Showing papers in "Journal of Experimental Medicine in 1918"

Spirilla associated with disease of the fetal membranes in cattle (infectious abortion).

Abstract: Spirilla of identical morphological and cultural characters have been isolated in pure culture from the fetuses of fourteen cases of abortion. The condition of the fetus is much the same whether spirilla or the bacilli of abortion are present. This condition is probably due in both cases to interference with the placental circulation. The injurious action of the etiological factor when spirilla are present is limited to the fetal membranes, more particularly the chorion. Definite lesions of the fetus were not detected. The spirilla gain access to the digestive and respiratory organs of the fetus when the latter swallows the amniotic fluid. More rarely they are disseminated through the body, probably through the circulation. The spirilla will grow in certain culture media only under reduced oxygen tension, readily secured by sealing the ordinary culture tubes with sealing wax. Laboratory animals (mammals) are refractory. The precise relation of the spirillum to the pathologic process remains to be more definitely formulated. Since the spirillum was first isolated, twenty-seven cases have been found associated with Bacillus abortus and fourteen with the spirillum. In none was a mixed infection with both organisms detected. The spirillum has been isolated only from the second or succeeding pregnancies. Table I summarizes the data collected thus far. It gives by. number the male and shows that the spirillum is not associated with any one bull. The spirillum has been found in fetuses of various ages as shown in Column 3. The distribution of spirilla as shown by cultures is given, the sign + indicating pure cultures, the sign no growth. The guinea pig inoculations are shown to be uniformly negative as regards Bacillus abortus.

The relation of circulating antibodies to serum disease.

Abstract: 1. The injection of horse serum either in small or in large amounts in human beings is always followed sooner or later by the development of hypersensitiveness of the skin to subsequent injections of horse serum. For the development of this reaction serum disease is not essential. 2. The blood serum of most patients who suffer from an attack of serum disease following injections of horse serum shows anaphylactin and precipitin for horse serum. 3. Anaphylactin and precipitin cannot be demonstrated in the blood serum of patients treated with horse serum who do not later present symptoms of serum sickness. 4. The appearance of anaphylactin and precipitin precedes shortly recovery from the disease. 5. With the appearance in the serum of antibodies to horse serum in great concentration, the antigen rapidly diminishes or disappears. 6. It is probable that the extrusion of these antibodies into the circulation is the result and not the cause of serum sickness. Their presence serves to neutralize or destroy the antigen and thus determines the recovery from serum sickness.

Morphological Characteristics and Nomenclature of Leptospira (Spirochaeta) icterohaemorrhagiae (Inada and Ido).

Abstract: The present study deals with the morphology and systematic position of the causative agent of infectious jaundice. There are several features which are not found in any of the hitherto known genera of Spirochaetoidea which led me to give this organism an independent generic name, Leptospira, denoting the peculiar minute elementary spirals running throughout the body. The absence of a definite terminal flagellum or any flagella, and the remarkable flexibility of the terminal or caudal portion of the organism are other distinguishing features. Unlike all other so called spirochetes the present organism resists the destructive action of 10 per cent saponin. A detailed comparative study of related genera, including Spirochaeta, Saprospira, Cristispira, Spironema, and Treponema, has been given with the view of bringing out more strongly the contrast between them and the new genus. A study has been made to discover whether any differential features exist among the strains of Leptospira icterohaemorrhagiae derived from the American, Japanese, and European sources, but none has been found. It is hoped that the creation of a new genus may facilitate a more exact morphological description than has hitherto been possible, due to the vague use of the term Spirochaeta which indiscriminately covered at least six large genera of spiral organisms.

Studies of lung volume. i : relation between thorax size and lung volume in normal adults

Abstract: On page 65, Vol. XXVII, No. 1, January 1, 1918, the last two sentences of the second paragraph should read: The difference between the total capacity and the middle capacity (all that can be breathed in after a half expiration) is called the "complementary air."2 The difference between middle capacity and residual air (all that can be breathed out after a half expiration) is called the "reserve air."

Behavior of hypochlorite and of chloramine-t solutions in contact with necrotic and normal tissues in vivo

Abstract: 1. The fall in chlorine concentration of Dakin's hypochlorite solution is more rapid in contact with necrotic than in contact with normal tissue. 2. The fall in chlorine concentration of chloramine-T solution is very slight when applied to necrotic tissue and is negligible when applied to normal tissue. 3. The action of the hypochlorite solution on tissue results in the separation of particles of necrotic tissue, hair, epithelial scales, coagulated serum, etc., and a gradual digestion of these substances, taking place over a period of at least 17 hours. 4. The fall in the chlorine concentration of the hypochlorite solution is not complete until the particles are completely dissolved. 5. Chloramine-T solution, 2 per cent, has no erosive effect comparable with that exhibited by the hypochlorite solution. 6. Repeated exposures to the three solutions show the hypochlorite solution to be superior in its cleansing ability on necrotic tissue. 7. The hypochlorite solution is much more irritating to normal rabbit skin than chloramine-T solution or the alkaline control solution. 8. Therefore, the irritating effects must be due to the readily available chlorine.

