We have studied these defense reactions for trauma, the degree of intensity of the trauma indicating the extent of the exogenous heterogenization. Very intensive trauma can produce a lethal superacute shock which corresponds, as we shall see below, to a generalized primary response. A less intensive trauma may induce a tissular necrosis with consecutive sloughing as a localized primary defense. A still less intensive trauma may induce an allergic tissular response. The importance of these changes for clinical manifestations is such that it appears necessary to emphasize them. After surgery, for instance, a slight temperature elevation is often observed between the 7th and 9th day. This has to be interpreted as an allergic reaction. When intensive enough, this allergic response with the ensuing lytic action passes from the tissular level to the higher level of the blood vessels. Along with inflammation and pain, local hemorrhages often appear. Severe hemorrhages occur at this time after various traumatic incidents. The most disturbing complications for plastic surgery of the nose, for instance, are the severe "7th day hemorrhages." The fact that they start at this critical moment indicates their allergic pathogenesis. The study of these allergic changes has shown that they occur in the evolution of all traumatic lesions. They can occur and remain clinically inapparent and uneventful, as seen in the following experiment.

In groups of rats of the same sex and age kept under similar conditions, parallel skin incisions 3 cm. long at 1/2 cm. intervals were made. The lesions were excised at different times and chloride content determined. Fig. 78 shows the curve of average values of the total chloride content of these skin wounds in groups of six animals for each day. It can be seen that intensive local chloride retention occurs with the first defense reaction, with values as much as four times greater than those of normal tissues. On the third day, chloride content falls. It goes below normal tissue values after the fifth day during the healing process. However, in an otherwise regular curve, there is a distinct temporary increase in chloride content on the 8th day. Its occurrence at this time, when coagulant antibodies appear, indicates its allergic nature.

The same allergic pathogenesis explains the exacerbation of symptoms seen about the 7th day in many conditions. In patients who have suffered a myocardial infarct, for example, recurrence of pain is often seen the 7th-8th day after the infarct.

Part of the effects of chemical, physical and hormonal agents could be interpreted in terms of influence exerted upon the different factors which intervene in the defense mechanism. Some agents such as opium derivatives were seen to affect the liberation of hydrolytic enzymes while others interfere with the manufacture of allergic or immune antibodies. The influence exerted by radiation upon the defense mechanism can be related to its effect upon granulocytes and lymphocytes while neoglucogenic corticoids affect the connective tissue and lymphocytes.

Wound chloride curve

Fig 78. Wound chloride curve. The curve of the amount of the chlorides present in skin wounds in rats corresponds to the average value obtained in 6 rats for each figure. A first phase, with high values corresponds to the offbalance D. This is followed by a second phase characterized by an offbalance A. A variation in the curve corresponding to the 8th day is constantly seen as corresponding to an allergic reaction. The values represent mgs. of chlorine per 100 gr. of weight of the wet material.

Research in all these directions is still in progress and the results will be communicated in further publications.

For the time being, they have brought more information and suggestions of research in the special case of the immunological problem of cancer.