scholarly journals ETIOLOGY OF YELLOW FEVER

1919 ◽  
Vol 30 (2) ◽  
pp. 87-93 ◽  
Author(s):  
Hideyo Noguchi

Examinations of fresh blood from yellow fever patients by means of the dark-field microscope, made in more than twenty-seven cases, revealed in three cases the presence of Leptospira icteroides. In no instance was a large number of organisms found, a long search being required before one was encountered. The injection of the blood into guinea pigs from two of the three positive cases induced in the animals a fatal infection, while the blood from the third positive case failed to infect the guinea pigs fatally. Careful but by no means exhaustive dark-field searches for the leptospira with fresh specimens of blood from the remaining cases of yellow fever ended without positive findings, although four of the specimens, when injected into guinea pigs, caused a fatal leptospira infection. Stained blood film preparations from the corresponding cases were also examined, but the percentage showing the leptospira in the blood was no greater than that found by examination in the fresh state with the dark-field microscope. In fact, owing to the defective stains that were available at the time of the investigation a great many slides did not take the proper coloration with Giemsa's or Wright's stain and could not be relied upon. Regarding the presence of Leptospira icteroides in various organs both dark-field and stained films were examined. In only one instance so far a few organisms were detected in the emulsion of liver taken shortly after death from a case dying on the 4th day of yellow fever. This part of the work will be reported later upon completion. Examinations of the urine from different cases of yellow fever were made both by dark-field microscope and by inoculation into guinea pigs. The results were totally negative in thirteen cases, including many convalescents, but in one case one of the guinea pigs inoculated with 10 cc. of the urine came down on the 15th day with suggestive symptoms (suspicion of jaundice, and some hemorrhagic and parenchymatous lesions of the lungs and kidneys). This specimen showed no leptospira by dark-field examination. In experimental infection of guinea pigs with Leptospira icteroides the blood became infective in many instances 48 hours after inoculation, and was always infective after 72 hours. The liver and kidney become infective simultaneously with the blood. Detection of the organism by means of the dark-field microscope has seldom been accomplished before the 5th day. The organisms are most abundant on the 6th to the 7th day, but become fewer or completely disappear before death. In the meanwhile the number of organisms increases in the liver and kidney, from which they disappear as the jaundice and other symptoms become aggravated. When death occurs these organs seem to have lost most of the leptospira) and positive transfer by means of them is less certain. At the later stage of the disease the blood is often free from the organisms and ceases to be infective. Positive transmission with blood obtained from moribund animals is not impossible, however, even when no leptospira can be detected under the dark-field microscope.

1920 ◽  
Vol 32 (5) ◽  
pp. 601-625 ◽  
Author(s):  
Hideyo Noguchi ◽  
I. J. Kligler

Injections into guinea pigs of the blood and the emulsions of liver and kidney obtained at autopsy from a fatal case of yellow fever in Merida induced in some of these animals, after a period of several days incubation, a rise of temperature which lasted 1, 2, or more days. When killed for examination at this febrile stage the animals invariably showed hemorrhagic areas of various size, sometimes few and sometimes numerous, in the lungs, and also, though less constantly, in the gastrointestinal mucosa, together with general hyperemia of the liver and kidneys. In a guinea pig (No. 6) inoculated with the liver emulsion of Case 1 there was a trace of jaundice on the 9th day. Injections of the blood or liver and kidney emulsions from such animals into normal guinea pigs reproduced the febrile reactions and the visceral lesions. The majority of the animals which were allowed to live and complete the course of the infection rapidly returned to normal (within several days). Examinations of these surviving guinea pigs after 2 weeks revealed the presence of rather old hemorrhagic foci in the lungs. In the course of further attempts to transfer the passage strain, a secondary infection by a bacillus of the paratyphoid group caused many deaths among the guinea pigs and resulted finally in the loss of the strain from Case 1. Most of the cultures made with the heart's blood taken at autopsy from Case 1 proved to be contaminated with a bacillus of the coli group. The contents of the apparently uncontaminated tubes were inoculated into guinea pigs, but the results were for the most part negative or vitiated by a secondary infection. Dark-field search for the leptospira with the autopsy materials was negative, although prolonged and thorough examination was not practicable at the time of these experiments. Our efforts were concentrated on obtaining positive animal transmission rather than on the time-consuming demonstration of the leptospira, which when unsuccessful does not necessarily exclude the presence of the organism in small numbers. Likewise, the dark-field work with the material from guinea pigs was confined to a brief examination and was omitted in many instances. Under these circumstances no leptospira was encountered in any of the material from Case 1. On the other hand, the results obtained with the specimens of blood from Case 2 were definitely positive, not only in the transmission of the disease directly, or indirectly by means of cultures, into guinea pigs, but also in the demonstration of the leptospira in the primary cultures and in the blood and organ emulsions of guinea pigs experimentally infected with such cultures. Definite positive direct transmissions were obtained with the specimens of blood drawn on the 2nd and 3rd days. No blood was taken on the 4th or 6th days. There were indications of abortive or mild leptospira infection in the guinea pigs inoculated with the blood taken on the 5th day. Regarding the inoculation of cultures from Case 2, it may be stated that only the cultures (leptospira +) made with the blood drawn on the 2nd day caused a definite fatal infection in guinea pigs. From this series a continuous passage in the guinea pig has been successfully accomplished. One of the guinea pigs (No. 48) inoculated with the culture 5 days old (leptospira +) made from the blood taken on the 3rd day presented typical symptoms, and a positive transfer from this to another animal (No. 98) was also made. Cultures of the blood drawn on the 5th and 7th days gave unsatisfactory results, owing to a secondary contamination. Leptospiras were detected in some of the culture tubes containing 2nd and 3rd day specimens of blood from Case 2; they were few in number and for the most part immotile, owing perhaps to some unfavorable cultural condition such as a fungus contamination. Charts 17, 18, and 19 give a summary of the experiments. See PDF for Structure


