CICATRIZATION OF WOUNDSCarrel, Alexis; Hartmann, Alice
doi: 10.1084/jem.24.5.429pmid: 19868052
1. A method for measuring the area of a wound not geometric in form is described. 2. The rate of cicatrization of a wound is greater at the beginning than at the end of the period of repair. It depends on the area rather than on the age of the wound. There is a constant relation between the size of a wound and the rate of cicatrization. The larger the wound the greater is the rate of cicatrization. Two wounds of different size have a tendency to become equal. 3. The rate is proportional to the area, but diminishes less rapidly than the area. 4. The process of contraction is the more important factor in the repair of a wound. Epidermization completes the work of contraction. After the wound is healed, the cicatrix as a rule expands. 5. The curve representing the diminution of the size of an aseptic wound while it cicatrizes is regular and geometric. Footnotes Submitted: 24 May 1916
CICATRIZATION OF WOUNDSDu Noüy, P. Lecomte
doi: 10.1084/jem.24.5.451pmid: 19868053
The cicatrization of sterile wounds may be studied in the same way as an ordinary physicochemical phenomenon. It is possible, therefore, to express the law of cicatrization by a mathematical equation as soon as an accurate measure of the wound can be obtained. By means of the equation, a curve is obtained which represents the theoretical evolution of the cicatrization of a wound. This curve, being an expression of what should happen on a normal wound, healing aseptically, on a normal man, is a daily point of comparison to what appears actually on the observed wound, and allows one to study accurately the fluctuations of cicatrization on a given individual, and the action of different dressings and antiseptic substances Footnotes Submitted: 24 May 1916
CICATRIZATION OF WOUNDSDu Noüy, P. Lecomte
doi: 10.1084/jem.24.5.461pmid: 19868054
The first article of this series showed that it was possible to express mathematically the phenomenon of cicatrization. The principal point consisted in determining by means of an equation, a constant, or index, characterizing each wound. The calculation had to be made for each patient for each wound, and required two observations, 4 days apart. The index having proved to be a continuous function of the size of the wound and of the age of the patient, of the form See PDF for Equation where S is the area, i the index, a a decimal exponent, and K a constant, it was then possible to draw a chart by means of which this index i could be obtained without calculation. The advantage of the new way of determining the index is, above all, that this index is a general, average, normal index, and no longer an individual index. Hence, the differences between the observed rate of cicatrization of man and the normal rate may give some indication of the general state of the patient. Another advantage is that the determination of the index is no longer controlled by the temporary accidents which may happen between the two observations of S and S' . Footnotes Submitted: 20 June 1916
THE PROPHYLAXIS OF WEIL'S DISEASE (SPIROCHÆTOSIS ICTEROHÆMORRHAGICA)Ido, Yutaka; Hoki, Rokuro; Ito, Hiroshi; Wani, H.
doi: 10.1084/jem.24.5.471pmid: 19868055
We have already described briefly the portals of entry and of excretion of the pathogenic spirochetes. We may mention here that we have twice prevented epidemics by disinfection of the ground and the removal of the inundated water in certain places in coal mines. In one mine 19 out of 50 workmen, and in another 9 out of 30 workmen came down with Weil's disease in about 2 weeks. We have already pointed out that the period during which the pathogenic spirochetes are excreted in the urine continues, as a rule, for 40 days, and that we must, therefore, apply disinfection for at least 40 days after the first appearance of the disease. Lately we have found that in 21 cases out of 24 the spirochetes were excreted in the urine for 40 days, in one case until the 42nd day, in one case until the 45th day, and in still another case until the 63rd day. Another important fact concerning the prophylaxis which has been brought out is that both house and ditch rats (brown) carry virulent Spirochæta icterohamorrhagæ , the causal spirochete of Weil's disease, in their kidneys. Miyajima has reported that field rats have the pathogenic organisms in their kidneys; he will report these findings in detail later. The spirochetes which he described are less virulent than ours. On his advice we have carefully examined house and ditch rats in the city and rats in the coal mines of Kyushu, where Weil's disease prevails, and found that 39.5 per cent carried highly virulent pathogenic spirochetes in their kidneys, thus confirming Miyajima's experiments. The kidneys were examined microscopically under the dark-field microscope, and in the cases in which we did not find the pathogenic spirochete, we made inoculations into guinea pigs. Thus we found Spirochæta icterohæmorrhagiæ microscopically in the kidneys or in the urine in 32.4 per cent, and by means of inoculation in 7 per cent, making a total of 