Modifications of Culture Media used in the Isolation and Differentiation of Typhoid, Dysentery, and Allied Bacilli.

Abstract: The three media as modified—Endo medium, neutral red-brilliant green, and the lead acetate Russell double sugar—have proved in our hands the best combination for the isolation and rapid differentiation of the various organisms belonging to the typhoid-dysentery group of bacilli.

A study of the antiseptic properties of certain organic compounds.

Abstract: This study of the inhibitive effect of aniline and some of its derivatives and of the triphenylmethane dyes on certain bacteria warrants the following tentative conclusions: 1. The composition and reaction of the medium exert a marked influence on the behavior of the antiseptic. The higher the concentration of organic nitrogenous compounds (peptone) in the medium, the lower is the effective concentration of the dye. The reaction of the medium modifies the specific action of the antiseptic, owing probably to an alteration in the bacterial cell. 2. The germicidal action of the compounds is a function of the benzene nucleus, the added elements or radicals, their number, and, in the case of the dyes, probably the quinoid structure of the nucleus. 3. As far as tested, the increase in the number of alkyl radicals increases the antiseptic power. Methyl green is an interesting exception to this rule, for the change of one of the nitrogens to the quaternary salt is accompanied by an almost complete loss in inhibitive action. 4. The antiseptic power is enhanced to a greater extent by an ethyl than a methyl group, and the second alkyl produces a proportionately greater increase than the first. It appears that the relative position of the introduced group may be a factor in determining the relative improvement in the effectiveness of the compound. 5. The introduction of a methyl group in the nucleus consistently enhances the inhibitive action of the compound and its alkyl derivatives. This is evident from a comparison of the action of aniline and its derivatives with that of toluidine and its corresponding derivatives. 6. The simple aniline derivatives, as well as the dyes, are more toxic for the Gram-positive than the Gram-negative bacteria. Of the former, Bacillus subtilis is more sensitive to the dyes than Staphylococcus aureus, while the reverse is true in the case of the aniline compounds. 7. The most marked specific selective effect is manifested by the triphenylmethane dyes. Bacillus aerogenes and Bacillus typhosus possess a higher resistance to these substances than Bacillus coli or Bacfflus dysenterice. The last is exceedingly sensitive. This partial specificity is apparently a function of the molecule as a whole.

The survival of leptospira (spirochæta) icterohæmorrhagiæ in nature; observations concerning microchemical reactions and intermediary hosts

Abstract: 1. Leptospira icterohaemorrhagiae is unable to grow in the urine, either with or without the addition of suitable culture ingredients, the acidity of the urine being detrimental to the growth. It survives less than 24 hours, unless the urine is neutralized or slightly alkalized, when the period of survival is somewhat longer. If suitable nutrient ingredients are added to the neutralized or slightly alkalized urine, the organism is able to grow for about 10 days, after which multiplication ceases. 2. Feces from normal or jaundiced persons destroy Leptospira icterohaemorrhagiae within 24 hours when a rich culture is added and the mixture allowed to stand at 26 degrees C. The addition of blood serum and corpuscles does not prevent the destruction of the organism. Autoclaved specimens and filtrates of unheated feces do not constitute a suitable medium in which to keep the organism alive for any length of time, but the addition of blood corpuscles and serum in adequate quantities renders them fairly satisfactory as media. Under natural conditions Leptospira icterohaemorrhagiae cast off in the feces cannot survive more than 24 hours. 3. Polluted water, sewage, and soil will not serve to keep Leptospira icterohaemorrhagiae alive for more than 3 days at the most. When deprived by filtration or autoclaving of their bacteria they become indifferent diluents and may be used to make up a culture medium when mixed with serum and citrate plasma of a suitable animal. Sterilized soil with a neutral reaction, when added to a culture, has an unfavorable effect upon the growth of the organism. 4. Most of the aerobic bacteria found in feces, sewage, soil, and tap water inhibit the growth of Leptospira icterohaemorrhagiae when inoculated into the same medium. Bacillus faecalis alkaligenes and many strains of non-hemolytic streptococci caused the least interference, although growth was never so vigorous or lasting in the media in which they were present as in the control media. Certain pathogenic bacteria (Bacillus typhosus, Bacillus paratyphosus, Bacillus dysenteriae, pneumococcus) are antagonistic to the growth of the spirochete. 5. Leptospira icterohaemorrhagiae is highly sensitive to the destructive action of bile, bile salts, and sodium oleate, but resists the action of saponin. In this last respect it differs from many so called spirochetes. The destructive action of these agents is counteracted by blood serum. 6. The larvae and adults of the Culex mosquito, the larvae of the house-fly and bluebottle fly, wood ticks (Dermacentor andersoni), and leeches failed to become carriers of the spirochetes when fed on infected guinea pigs or their organs; that is, they cannot play the part of an intermediary host of Leptospira icterohaemorrhagiae.