1920 ◽  
Vol 31 (2) ◽  
pp. 159-168 ◽  
Author(s):  
Hideyo Noguchi

The use ot a polyvalent immune serum ot nign potency in tne treatment of an experimental infection of guinea pigs with Leptospira icteroides was found to be of definite advantage in checking the progress of the infection. When administered during the period of incubation the serum was found capable of completely preventing the development of the disease, although on subsequent examination hemorrhagic lesions of greater or less number and extent were found in the lungs of the guinea pigs which survived. Moreover, the serum modified the course of the disease and when used in the early stages of infection prevented a fatal outcome. Employed at a later stage, however, when jaundice and nephritis had been present for several days and the animal was near collapse, the serum had no perceptible beneficial effect. This was, of course, to be expected in view of the incidence of various pathological phases of this disease—nephritis, hepatitis, and other toxic symptoms in succession. In man the clinical manifestations are more gradual and distinct than in the guinea pig, yet the yellow fever patient whose temperature is sub-normal, and who has reached the stage of hemorrhages from the gums, nose, stomach, and intestines, and of uremia and cholemia, would seem to have little or no chance of deriving benefit from the use of a specific immune serum. This latter assumption would probably hold irrespective of the relation which Leptospira icteroides proves to have to the etiology of yellow fever.


1919 ◽  
Vol 29 (6) ◽  
pp. 585-596 ◽  
Author(s):  
Hideyo Noguchi

Studies are reported on the type of disease induced in guinea pigs, dogs, and monkeys by inoculating them (1) with the blood or organ emulsions of guinea pigs or other susceptible animals experimentally infected with Leptospira icteroides, and (2) with a pure culture of the organism. Particular attention has been given in these experiments to the clinical features of the experimental infection in the various animals and to the pathological changes resulting from the infection. The symptoms and pathological lesions induced in guinea pigs are much more pronounced than those observed in dogs or marmosets. The period of incubation is nearly the same in all three species, 72 to 96 hours with intraperitoneal or subcutaneous inoculation, and a day or more longer when the infection is induced percutaneously or per os. The febrile reaction in the guinea pig and marmoset is about the same; in the dog there is less fever. The amount of albumin, casts, and bile pigments in the urine is more abundant in the guinea pig and marmoset than in the dog, and these animals also appear on the whole to become more intensely icteric. The black or bilious vomit, however, though occurring frequently in dogs during life, is observed in the guinea pig and marmoset at autopsy. The hemorrhagic diathesis is most pronounced in guinea pigs, less so in marmosets, and least in dogs. In dogs) for example, subcutaneous hemorrhages almost never occur, and the lungs usually show only a few minute ecchymoses. The pleurse, pericardium, and other serous surfaces of the thorax and abdomen remain free from ecchymoses, which, however, with hyperemia, are very marked along the gastrointestinal tract. The symptoms and lesions observed in animals experimentally infected with Leptospira icteroides closely parallel those of human yellow fever. The pathological changes occurring in human cases of yellow fever are similar to those induced by inoculation in guinea pigs and marmosets and in respect to their intensity stand intermediate between those arising in the two animals mentioned.


