bluuebunny/crossref_metadata_2025_split huggingface dataset:
ETIOLOGY OF YELLOW FEVER
Authors: Noguchi Hideyo 
Published: June 2004

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.
AN EXPERIMENTAL STUDY OF FAT STARVATION WITH ESPECIAL REFERENCE TO THE PRODUCTION OF SEROUS ATROPHY OF FAT
Authors: Herter C. A. 
Published: June 2004

The following inferences may be made from the foregoing study:
1. The lesions resulting from fat starvation, at least in the case of pigs, do not resemble or even suggest those of rickets.
2. Prolonged fat starvation leads to the entire disappearance of fat from the adipose tissues. The form of fat atrophy observed as the result of experimental fat starvation corresponds to the serous fat atrophy described by Flemming, and is essentially the same type of fat atrophy as that found in the epicardial and perirenal fat in the human subject as the result of wasting disease.
3. The. lecithins of the brain and the fat of the liver are not materially reduced by fat starvation.
4. Fat starvation does not lead to advanced serous fat atrophy of the subcutaneous fat if the animal be given a large excess of carbohydrate food or a considerable excess of the carbohydrate and proteid constituents of milk.
5. Fat starvation causes a very imperfect absorption of the salts of P2O5 from the intestine.
THE FATE OF THE GIANT CELLS WHICH FORM IN THE ABSORPTION OF COAGULATED BLOOD SERUM IN THE ANTERIOR CHAMBER OF THE RABBIT'S EYE
Authors: Hektoen Ludvig 
Published: June 2004

The conclusion seems warranted that the giant cells formed in the absorption of coagulated blood serum inserted into the anterior chamber of the rabbit's eye subdivide again into uninuclear small cells that take part with other new-formed cells derived from the lining of this space to form a densely fibrillated mass of tissue that resembles quite closely the cornea in its structure.
This demonstration materially strengthens the opinion expressed by the writer in his previous article in this Journal,* that the giant cells in healing non-degenerated tuberculous tissue may separate into small living cells, and that the giant cells of tuberculosis are not necrobiotic elements from the very moment and from the very mode of their formation, as has been the general teaching, especially in Germany.
ETIOLOGY OF YELLOW FEVER
Authors: Noguchi Hideyo 
Published: June 2004

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
ETIOLOGY OF YELLOW FEVER
Authors: Noguchi Hideyo 
Published: June 2004

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.
STUDIES ON CYANOSIS
Authors: Lundsgaard Christen 
Published: June 2004

1. The primary cause of cyanosis is an increase in the reduced hemoglobin, or oxygen unsaturation, of the blood in the peripheral capillaries.
2. When the mean capillary oxygen unsaturation, which is calculated as the mean between venous and arterial unsaturation, and is normally about 2 to 3 volumes per cent, is increased to about 6 to 7 volumes per cent, cyanosis appears. For this reason 6 to 7 volumes per cent may be called the threshold value of mean capillary oxygen unsaturation for the incidence of cyanosis.
3. The increased mean capillary oxygen unsaturation is produced in two ways (secondary causes of cyanosis), either by an abnormally great reduction during passage through the capillaries (Text-fig. I, Diagram II) or by a state of partial reduction in the arterial blood entering the capillaries (Text-fig. I, Diagram III). The first condition (abnormally great reduction) occurs during exercise, or when the blood flow is retarded, as in decompensated heart condition. The second condition (partial arterial unsaturation) occurs in certain lung and heart diseases, and when the alveolar oxygen tension is greatly decreased, as at high altitudes.
4. If the blood is completely saturated with oxygen in the lungs, the oxygen unsaturation of the venous blood may increase to 13 to 14 volumes per cent before cyanosis appears.
5. If cyanosis appears at a venous oxygen unsaturation less than 13 to 14 volumes per cent, some arterial oxygen unsaturation may be assumed, and the more the lower the venous oxygen unsaturation is.
6. Even if neither râles nor dullness can be detected in the lungs, conditions may exist which prevent complete oxidation of the arterial hemoglobin. This is especially frequent in patients with mitral lesions.
7. Cyanosis cannot be produced in patients whose hemoglobin percentage is below 35 per cent on the Haldane scale (oxygen capacity of 6.5 volumes per cent).
THE BACTERIOLOGY OF BOVINE ABORTION, WITH SPECIAL REFERENCE TO ACQUIRED IMMUNITY
Authors: Smith Theobald 
Published: June 2004