39.5 per cent carrying the pathogenic organisms, out of a total number of 86 rats examined. In some instances, rats were made to bite guinea pigs and in two instances caused Weil's disease. Among fifty-five patients in our clinic, twelve were cooks; and in Europe many cases arise among butchers—indicating the relation of the disease to rats. Moreover, during the present year we observed two patients who acquired Weil's disease, one in 1 week, the other 8 to 9 days after they had been bitten by rats. These facts point to a relation between Weil's disease and rats. The infection is transmitted probably from rats to man by means of the urine of the rats, directly or indirectly. On the injection of 0.1 gm. of rat urine which contains Spirochæta icterohæmorrhagiæ into the peritoneal cavity of guinea pigs, the infection arises, while the injection of the liver or the blood of the rats into guinea pigs does not produce the typical disease. The finding that the kidneys of rats contain the pathogenic organisms of the disease is important from the point of view of prophylaxis. The large number of rats in the trenches of the European battle-fields suggests the possibility that many cases of Weil's disease may arise. We shall report on this point in more detail later. Footnotes Submitted: 27 June 1916
EXPERIMENTAL OBSERVATIONS ON THE PATHOGENESIS OF GALL-BLADDER INFECTIONS IN TYPHOID, CHOLERA, AND DYSENTERYNichols, Henry J.
doi: 10.1084/jem.24.5.497pmid: 19868057
1. The theory of the production of gall-bladder lesions in typhoid, by descending infection of the bile from the liver receives support from investigations with the common duct fistula method in the rabbit. More bacilli appear in the bile with increased doses and more gall-bladder infections are obtained by increased doses. More bacilli appear in the bile after mesenteric vein injection than after ear vein injection and more lesions result under the first condition. More bacilli appear in the bile after injection of the same dose in immunized animals than in normal animals and more lesions also result in immunized animals. In cholera and dysentery the same mechanism is suggested with the additional factor of a portal system septicemia. 2. After the appearance of microorganisms in rabbit bile, their fate is apparently largely determined by the antiseptic properties of the bile. 100 per cent infections cannot be secured by intravenous doses large enough to insure the presence of microorganisms in the bile. Rabbit bile in vitro may be antiseptic to the microorganisms considered. The antiseptic action is largely due to its alkalinity. It is apparently possible to protect the rabbit to some degree against gall-bladder infection by a previous injection of sodium bicarbonate. 3. Alkaline therapy is suggested in the prevention and cure of gall-bladder carriers. Footnotes Submitted: 24 July 1916
STUDIES ON THE BLOOD PROTEINSHurwitz, S. H.; Meyer, K. F.
doi: 10.1084/jem.24.5.515pmid: 19868058
The progress of an infection is usually associated with marked changes in the serum proteins. There may be an increase in the percentage of the total protein during some stage of the infection, and there is usually a change in the albumin-globulin ratio with an increase in the total globulins. This rise may antedate the development of any resistance by a considerable period of time. The non-protein constituents of the blood show fluctuations with a tendency to rise as the infection progresses. The process of immunization is in almost all instances associated with a definite increase in the globulins of the blood, and in some cases with a complete inversion of the normal albumin-globulin ratio. This may be produced both by living and dead organisms and by bacterial endotoxins. Massive doses usually result in an upset which shows no tendency to right itself during the period of observation. A rise in the globulins has been shown to occur long before the animal develops immune bodies in any appreciable concentration; and where the globulin curve and antibody curve appear to parallel one another, it can be shown by a careful analysis of both curves that there is a definite lack of correspondence at various periods of the experiment. Animals possessing a basic immunity show a more rapid rise in the globulin curve following inoculation. There is no parallelism between the leukocytic reaction and the globulin reaction. During periods of leukopenia the globulins may be as high as during the period of a leukocytosis. Bacterial endotoxins produce as striking an increase in the serum globulins as do living and killed bacteria. This would seem to indicate that a bacterial invasion of the organism is not absolutely essential for the globulin changes, and that the toxogenic factor in infection and immunity must play a part in the production of the changes noted. Inflammatory irritants injected intraperitoneally also result in a globulin increase. In this case the changes produced may best be explained by the toxogenic effect produced by the protein split products resulting from the inflammatory condition. Intraperitoneal injections of killed bacteria give rise to a more rapid increase in the serum globulins. The rapidity of the response following intraperitoneal as compared with intravenous injections doubtless stands in intimate relationship to the neutralizing power possessed by the blood serum and perhaps to the more extensive surface of absorption following injection by the intraperitoneal route. Footnotes Submitted: 12 August 1916