1919 ◽  
Vol 30 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Hideyo Noguchi

The majority of guinea pigs inoculated with the blood of yellow fever patients escaped a fatal infection. There were a number of instances in which the inoculation of yellow fever blood induced in these animals a temporary febrile reaction on the 4th or 5th day, followed in some cases by slight jaundice, but with a rapid return to normal. Most of these guinea pigs when later inoculated with an organ emulsion of a passage strain of Leptospira icteroides resisted the infection. On the other hand, the animals which had previously been inoculated with the blood of malaria patients or normal guinea pigs died of the typical experimental infection after being inoculated with the infectious organ emulsion. It appears from the results just described that a number of nonfatal, mild, or abortive infections follow the inoculation of blood of yellow fever patients into guinea pigs. The fact that such animals manifested refractoriness to a subsequent attempt to infect with a highly virulent passage strain of Leptospira icteroides is an indication, judging from the reciprocal immunity reaction, that they actually passed through an infection with the same organism, or a strain closely related to it, as that which was used for the second infection experiment


1919 ◽  
Vol 30 (1) ◽  
pp. 9-12 ◽  
Author(s):  
Hideyo Noguchi

The serum from a number of persons recovering from yellow fever in Guayaquil was studied with a view to establishing its possible immunological relationship with a strain of Leptospira icteroides derived from one of the yellow fever patients. For this purpose the serum of convalescents was mixed either with an organ emulsion of a passage strain, or with a culture of the organism, and inoculated intraperitoneally into guinea pigs. The Pfeiffer reaction was first studied, and then the animals were allowed to live until the controls, inoculated with the same emulsion or culture of Leptospira icteroides but without the serum, or with serum from patients suffering from other diseases than yellow fever, had died of the experimental infection with typical symptoms A positive Pfeiffer phenomenon was observed in fifteen of the eighteen convalescent cases studied, or approximately 83 per cent. Sera from ten non-immune soldiers and from two malaria patients gave uniformly negative results. Protection from an ultimate fatal infection was afforded some of the guinea pigs which received the serum of yellow fever convalescents, while the control animals succumbed to the infection with typical symptoms. In one instance, in which the serum was tested on the 2nd and the 10th days of disease, a Pfeiffer reaction was demonstrated, as well as protective property against the infection, in the specimen from the 10th but not in that from the 2nd day. From the foregoing observations of immunity reactions it appears highly probable that Leptospira icteroides is etiologically related to yellow fever.


1921 ◽  
Vol 33 (6) ◽  
pp. 683-692 ◽  
Author(s):  
Alfred E. Cohn ◽  
Hideyo Noguchi

1. Slowing of the heart occurred in monkeys and guinea pigs during the febrile period of the experimental infection due to Leptospira icteroides. A similar reaction took place in animals inoculated with Leptospira icterohœmorrhagiœ. 2. The mechanism of slowing was usually due to slowing of the whole heart. 3. Once incomplete heart block was seen. Changes in the ventricular complex occurred four times.


1921 ◽  
Vol 33 (2) ◽  
pp. 239-252 ◽  
Author(s):  
Hideyo Noguchi ◽  
I. J. Kligler

Fourteen typical cases of yellow fever were studied in northern Peru during an epidemic occurring in 1920, nine in Payta in March and April, and five in Morropon and Piura in April and May. The method of investigation was similar to that previously employed, but as the laboratory facilities were very meager certain changes were required. Although in Payta the work was handicapped by the lack of electric light, the scarcity of water and animal food, the unsuitability of the guinea pigs for inoculation, and the changes in culture media due to age, the results obtained under these adverse conditions were by no means negative. While in no instance was there a typical infection produced in animals, either by direct inoculation of blood or with culture materials, yet certain guinea pigs in each series showed temporary febrile reactions or definite hemorrhagic lesions of the lungs indicative of a mild leptospira infection. Direct search for Leptospira icteroides in the blood of patients or in culture materials was not made because the dark-field microscope could not be used. Subsequently, at Piura, the laboratory facilities were vastly, improved, the use of the dark-field microscope was made possible by means of a storage battery, and a fresh stock of young healthy guinea pigs was received from New York, and fresh rabbit serum obtained in Piura. In the study of the materials obtained from five cases of yellow fever in Morropon all these added facilities were taken advantage of, with the result that the outcome was positive and convincing. Cultures from the five cases were examined after 11, 12, and 13 days, and in those from three cases living leptospiras were found. By inoculation into suitable guinea pigs of culture material from these five cases, irrespective of whether or not leptospiras were detected under the dark-field microscope, a typical Leptospira icteroides infection was produced from four of the five cases. In one of these no leptospira had been detected in the culture tubes. Thus one case only yielded negative results, in that no leptospiras were found under the dark-field microscope and the animal inoculation was negative. The leptospira was demonstrated in the blood or organ emulsions of the infected guinea pigs, and further transmission of each strain to other guinea pigs was obtained and pure cultures were secured. A few points of practical significance appeared in the course of the present investigation. One is the importance of using fresh rabbit serum for culture media. Old rabbit serum, whether in pure form or incorporated with agar, etc., which had been kept for several months in a tropical climate, proved to be unsatisfactory for obtaining a growth of Leptospira icteroides. A second point of interest is the variation in susceptibility of guinea pigs to infection with Leptospira icteroides. In two of four series of positive animal inoculations with the Morropon culture materials only one-half of the guinea pigs inoculated with given materials developed typical symptoms. The other half either suffered from a transient mild infection, as evidenced by a few hemorrhagic foci in the lungs, or escaped infection altogether. From these facts it is highly probable that the lung lesions and febrile reactions observed in certain guinea pigs inoculated with the Payta materials were due to a mild leptospira infection. In a comparative experiment the native guinea pigs procured in Payta were found to be more resistant to the leptospira infection than those recently brought from New York. In fact, only a small portion of the former succumbed to typical infection even when inoculated with a virulent strain of Leptospira icteroides obtained from the Morropon epidemic. In conclusion it may be stated that of fourteen cases of yellow fever studied in Peru, a typical leptospira infection, together with the demonstration of the organism in experimentally infected guinea pigs, was obtained in four, while in the majority of instances indications of a mild, non-fatal leptospira infection were observed. In a few cases only were the results entirely negative. The leptospira isolated from Morropon cases of yellow fever, which is morphologically and culturally identical with the Guayaquil and Merida strains of Leptospira icteroides, was also shown by immunity test to be indistinguishable from the Guayaquil organism.


