors and receptors were not aroused, hence their immunity to the nervous shock. In the functional disturbances of the pelvic organs, association and summation may play a large role.

On this hypothesis many cases of neurasthenia may well be explained.

From the behavior of the individual as a whole we may well conclude that summation is but a scientific expression for “nagging.”

Many other pathologic phenomena may be explained in a similar manner.

Thus we can understand the variations in the gastric analyses in a timid patient alarmed over his condition and afraid of the hospital.

He is integrated by fear, and as fear takes precedence over all other impulses, no organ functionates normally. For the same reason, one sees animals in captivity pine away under the dominance of fear.

The exposure of a sensitive brain to the naked possibility of death from a surgical operation may be compared to uncovering a photographic plate in the bright sunlight

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