Studies of lung volume : ii. tuberculous men.

Abstract: 1. The total capacity, middle capacity, and residual air have been determined in 31 adult male patients suffering from tuberculosis of the lungs. 2. The chest volumes have been determined in each case and the normal lung volumes calculated by means of the ratios worked out in a previous paper. 3. In nine patients with incipient tuberculosis, the total lung volume was found within normal limits, whereas the vital capacity was diminished as a result of an increased residual air. The increase in the residual air was due to less complete expiration, caused partly by diminished movement of the diaphragm, partly by diminished compression of the chest wall. The diminished movement of the diaphragm was, as a rule, most marked on the most affected side. Whether these decreased movements are due to a reflex or to stiffness of the lung tissue we could not determine. The middle capacity was found practically normal. 4. In twenty-two cases of moderately advanced, and advanced tuberculosis, the total lung volume was in most cases markedly decreased. The vital capacity was substantially decreased, principally as a result of the diminished total capacity. The residual air was, as a rule, normal, although in a few cases an increase in residual air also contributed to the decrease in the vital capacity. The middle capacity, on which we do not want to put too much stress, was normal in some patients and considerably diminished in others.

The lymphocyte in natural and induced resistance to transplanted cancer iii. the effect of x-rays on artificially induced immunity.

Abstract: Mice artificially immunized against a transplantable carcinoma, inoculated, and proved immune, may be again rendered susceptible to the same tumor by exposure to the x-rays. The immune animals which have not been treated with the x-rays preserve, to a large degree, their resistance to a second inoculation of the tumor in question.

Results of prophylactic inoculation against pneumococcus in 12,519 men.

Abstract: 1. From a study of the agglutinins and protective power of the serum of 42 persons vaccinated against the pneumococcus, Types I, II, and III, it is demonstrated that a definite immune response has been secured to Types I and II by the dose of vaccine employed. Little evidence of response to Type III can be demonstrated by these methods, but this is of less significance in that in animals it is relatively difficult to secure antibodies against this strain in the serum, even though a considerable degree of active immunity may have been produced in the vaccinated animal. 2. The degree of response to the vaccination appears to be dependent upon the total dosage of each type of pneumococcus administered. While some response may be elicited by 2(1/2) billion cocci of each type, a much more constant and greater response follows 13 billion. 3. In subcutaneous administration the manner in which the total dosage is divided, whether given in a single large dose, in seven small daily doses, or in three to five moderate doses at 3 to 7 day intervals, seems to have little influence upon the degree of immune response, provided the total dosage is the same. 4. The local and general toxic reaction varies greatly in different individuals. The smaller the individual doses, the fewer are the severe reactions. This makes it desirable to divide the total dosage into as many inoculations as circumstances make practicable. 5. At Camp Upton 12,519 men have been vaccinated against Pneumococcus Types I, II, and III. Three or four doses were given at intervals of 5 to 7 days with a total dosage of 6 to 9 billion of Types I and II and 4(1/2) to 6 billion of Type III. 6. During the 10 weeks that have elapsed since the vaccination, no cases of pneumonia of these three types have occurred among the men who had received two or more injections of vaccine. 7. In a control of approximately 20,000 men there were twenty-six cases of Pneumococcus Types I, II, and III pneumonias during the same period. 8. The incidence of Pneumococcus Type IV pneumonia and streptococcus pneumonia was much less among the vaccinated troops than among the unvaccinated. No explanation has been advanced for this difference. 9. Small sterile infiltrations disappearing spontaneously occasionally follow the injection of large doses of pneumococcus vaccine and appear to be an expression of cutaneous hypersusceptibility. 10. The persons who develop these lesions exhibit local reactions to each dose of vaccine. They also give abnormally marked reactions to intradermal injections of pneumotoxin. They do not, however, exhibit anything notable in the agglutinative or protective powers of their sera after vaccination. Whereas the immune response is characteristically specific for the type of pneumococcus, this reaction is not specific for any type. We have found no evidence that Type III is more prone to elicit these severe local reactions than are Types I and II. 11. Prophylactic vaccination against pneumococcus of Types I, II, and III is practical and apparently gives protection against pneumonia produced by these types. It remains to be determined how long this immunity persists.