Author(s):  
В. Зинько ◽  
V. Zin'ko ◽  
А. Зверев ◽  
A. Zverev ◽  
М. Федин ◽  
...  

The seismoacoustical investigations was made in the western part of the Kerch strait (Azov sea) near Kamysh-Burun spit. The fracture zone with dislocated sedimentary rocks layers and buried erosional surface was revealed to the west of spit. Three seismofacial units was revealed to the east of spit. The first unit was modern sedimentary cover. The second ones has cross-bedding features and was, probably, the part of early generation of Kamysh-Burun spit, which lied to the east of its modern position. The lower border of the second unit is the erosional surface supposed of phanagorian age. The third unit is screened by acoustic shedows in large part.


Author(s):  
Nora Goldschmidt ◽  
Barbara Graziosi

The Introduction sheds light on the reception of classical poetry by focusing on the materiality of the poets’ bodies and their tombs. It outlines four sets of issues, or commonplaces, that govern the organization of the entire volume. The first concerns the opposition between literature and material culture, the life of the mind vs the apprehensions of the body—which fails to acknowledge that poetry emerges from and is attended to by the mortal body. The second concerns the religious significance of the tomb and its location in a mythical landscape which is shaped, in part, by poetry. The third investigates the literary graveyard as a place where poets’ bodies and poetic corpora are collected. Finally, the alleged ‘tomb of Virgil’ provides a specific site where the major claims made in this volume can be most easily be tested.


1944 ◽  
Vol 151 (1) ◽  
pp. 70-86
Author(s):  
W. Littlejohn Philip

The paper is limited to the application of hydraulic power to lathes designed for shell making although, in the author's opinion, there is an immense field for the application of the same principles in other directions. Self-contained hydraulic machine tools have been dealt with by Mr. H. C. Town,† but in the system to be described all the machines are operated from a central hydraulic plant. Three complete installations on this principle have been established by the author, and the present paper contains an account of this work from the first experiments in 1915 until about four years ago. The first plant was constructed in 1915 for the production of 3·29-inch shells, known as “18-pounders”, from the solid bar. The output was 2,000 shells per week of 135 hours, with girl operators working on three shifts. The second plant was put down in 1916–17 for an output of 500 9·2-inch howitzer shells per week of 135 hours, also with girls working on three shifts. The third plant is of recent design. It was started in 1938 for the production of 3·45-inch shells, known as “25-pounders”; and was laid out for an output of 1,000 shells per week of 47 hours. This plant included four types of hydraulic lathes which the author was engaged to design for the War Office. Soon after the commencement of the last war in 1914 it became evident that shell production would have to be greatly increased, and engineering firms were pressed to take up shell manufacture. The author, on behalf of his firm, undertook to help in the movement, and he at once set about the construction of some simple machines for the job. These conformed on general lines to the practice of the period as regards design and operation. He soon realized, however, that drastic changes would have to be made if production was to reach the high level that circumstances demanded. Although quite familiar with hydraulic machinery of various types and of many applications in presses and certain types of heavy tools, he was not aware of any instance in which hydraulic power had been applied to the movements of a lathe. It appeared to him, nevertheless, that it would be possible to construct a very useful machine on these lines, and he accordingly started immediately to carry out experiments and to prepare designs. It was considered essential that machines for the duty which the author had in mind should be much heavier and more rigid than the ordinary machines of the time, so that they should be free from vibration and “chatter” or spring with the heaviest possible cutting. The standard of rigidity aimed at was that which would permit a half-crown coin to remain balanced on edge on the moving saddle or turret while the tools were making the heaviest cuts. This object was achieved, and the demonstration was frequently made in the presence of those who came to see the lathes at work.


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