THE RELATION BETWEEN THE THYROID AND PARATHYROID GLANDSTanberg, Andreas
doi: 10.1084/jem.24.5.547pmid: 19868059
The following conclusions may be drawn from the experiments presented in this article. 1. Excessive meat diet develops hypertrophy of the thyroid gland. A definite hypertrophy of the parathyroid gland under the same conditions has not been established. A meat diet does not develop hypertrophy of the thyroid gland when insufficiency of the parathyroid gland exists at the same time, even if no clinical symptoms are present. Where a pronounced hypertrophy caused by a meat diet has already developed, the hypertrophy disappears and the gland assumes its ordinary appearance after extirpation of a sufficiently large number of parathyroid glands. 2. After parathyroidectomy no hypertrophy of the thyroid gland takes place. In chronic tetany the thyroid gland seems, on the contrary, to atrophy in spite of a meat diet. 3. After complete extirpation of the thyroid gland, the parathyroid gland does not change its structure, even in cases where the cachexia lasts for several years. Small remaining parts of the thyroid gland may through hypertrophy develop into compact tissue and thereby seemingly present some points of resemblance to the parathyroid gland. 4. When the parathyroid gland hypertrophies, as in some forms of chronic tetany, this hypertrophy is characterized by the development of large, transparent, sharply defined cells, with large nuclei rich in chromatin. 5. The parathyroid and thyroid glands are independent organs, each having specific functions. This, however, does not exclude the occurrence of a direct or indirect interaction in the functions of the two systems. 6. There is reason to believe that an insufficiency of the parathyroid gland checks to some extent the function of the thyroid gland. No proof of the existence of a vicarious cooperation between the two glands has been established. Footnotes Submitted: 13 January 1916
STUDIES ON TREPONEMA PALLIDUM AND SYPHILISZinsser, Hans; Hopkins, J. G.; McBurney, Malcolm
doi: 10.1084/jem.24.5.561pmid: 19868060
1. Immune sera produced in rabbits by treatment with our Culture Strain A of Treponema pallidum agglutinated not only the homologous strain, but also the Noguchi strains, and indicate a close group relationship of other non-pathogenic treponemata. Absorption experiments confirmed this, indicating a close relationship between the pallidum and the calligyrum . 2. Culture treponemata are not agglutinated to a much greater extent by the sera of syphilitic rabbits than they are by those of normal rabbits. 3. Culture treponemata are not agglutinated to any considerable extent by the sera of rabbits immunized with virulent treponemata. 4. The sera of syphilitic patients, especially those in the tertiary stages, agglutinate culture pallidum to a slightly greater extent than do those of normal individuals, but the culture pallidum is agglutinated to an almost equal degree by the sera of many individuals with diseases other than syphilis. We do not think that we could definitely distinguish the syphilitic from the non-syphilitic serum by the agglutination of the culture pallida , and therefore we do not believe that the reaction has any diagnostic value at present. 5. Immunization with culture pallidum , either general or local, does not seem to confer upon rabbits any considerable degree of resistance to inoculation with virulent treponemata. 6. Rabbits that have once exhibited lesions in the testis are not easily reinfected at the same site if reinoculation is practiced more than a month or so after apparent healing of the lesion. We believe that the experiments above recorded strongly suggest that resistance to syphilis in rabbits is a localized cell phenomenon not dependent upon a generalized reaction on the part of tissues remote from the site directly involved in reaction with the invading treponemata. Antibodies analogous to those formed in most bacterial infections appear in the general circulation in slight amount, if at all. The finding of many motionless treponemata in a few of the small lesions following reinoculation suggests the possibility of a purely localized formation of antibodies. This was expressed by Landsteiner some years ago when he spoke of the localized formation of agglutinins when they were absent in the general circulation. We hesitate to apply these results too generally to the conditions prevailing in human syphilis, but they contain the possibility of an explanation for the apparent skin immunity of the secondary period, and the later successive involvement of some organs and tissues when others remain normal and when external superinfection is successfully resisted. Footnotes Submitted: 26 June 1916