The effect of injections of hemolytic streptococci on susceptible and insusceptible animals

Abstract: 1. Streptococci injected into the circulation of cats are quickly withdrawn and are found most numerously in the lung, less numerously in the liver and spleen, and in small numbers in the bone marrow, lymph nodes, muscle, and kidney. 2. The streptococci taken up by the lung are killed within 5 to 8 hours, although they remain visible in films for a number of days. In the liver they are killed less rapidly, and in the spleen a few may remain viable for a considerable period. 3. This bactericidal action may be demonstrated in pieces of excised lung but not in lung extracts, and is apparently dependent on the action of the living cell. 4. Streptococci injected into a susceptible animal, the rabbit, are also promptly removed from the circulation, but are distributed in different proportions, the liver and spleen absorbing almost as many as the lung, and the muscles also taking up an appreciable number. 5. As in the cat, the organisms taken up by the lung and liver of the living rabbit are promptly killed. Those which lodge in the muscles, however, multiply rapidly. 6. About the time that the streptococci have begun to develop in the muscles (4 to 8 hours after injection) the number in the blood stream begins to increase. 7. The increase in the blood stream is not due to exhaustion of the mechanism of their removal nor have these organisms acquired a resistance sufficient to maintain them in the blood stream of a normal animal. The septicemia, then, is probably the resuit of washing out of organisms from the infected tissues. 8. Attempts to immunize rabbits have been unsuccessful, but in certain treated animals the distribution of the organisms among the various organs approached that found in insusceptible animals; i.e., cats.

Urinary siderosis : hemosiderin granules in the urine as an aid in the diagnosis of pernicious anemia, hemochromatosis, and other diseases causing siderosis of the kidney.

Abstract: In diseases which bring about a siderosis of the kidney there are ordinarily present in the urinary sediment cells containing granules of hemosiderin, and often many free granules as well. The finding has proved useful in the diagnosis of hemochromatosis and will probably be of service in the recognition of pernicious anemia, and possibly some other diseases. But in this relation the fact should be emphasized that urinary siderosis, as one may term it, is the indication of a renal condition, not of a disease.

Further investigations on the origin of tumors in mice : v. the tumor rate in hybrid strains.

Abstract: 1. In order to test our previous conclusions concerning the tumor rate in hybrid strains, we carried out additional hybridizations. For this we selected strains which differed markedly in their tumor rate and which had been followed through a number of generations and found constant in their behavior. Hybridizations between strains or families of a similar (either high, medium, or low) tumor rate served as control experiments. In these cases the offspring showed a tumor rate similar to that of the parents. 2. In selecting for hybridization various groups of Cream mice representing a very low tumor strain and English Sable mice representing a high tumor strain, we obtained in the majority of cases hybrid strains with a tumor rate intermediate between that of both parent strains. In a few instances it approached somewhat the high tumor strain of the English, and in a few others the low tumor rate of the Cream. 3. In several hybrids between the high tumor strain English and the low tumor strain Silver, the latter of which was split off from the English, the high tumor rate of the English prevailed. A number of mice which served for hybridization were followed throughout their life and found to behave typically as to tumor rate. 4. If we omit the strains in which both parents had a similar tumor rate, we found the higher tumor rate to be dominant in twenty-four hybrids. In seventeen of these the mother strain dominated, and in seven the father strain. In nineteen hybrid strains the tumor rate was intermediate. In ten strains the lower tumor rate dominated. In eight of these the mother strain prevailed and in two the father strain. The low tumor rate was, therefore, dominant in approximately 18 per cent of the strains. 5. There does not seem to be a fixed rule as to dominance in the tumor rate. In a considerable number of cases, and especially in well analyzed cases, the result was intermediate. 6. Altogether in twenty-five of our hybrid strains the mother strain, and in nine strains the father strain prevailed. In nineteen strains the result was intermediate. We conclude that both father and mother strain may dominate and that the tumor rate is not in the strict sense of the term a sex-linked character. However, the fact that the mother strain prevailed in a much larger number of our cases than the father strain, and that several times (but not in all cases), in reciprocal crosses, the hybrids followed the tumor rate of the mother strain, suggests the possibility that as far as the hereditary transmission of mammary cancer in mice is concerned, the mother may be more potent than the father, and that perhaps under certain quantitatively varying conditions the mother strain may dominate over the father strain. This statement is merely a tentative conclusion at the present time and needs further investigation. 7. The results of these investigations confirm our previous conclusion that in the majority of the crosses which we observed, the cancer rate is either intermediate between those of father and mother strain, or that it follows the tumor rate of the parent with the higher rate and only in a relatively small number of instances the cancer rate follows that of the parent strain with the lower tumor rate. On the whole, the heredity of cancer rate and cancer age follows the blending type of hereditary transmission. 8. While there is a distinct relation between high tumor rate and early cancer age, our observations make it probable that cancer rate and cancer age are to some extent independent of each other. 9. On the whole the different generations, including F1 and F2 of the various hybrid strains, showed a concordant tumor rate and tumor age. 10. If we consider, then, our results as a whole, we may conclude that in crossing strains which differ in their tumor rate no rule of dominance which applies equally to all cases seems to exist. In a certain number of crosses the results are undoubtedly intermediate. In these instances the tumor rate and to some extent also the tumor age behaves in a manner similar to characters which differ in father and mother merely in quantity as in the length of organs. From such intermediate results all kinds of gradations exist, leading on one side to dominance of the strain with the higher tumor rate and on the other side to dominance of the strain with the lower tumor rate. However, in our experiments dominance of the strains with the higher tumor rate greatly predominated over the opposite extreme. 11. Our results on the whole are, therefore, in certain respects comparable with the inheritance of sex which Goldschmidt studied in hybrid strains of the gypsy mother. Here also all gradations from the male to the female were observed in the offspring. Goldschmidt assumes that in different hybrids there are created different quantities of certain substances which like enzymes determine according to their quantity the velocity of chemical reactions and the amount of certain substances produced. The latter determine in the hybrids the quantitative variations in the character which is analyzed. According to Goldschmidt, multiple allelomorphs, which in our experiments seem to determine the heredity of spontaneous cancer, depend upon differences in the quantity of a substance present in the different individuals or varieties. In whatever way we may conceive of the character of multiple allelomorphs, our results make it probable that multiple factors are involved in the heredity of cancer in mice.