In a large herd of dairy cattle and young stock the bacteriological examination of 109 cases of abortion which included a relatively thorough study of the fetus and a study of the membranes, or swabs from the uterus whenever obtainable, gave the following results. 62, or 57 per cent, were associated with Bacillus abortus. 26, or 23.8 per cent, were associated with spirilla. 2, or 1.8 per cent, were associated with Bacillus pyogenes. 19, or 17.4 per cent, were either sterile or else the digestive and respiratory tracts had been invaded during or after birth with miscellaneous bacteria. Bacillus abortus was absent according to cultures and animal tests.
Such a relatively large proportion of cases of abortion without Bacillus abortus as the inciting agent is noteworthy. In general Bacillus abortus was associated with first pregnancies. Its presence diminished rapidly in frequency in later pregnancies. Assuming in a general way that purchased cows coming from small herds were free from any immunity and that their first pregnancy in the new herd is equivalent to that of a native heifer and may be counted as the first, we have Bacillus abortus associated with the first pregnancy in 42, with the second in 14, with the third in 5, and with the fourth in 1. Spirilla were distributed as follows: (a) in purchased cows, first pregnancy, 6; second pregnancy, 9; third pregnancy, 5; and fourth pregnancy, 3; (b) in native cows, first pregnancy, 0; third pregnancy, 1; sixth pregnancy, 1; and eighth pregnancy) 1. The relation of infection with spirilla to acquired immunity is not clear and more data from large herds are needed to define both etiological and immunological bearings of the spirilla.
Thus far spirilla have not been encountered in native heifers of the herd giving birth the first time. A tentative explanation to be offered is that the young stock is kept segregated from the older and purchased cows until shortly before calving. The occasional discharge of a fetus among the young stock in pasture tends to keep up the disease due to Bacillus abortus. Later on association with older cows brings about infection with spirilla (Vibrio fetus) and more rarely with other possible agencies of fetal disease. On the other hand, abortions may occur among the pastured stock from time to time and remain unrecognized. Not until both groups of animals are subjected to the same daily scrutiny will it be possible to affirm that abortion associated with spirilla does or does not occur among young stock.
AN INTERPRETATION OF THE AGGLUTINATION REACTION TO BACILLUS ABORTUS IN 75 CASES OF BOVINE ABORTION BACTERIOLOGICALLY CONTROLLED
Authors: Smillie Ernest W. , Little Ralph B. , Florence Laura 
Published: June 2004

The agglutination test when carried out so as to give the entire range of serum dilutions to the limit of clumping is a delicate test which reflects a variety of conditions involved in infection with Bacillus abortus. Among these conditions are its time relation to the act of abortion and the length of time the abortion bacilli live and multiply in the pregnant uterus. It is obvious that if a uterus be infected in the 8th month of pregnancy, the opportunity for agglutinins to accumulate are poorer than if the uterine infection lasts 3 or 4 months. The presence of Bacillus abortus in the udder determines in many cases the intensity of the reaction. No definite rules can therefore be formulated for the interpretation of the agglutination reaction quantitatively, since it is bound up with a complicated process varying from case to case. In the individual cow in general a titer of 1:40 or less may be regarded as indicating that the cow is not infected with Bacillus abortus at the time of the blood examination. It does not exclude former infections in the case of older cows, nor does it absolutely exclude very recent infection (Nos. 278 and 351).
The highest titers, 1:640 and above, generally indicate recent infection and in the absence of recent premature births infection of the udder. Even when abortion has just occurred, it may be due to other agencies and the high titer maintained by a chronic infection of the udder dating from an earlier uterine infection with Bacillus abortus. Intermediate titers may indicate a gradual rise or decline of agglutinins preceding or following abortion without infection of the udder. They may also stand for a relatively high resistance or partial immunity of the cow.
In any herd a uniformly low titer (1:40 or less) in all animals may be regarded as indicating the entire absence of Bacillus abortus. A high titer in any one cow serves to indicate quite definitely the presence of infection in the herd. To determine more accurately the character of the infection in any individual cow there is needed in addition to the quantitative agglutination test a bacteriological study of the milk and of any prematurely discharged calf or fetus.
CHEMOTHERAPY OF TRYPANOSOME AND SPIROCHETE INFECTIONS
Authors: Pearce Louise , Brown Wade H. 
Published: June 2004

N-PhenyIglycineamide-p-arsonic acid is an agent of marked therapeutic action in the treatment of experimental trypanosomiasis of mice, rats, and guinea pigs. It possesses an average curative range of from 0.2 to 0.3 gm. per kilo of body weight of the sodium salt against a 24 hour infection in mice and rats produced by several species of pathogenic trypanosomes. Since the lethal dose for mice is from 2 to 2.25 gm. and for rats 0.75 gm. per kilo of body weight, we have curative ratios of 1:8 and 1:3 respectively. The curative dose for guinea pigs is 0.15 gm. per kilo of body weight, thus giving a curative ratio of 1:10. The trypanocidal activity of this compound is relatively rapid in all three animal species, for the peripheral blood is cleared of organisms within 24 hours after its administration, and in addition, the lower limits of the curative range are comparatively sharply defined. Intraperitoneal, intravenous, and subcutaneous routes of administration for all practical purposes may be considered equally efficacious in Tr. brucei infections of mice both as regards the speed of action of the drug and the average curative range. The administration of the drug in therapeutic amounts in all three animal species is not followed by manifestations of organic or functional injury, but, on the contrary, the genera] physical condition of the treated animals shows an immediate and continued marked improvement.
The therapeutic activity in trypanosomiasis of mice, rats, and guinea pigs as evidenced by the relative speed and sharpness of action, together with the curative ratio as expressed in fractions of the minimum lethal dose, and the absence of organic injury or functional disturbance following therapeutic doses are significant and characteristic features of the amide of N-phenylglycine-p-arsonic acid.
CHEMOTHERAPY OF TRYPANOSOME AND SPIROCHETE INFECTIONS
Authors: Brown Wade H. , Pearce Louise 
Published: June 2004

