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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A nonsurgical rabbit model of enteric Shigella infection was developed for studying the pathogenesis and immunology of shigellosis and for evaluating Shigella vaccine candidates. In this model, rabbits are made susceptible to Shigella infection by a pre-inoculation conditioning procedure consisting of a 36-h nonfeeding period, with 250 mg of tetracycline administered in 250 ml of drinking water, 75 mg of cimetidine given intravenously, and two 15-ml doses of 5% sodium bicarbonate given orally immediately before orogastric administration of the bacterial inoculum. Lastly 2 ml of tincture of opium is administered intraperitoneally. With a virulent strain, Shigella flexneri 2a, the clinical and pathologic characteristics of shigellosis in this rabbit model were studied. Twenty hours after oral inoculation of 10(10) bacteria, all six experimental rabbits developed diarrhea and were lethargic or moribund, whereas the four control rabbits inoculated with sterile broth remained healthy. Histologic examination revealed severe, diffuse, necrotizing ileitis with hemorrhage in experimental rabbits, whereas no lesions were found in the controls. Although the major site of necrosis in this rabbit model was the ileum, as opposed to the colon in humans and nonhuman primates, the histologic morphology of the lesion was the same in the various hosts. Because it is relatively inexpensive and convenient, this model should facilitate study of the pathophysiology and immunology of shigellosis, thereby speeding development of oral vaccines, which can be tested in this animal model.
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PMID:Pathologic study of a rabbit model for shigellosis. 869 22

It is just a century since Abraham Flexner was invited by the Carnegie Foundation to evaluate medical education in the U.S. and Canada. After a visit to all of the existing medical schools at that time, Flexner issued a report in 1910 that revolutionized American and Canadian medical schools. The demise of proprietary schools, the solidification of ties between medical schools and universities and the introduction of the laboratory into the curriculum were outcomes that inaugurated the Flexnerian era in medical education. American and Canadian schools became the world's leaders. The educational patterns that emanated from the report dominated medical school curricula for the remainder of the 20(th) century. But as science and medicine changed drastically during the past 50 years, medical education has floundered and changed little. Although the environs of clinical education (hospitals and clinics) are dramatically different than 50 years ago, the process of clinical training has barely changed. That education is a science has yet to be fully acknowledged by medicine-witness the lack of continuity of undergraduate, post-graduate and continuing education. Medical education remains an 'orphan' supported by clinical practice and research in the same fashion that medical educators are 'orphans' in the academic promotions process. There is need for a modern day Abe Flexner-someone to pull the disparate parts together, to shake-up the lethargy and complacency, to streamline medical education into the 21(st) century.
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PMID:Abe Flexner, where are you? We need you! 1852 92

In the preceding experiments observations have been reported upon the nature of herpes virus which confirm the suspicion that the virus is intracellularly located in the infected nervous system. In regard to the immunological conditions existing in this disease, our experiments have reaffirmed that herpes virus can be neutralized with the serum of actively immunized animals and have offered an explanation for the irregularity of the results of others, as well as our own. It has been found that brain extracts possess some virus-neutralizing power, but considerably less than the serum of the corresponding animals. Attempts at passive immunization with neutralizing serum were uniformly negative, even when the serum was introduced into the cisterna magna 12 to 24 hours before infection with the virus. It has been shown that active immunity can be attained only when some degree of reaction to the living virus has occurred. Rabbits which survived neutralized serum-virus mixtures did not acquire immunity nor did those treated with virus phenolized to the extent of actual destruction. This point suggests a reinvestigation of the Semple method of rabies immunization. In so far as our studies touched upon the herpes-encephalitis problem we have uniformly failed in attempts to transfer herpes virus directly from man to rabbits. These results are in contradiction to those of most of the earlier workers, but in keeping with the recent reports of Flexner and Amoss. Attempts to overcome the difficulty of transfer by the recently published technique of Perdrau were unsuccessful. Furthermore, animals repeatedly treated with human encephalitis material, either fresh or glycerolated, as practised in the Perdrau method, failed to acquire the slightest degree of immunity to subsequent herpes inoculation. By the inoculation of very small doses or by infection of partially immunized rabbits, as described above, we have succeeded in modifying the characteristic herpetic syndrome in rabbits in a manner which simulates many of the clinical features of human encephalitis. Our own experience forces the conclusion that no valid proof exists upon which can be based an assertion concerning the identity of the virus of herpes with that of encephalitis lethargica. Either the two viruses are entirely unrelated, or else prolonged sojourn in the central nervous system of man attenuates the virus for rabbits to an extent analogous to that in which rabies virus is attenuated for man by passage through rabbits. The isolated successes of Levaditi and of Doerr and their assistants might thus be regarded as fortunate exceptions in which material incompletely attenuated had been at their disposal. We suggest this point of view as an alternative working hypothesis largely because the results we are reporting, as well as those of Flexner and Amoss, are in flat contradiction to the reported successes of earlier workers and the more recent experiments of Perdrau. The experiments of the latter, as described, cannot be explained by the occasional existence of spontaneous encephalitis in his rabbits, nor by the assumption that a herpes virus fortuitously coexisted with that of lethargic encephalitis in his material, inasmuch as this material alone at first injection or in the unglycerolated state failed to infect. It is also possible to conceive that human beings may, by repeated skin infections, attain a not inconsiderable partial immunity to herpes virus, which would explain the nature of the clinical course (as in our partial immunity rabbits) as well as the innocuousness of direct injections of herpetic virus into man, as reported by Bastai and Busacca, and the finding of herpes virus in human beings not suffering from lethargic encephalitis. These suggestions are discussed in order to give this important problem the broadest possible consideration. For the time being, however, such reasoning cannot be taken as more than a logical possibility impressed upon us by our partial immunization experiments. All other experimental evidence obtained by direct inoculations with the limited material at our disposal tends to render identity of the two varieties of viruses unlikely.
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PMID:IMMUNOLOGICAL STUDIES WITH HERPES VIRUS WITH A CONSIDERATION OF THE HERPES-ENCEPHALITIS PROBLEM. 1986 71