Studies on x-ray effects : i. destructive action on blood cells.

Abstract: 1. X-rays in large doses affect the lymphocytes before any of the other circulating cells. 2. There is a sharp fall in the total number of circulating lymphocytes, which is complete 48 hours after x-ray treatment. 3. Following the immediate decrease in the circulating lymphocytes there is a primary rise, followed by another fall, which in turn is followed by a permanent rise of these cells to normal. 4. The effect of the x-rays on different species of animals varies considerably, but in those studied, cat, monkey, guinea pig, rabbit, rat, mouse, and pony, the selective action on the lymphocytes was in all instances apparent. 5. When several animals of the same species are given the same dose of x-rays, the effect on the circulating lymphocytes seems to be quantitatively parallel, when determined by blood counts. 6. The polymorphonuclear neutrophilic leucocytes, when affected at all, increase in number immediately after the administration of the x-rays and then tend to decrease below their normal level. This decrease is followed by a return to normal many days before the lymphocytes reach their original level. 7. The other cells of the blood follow the neutrophilic curve. 8. Percentage figures, as determined by differential blood counts, do not give an accurate indication of the effect of the x-rays. It is only when these are multiplied by the total white blood count that a figure, representing the total number of cells of the series per c. mm. of blood, is obtained, which varies to the stimulus in a constant manner, the variations being practically quantitative.

Studies of oxygen in the venous blood ii. studies of the oxygen unsaturation in the venous blood of a group of patients with circulatory disturbances.

Abstract: 1. Thirty-one determinations of the total oxygen-combining power and the oxygen in the venous blood from vena mediana cubiti of sixteen resting patients are reported. 2. The difference between the total oxygen capacity of the hemoglobin and the oxygen in the venous blood, the oxygen unsaturation, is calculated. 3. In twelve patients with compensated heart lesions the unsaturation was found within normal limits, between 2.5 and 8 volume per cent. 4. In four patients with incompensated heart disease the values for the unsaturation were all above the normal limit, from 9.7 to 15.2 volume per cent. 5. A general discussion of the problem of interpreting the results is given. 6. A comparison is drawn between the oxygen consumption calculated from direct determination of the blood flow on a normal subject (the writer) and the oxygen unsaturation determined 4 years later on the same subject. A close agreement between the two series of values exists.

The optimum hydrogen ion concentration for the growth of pneumococcus.

Abstract: 1. The optimum hydrogen ion concentration for the growth of the various types of pneumococcus is a pH of about 7.8. 2. The limiting hydrogen ion concentrations for the growth of pneumococcus are a pH of 7.0 and a pH of 8.3. 3. Phosphates used in adjusting reactions of media retard growth if present in a concentration greater than 0.1 molecular. 4. Culture media for pneumococci should, therefore, have an initial reaction between a pH of 7.8 and 8.0 and a total salt concentration not exceeding 0.1 M.

Free antigen and antibody circulating together in large amounts (hemagglutinin and agglutinogen in the blood of transfused rabbits).

Abstract: In rabbits transfused almost daily with the whole citrated blood of other rabbits, an extraordinary condition often develops, which manifests itself in an almost immediate clumping together of all the red cells in specimens of the shed blood. This clumping is due to one or more true agglutinins, of which the strength may be such as to cause clumping in a 1: 2,800 plasma dilution. The agglutinating principle circulates with the corpuscles against which it is effective; but under ordinary circumstances intravascular clumping fails to occur because the union of antigen and antibody can take place only at a temperature several degrees below that of the body. If the temperature is sufficiently lowered, as when a tourniquet is applied to the rabbit's ear, intravascular clumping ensues. In defibrinated blood, gradually cooled, clumping is first noted as the temperature of 35°C. is approached; and at room temperature (22°) the corpuscles will often come together in a short time into a single, solid mass. At 0°C. the agglutination is still more marked. The reaction seems to be completely reversible, for when the blood is warmed again, the clumps break up and disappear at between 35° and 36°C. Cooling and warming with the resultant clumping and dissociation can be carried out many times on the same blood specimen without apparent change in the corpuscles or in the rapidity of the reaction. The response to temperature changes is extremely prompt. Once it has been elicited, the agglutinating principle may persist for a long time after the transfusions are stopped, in one instance it was still strong 133 days after the last transfusion. During this period the plethora was succeeded by a severe anemia, which in turn was recovered from. In many rabbits no agglutinin develops, and a continuance of the transfusions will not elicit it. Indeed, when present it tends to disappear if the transfusions are persisted in. In several of the animals in which the agglutinin was strongest, the plethora was suddenly succeeded by severe anemia, despite continued transfusions. The character of the temperature control of the agglutination, which somewhat resembles that of the hemolysin in paroxysmal hemoglobinuria, has led us to consider whether the blood destruction might not be due to accidental chilling of the animal. Efforts to induce a fall in the hemoglobin by placing the rabbit's ear in ice water have as yet been unsuccessful. Thus far no adequate search for an hemolysin has been made. The object of the present paper has been to describe a condition in which large amounts of free antigen and antibody circulate together in the organism, and to demonstrate the factor which prevents their union, the results of which could easily be fatal. The causes of the condition will be dealt with in a subsequent communication.