To summarize the results obtained from these experiments, one may say that N-phenylglycineamide-p-arsonic acid is capable of exercising a very definite effect upon the course of infections produced by spirochetes of the recurrens group and by Treponema pallidum. It is more difficult to say, however, just how these effects should be interpreted. In the case of the blood spirochetes, the infection is ameliorated, and even though the spirochetes are not immediately destroyed, the infection is frequently brought to a termination which leaves the animal in a condition not unlike that produced by more powerful spirocheticidal agents. That is, the infecting organisms are either affected in such a way that they eventually die off or are destroyed by the host in such a way that no lasting immunity is developed in consequence of their destruction.
Apparently much the same type of reaction occurs in the treatment of rabbits infected with Treponema pallidum. It is possible that when very large doses of the drug are used, these organisms may be completely destroyed, but it is certain that in other cases, where complete healing of the lesions is accomplished as a result of treatment, the organisms are not destroyed. Moreover, it appears that such a result can be accomplished in the presence of numerous actively motile spirochetes, and once the effect of the drug has reached this point, either the capacity of the spirochetes for stimulating reaction on the part of the tissues is lowered or else the reactivity of the tissues is reduced. At any rate., living spirochetes may remain in the tissues for considerable periods of time without giving rise to the usual tissue reaction which characterizes these infections.
With either group of organisms, therefore, N-phenylglycineamide-p-arsonic acid appears to act in a manner somewhat different from that of the usual spirocheticidal agents. While it does possess a considerable degree of spirocheticidal action, its chief effect is seen in the peculiar manner in which it modifies or controls the course of these infections.
Further than this, we shall not attempt to go at present. As set forth in the literature, the facts and principles upon which such experiments depend are so few as to offer almost no basis for an interpretation of these experiments. When we have had an opportunity of reporting our own experience in dealing with these infections, we may return to a consideration of the facts here reported.
THE PATHOLOGICAL CHANGES IN THE TESTES IN EPIDEMIC PNEUMONIA
Authors: Mills Ralph G. 
Published: June 2004

The testicular changes in pneumonia are without clinical manifestations, are non-specific, focal in character, independent of the infecting organisms or the antecedent disease, and vary in severity directly with the total length of the illness. The process is a continuous one, divisible into stages in which the following features are recognizable: (1) cessation of spermatogenesis; (2) degeneration of preformed spermatocytes, spermatids, and spermatozoa; (3) desquamation of altered cells and fragments of the same; (4) formation of giant cells in the tubule walls with subsequent liberation into the lumen; (5) disappearance of all desquamated cells and all those derived from the spermatogonia by mitosis; (6) in some instances thickening of the hyaline layer of the basement membrane.
Older lesions are frequently found which continue the structural alteration of the tubules by hyalinosis and destruction of cells until they ultimately disappear. These lesions are not believed to be connected with the present illness.
Edema may represent the acute injury in another form, and round cell infiltration suggests that possibly other factors than toxins may have a part in the tissue alterations.
In the absence of definite evidence to the contrary, the cause is assumed to be circulating toxins, as Wolbach (12) claims for influenzal cases.
The hemolytic streptococcus produced more extensive changes, both epithelial and interstitial, in primary pneumonia occurring during the measles epidemic than when pneumonia followed as a secondary infection; in the latter cases the pulmonary complications covered a relatively shorter period. Measles and epidemic influenza had little apparent effect upon the testes, except that the former caused mild inhibition of spermatogenesis; evidence regarding the latter is inconclusive.
The Pfeiffer bacillus was always associated with other organisms, in primary infections and in those following measles. It occurred alone in a few cases after epidemic influenza, but the testicular lesion was not distinctive.
The pneumococcus when alone in primary infections or after an epidemic disease produced a uniformly mild picture which was not intensified when associated with the influenza bacillus.
Giant cells were much more frequent after influenzal pneumonia regardless of its cause and were associated with large numbers of other desquamated cells. They are formed in the walls of tubules by futile mitotic effort and incomplete protoplasmic separation, the abnormality of the process being further suggested by the early severing of cytoplasmic attachments and rapid desquamation.
The series is unique in its uniformity, in the care exercised in the bacteriological examinations, and in the relative freedom from complicating factors.
A STRAIN OF CONNECTIVE TISSUE SEVEN YEARS OLD
Authors: Ebeling Albert H. 
Published: June 2004

1. A strain of connective tissue is still very active after more than 7 years of life in vitro.
2. The rate of growth of the fragments of tissue can be measured accurately and used for testing the action of many different factors on the growth of connective tissue cells.
3. The rate of growth of the strain is at least as rapid as it was 5 years ago, and may be more active.
4. The connective tissue cells appear to have the power of multiplying indefinitely in a culture medium, as do microorganisms.