A study of acute mercuric chloride intoxications in the dog with special reference to the kidney injury.

Abstract: A study of the experiments comprising the first group of animals permits the deduction that these animals succumb to the acute poisoning as a result of the shock which the poison induces through its corrosive action in the stomach and intestine. The animals die before the mercury, acting as such during its elimination by the kidney, can induce an acute nephropathy and before the mercury, by inducing an acid intoxication, can lead to an acute kidney injury. The remaining animals of the series, Groups II, III, and IV, have withstood the corrosive action of the poison. These animals have shown the same type of delayed intoxication from the poison. The intoxication, however, has varied in time of appearance, duration, and severity. The animals classified as Group II have developed during the stage of improvement from the gastroenteritis a rapid and severe type of acid intoxication, have become rapidly anuric, and have died either in a state of air-hunger or in convulsions. The animals of Group III, either during or after their recovery from the gastroenteritis, have developed a mild grade of acid intoxication. During the following days of the experiments the animals succeeded in reestablishing their normal acid-base equilibrium. All the animals of this group recovered. The animals of Group IV have shown a recovery from the mercury enteritis. Following a period during which there was an attempt on the part of the animals to return to normal, as indicated by an increase in the alkali reserve of the blood and by an increased output of phenolsulfonephthalein and urine, the members of the group developed a delayed acid intoxication, and, like the animals of Group II, became anuric.

Spirochaeta hebdomadis, the causative agent of seven day fever (nanukayami) : first paper.

Abstract: A new species of spirochete which we have called Spirochaeta hebdomadis has been described as the specific etiological agent of seven day fever, a disease prevailing in the autumn in Fukuoka and other parts of Japan. This spirochete is distinguishable from Spirochaeta icterohaemorrhagiae to which it presents certain similarities. Young guinea pigs are susceptible to inoculation with the blood of patients and to pure cultures of the spirochete, and those developing infection exhibit definite symptoms suggestive of those of seven day fever in man. The blood serum of convalescents from seven day fever contains specific immune bodies acting spirochetolytically and spirocheticidally against the specific spirochetes, but not against Spirochaeta icterohaemorrhagiae. The field mouse (Microtus montebelli) is the normal host of the spirochetes, which have been detected in the kidneys and urine of 3.3 per cent of the animals examined. The endemic area of prevalence of seven day fever corresponds with the region in which field mice abound.

The solvent action of antiseptics on necrotic tissue.

Abstract: 1. Dakin's hypochlorite solution has the power of dissolving necrotic tissue, pus, and plasma clot in the concentration and reaction used clinically. 2. Chloramine-T and dichloramine-T do not exhibit this action. 3. The solvent action of Dakin's hypochlorite solution of the degree of alkalinity used clinically is due primarily to its hypochlorite content, but its slight alkalinity, while in itself without solvent action, enhances the effectiveness of the hypochlorite. 4. In the degree of alkalinity used clinically, the solvent action of hypochlorite is absent below about 0.2 per cent sodium hypochlorite concentration. 5. The hypochlorite concentration at which the solvent action ceases is lower the more alkaline the solution, and vice versa. 6. None of the antiseptics studied had demonstrable solvent action on blood clot.

Proteose intoxications and injury of body protein : iv. the metabolism of dogs with sterile abscess, pancreatitis, and pleuritis.

Abstract: Sterile abscess, pleuritis, and pancreatitis give a clinical reaction in the experimental animal very like the same acute inflammatory processes due to bacterial activity, provided the bacterial agents are limited to the initial location. The curve of urinary nitrogen excretion in the fasting dog shows the same precipitous and sustained rise in sterile and bacterial inflammatory reactions. This indicates that the same type of protein injury and autolysis in the body is produced by the sterile inflammatory reaction as by the bacterial reaction. It is assumed that the primary effect of the chemical agent or of the bacterial growth in the tissues is local cell injury or necrosis. This injured cell protoplasm undergoes prompt autolysis with escape of toxic protein split products. These toxic protein split products may be, in part at least, of the proteose group and are absorbed into the circulation, producing the familiar general reaction. The injury of body protein is obvious from the great increase in elimination of nitrogen in the urine and appears to be the same in sterile and in bacterial inflammation. The injurious agent in the sterile inflammation must be derived from the host protein, and we may assume with safety that much of the injurious material emanating from a septic inflammation must come from the host protein rather than from the bacteria. Acute sterile pancreatitis is one of the purest examples of an acute non-specific reaction where the intensity of the host's intoxication may reach a maximum in 12 to 24 hours. We believe that fundamentally this reaction is very similar to that observed after the production of a sterile abscess or pleurisy. Non-specific intoxication must account for the sterile reactions described above. Septic inflammations show the same acute reaction and injury of body protein. The deduction is obvious-that a great part, at least, of the reaction in septic inflammation is truly non-specific and results from the primary injury of the host's protein and cell autolysis.

Studies in bovine mastitis : i. non-hemolytic streptococci in inflammation of the udder.

Abstract: Aside from the streptococci, micrococci have been the next most frequent group of organisms isolated from inflamed udders They produce various types of disease Some give rise to only a mild catarrh of the larger milk ducts and cystern, while others produce more or less severe parenchymatous inflammation On the whole, the prognosis is more favorable with micrococcic infection than with that associated with streptococci Cases of considerable severity have, however, been attributed to staphylococci Micrococci similar in many respects to those associated with mastitis have been found to occur in the normal udder This has led Savage to question their true etiological significance In many instances micrococci may gain access to the udder and produce slight disturbances that are entirely overlooked Even more severe changes may follow infection After recovery the organisms still remain in the milk This was observed in the case of Cow 60 infected with staphylococci One frequently observes the elimination of streptococci from the udder even after apparent recovery from an attack of streptococcic mastitis Doubtless streptococci and micrococci observed in these udders would be classed as belonging to the normal flora Even though micrococci do occur in supposedly normal udders Evans has shown that many are pathogenic for rabbits The introduction of these organisms into the udders of non-resistant individuals might well give rise to more or less intense inflammation The multiplication would doubtless be rapid until resistance had been established In addition to the micrococci two other groups of rod-shaped organisms have been found associated with udder inflammation In two instances Bacillus coli has been isolated from cases of mastitis and in another Bacillus lactis aerogenes In four, tiny motile Gramstaining microorganisms have been obtained in pure culture Two of these strains (Nos C79 and M44) have been identified as Bacillus pyogenes

A pleomorphic bacillus from pneumonic lungs of calves simulating actinomyces

Abstract: A bacillus was found associated in pure culture with an extensive lobar bronchopneumonia in calves. It occurs in the exudate as a minute bacillus in small groups. In cultures it appears in three forms: as a bacillus, as a coccus-like endospore or arthrospore, and as a conglomerate Actinomyces-like flake or colony with peripheral clubs. The bacillar and coccoid forms occur on agar, the Actinomyces form in the condensation water of coagulated serum (horse). The coccoid form is probably a spore state, the minute refringent spore being contained in a roundish, unstainable mass representing either the remnants of bacillar substance or some capsular material. The somewhat striking similarities between this organism and Actinomyces are expressed by the massed growth with terminal clubs, the bacillar and coccoid stages, all of which are characteristic of Actinomyces. Sealing the tubes is essential for multiplication. Cultures must be renewed within a few days, otherwise multiplication fails. The substance which forms the bulk of the radiate flocculi is probably of capsular nature, greatly overproduced in serum tubes and scarce or absent on agar. Its nature is unknown. The organism is not appreciably pathogenic when injected into certain small laboratory animals.

Immunity in intestinal obstruction.

Abstract: 1. There is no increased immunity or tolerance to intestinal obstruction after recovery from previous obstruction. 2. Dogs recovered from intestinal obstruction are not more resistant to injections of closed loop fluid than normal dogs. 3. Dogs injected with closed loop fluid are not more resistant to intestinal obstruction than normal dogs. 4. In dogs the normal variation in resistance both to intestinal obstruction and to the injection of closed loop fluid is large.

Renal function in experimental hydronephrosis.

Abstract: Complete obstruction of the ureter causes atrophy of the renal parenchyma, especially marked in the portions lateral to the renal sinus. The longer the duration of the obstruction, the greater is the degree of atrophy. If the obstruction is removed within 2 weeks the kidney may regain its normal structure except for a varying amount of atrophy in the lateral portions. Kidneys obstructed for 2 weeks or less may regain their normal function, as measured by the phthalein test. The longer the period of obstruction, the slower is the rate of recovery. A hydronephrosis of 7 days' duration required 40 days, and one of 14 days' duration required 152 days to recover normal function.

Further study on the cultural conditions of leptospira (spirochaeta) icterohaemorrhagiae.

Abstract: 1. The presence of suitable animal or human serum is essential for the cultivation of Leptospira icterohaemorrhagiae. 2. The nutrient value of serum is considerably reduced by heating to 60 degrees C. for 30 minutes and is destroyed by boiling (100 degrees C). Filtration through a Berkefeld filter does not diminish the nutrient value of the serum. 3. The cultural value of different animal sera varies considerably. It is entirely absent from the sera of the rat and the pig. The sera of the rabbit, horse, and goat are better suited for the growth of the organism than those of the guinea pig, sheep, donkey, or calf. Human serum is suitable, but not ascitic fluid. 4. Fresh or heated emulsions of the liver, kidney, heart muscle, or testicle of the normal guinea pig or rabbit have no cultural value for the organism. The same may be said of both the white and yolk of the hen's egg. 5. A luxuriant growth takes place in a medium of Ringer's solution to which more than 10 per cent of normal rabbit serum is added. There is only moderate growth with 5 per cent of serum, and none when less than 2 per cent is present. The use of an undiluted serum offers no advantage over a diluted one, provided the latter contains at least 10 per cent of serum. In the case of certain animal sera dilution seems to make them more suitable for cultivation purposes, owing perhaps to its reduction of their inherent alkalinity. 6. The tonicity of the culture medium has but little influence upon the growth and morphology of the organism. A medium containing distilled water as diluent or one containing 8 per cent sodium chloride seems to give identical results. The viability of the organism was greatest in a medium in which Ringer's solution or isotonic salt solution was used as diluent. 7. The reaction of the medium is an important factor in the cultivation of the organism, which thrives most vigorously in a medium of which the reaction is slightly alkaline, not exceeding that of the serum. If the reaction is neutral, the growth is meager, and the culture is short lived. When the reaction of a medium becomes alkaline by the addition of a small amount of sodium hydroxide, or faintly acid by the addition of a little hydrochloric acid, no growth can take place. 8. Leptospira icterohaemorrhagiae is an obligatory aerobe. Any hindrance to the access of oxygen constitutes an unfavorable factor in obtaining a culture. 9. The addition of carbohydrates to media has no perceptible effect upon the growth or morphology of the organism. The reaction of the media is not modified by their presence. 10. Leptospira icterohaemorrhagiae grows at any temperature between 37 degrees and 10 degrees C., the optimum zone being 30-37 degrees C. Growth proceeds more rapidly at 37 degrees C. than at 30 degrees or at 25 degrees , but the cultures remain viable much longer at the latter temperatures. No growth takes place at 42 degrees C. 11. Three different media are described for the cultivation of freshly isolated strains. After prolonged cultivation on these media a strain may be readily cultivated in a serum diluted with Ringer's or isotonic salt solution.

Proteose intoxications and injury of body protein : iii. toxic protein catabolism and its influence upon the non-protein nitrogen partition of the blood.

Abstract: The acute intoxication following an injection of a toxic proteose is usually associated with a large increase (40 per cent or more) in the non-protein nitrogen of the blood. This increase is found chiefly in the blood urea nitrogen, but the amino and peptide nitrogens also may show small increases. The changes observed in the blood non-protein nitrogen are identical with those which follow the feeding of large amounts of meat (8). These facts indicate that the proteose intoxication causes an abnormally rapid autodigestion of tissue proteins, but that the nitrogenous end-products are, in chief part at least, the same that result from normal catabolism of food proteins. There is no evidence that the autolytic products play any part in causing the intoxication. The possibility of such a part and a resultant vicious circle is not excluded, but from the available facts the autolysis appears more as a result rather than cause of the intoxication. It appears possible that in disease or intoxication tissue catabolism may be enormously accelerated and yet yield the end-products of normal protein metabolism.

A report on antimeningitis vaccination and observations on agglutinins in the blood of chronic meningococcus carriers

Abstract: 1. A meningococcus vaccine suspended in salt solution has been given subcutaneously as a prophylactic to about 3,700 volunteers in three injections of 2,000 million, 4,000 million, and 4,000 or 8,000 million cocci at weekly intervals. 2. These doses rarely caused more than the mildest local and general reactions. Exceptionally a more severe reaction emphasized the presence of an unusual individual susceptibility to the vaccine. In such instances the symptoms were in part those of meningeal irritation and sometimes simulated the onset of meningitis. 3. Specific meningococcus agglutinins have been demonstrated in the blood serum of vaccinated men as compared with normal controls. 4. Moreover, agglutinins have been demonstrated in the blood serum of chronic carriers of the meningococcus. Evidence is thus brought forward that the relative immunity of chronic carriers to epidemic meningitis may be due to the presence of specific antibodies in the blood stream.

A study of mitochondria in experimental poliomyelitis.

Abstract: Typical mitochondria can be found in the spinal ganglion cells of monkeys with experimental poliomyelitis, even when typical Nissl substance has disappeared, and mitochondria-like structures are found in the remaining protoplasm in the latest stage of neurophagocytosis.