The Phenomenon of Local Tissue Reactivity to Bacterial Filtrates

Shwartzman, Gregory

doi:10.1001/jama.1936.02770500012004

Cited by 34 publications

(21 citation statements)

References 14 publications

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“…In some experiments a purified polysaccharide toxin derived from Serratia marcescens was employed; this material was supplied by Dr. Murray Shear. The methods used for the preparation of these materials are described in publications of these authors (4,5).…”

Section: Methodsmentioning

confidence: 99%

“…Several materials which produced visible local inflammatory reactions in the skin but did not bring about a state of reactivity to the Shwartzman phenomenon were studied. These included fresh undiluted human and horse serum, 1 per cent egg albumin, sterile broth, filtered broth cultures of group C hemolytic streptococci, and concentrated "agar washings" of cultures of the latter organism which were prepared in the same manner as meningococcal toxin (4). The materials were injected intradermally in 0.5 cc.…”

Section: Aerobic Glycolysis Of Normal and Prepared Skin--mentioning

confidence: 99%

“…It has been repeatedly demonstrated that hemorrhagic necrosis can be produced in such tumors by intravenous injection of those bacterial toxins capable of eliciting the Shwartzman phenomenon (4,5). The mechanism by which hemorrhage is brought about in tumors has never been explained.…”

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confidence: 99%

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Studies on the Mechanism of the Shwartzman Phenomenon

Thomas

Stetson

1949

Journal of Experimental Medicine

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Rabbit skin which is prepared for the Shwartzman phenomenon by an intradermal injection of meningococcal toxin exhibits, in vitro, a high degree of aerobic glycolysis. This metabolic abnormality is reflected, in vivo, by a measurable increase in the concentration of lactic acid in the prepared skin. Some increase in anaerobic glycolysis also occurs in prepared skin; this is of less degree than the increase in aerobic glycolysis. The respiratory quotient of prepared skin tends to be somewhat higher than that of normal skin, although the oxygen uptake is not significantly altered. Gross hemorrhagic lesions which resemble the Shwartzman phenomenon are produced by the intradermal injection of papain into rabbits which have received an intravenous injection of meningococcal toxin 1 hour previously. Such hemorrhagic reactions are not observed when papain is injected into normal rabbit skin. Similarly, hemorrhagic lesions are produced by the intradermal injection of cysteine and BAL, following an intravenous injection of meningococcal toxin. An hypothesis to explain the Shwartzman phenomenon, which implicates tissue protease in the damage to the blood vessels of the skin, is proposed.

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Section: Methodsmentioning

confidence: 99%

Section: Aerobic Glycolysis Of Normal and Prepared Skin--mentioning

confidence: 99%

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Studies on the Mechanism of the Shwartzman Phenomenon

Thomas

Stetson

1949

Journal of Experimental Medicine

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“…These include suspensions of crude tissue extracts (14), rabbit liver glycogen (15,16), kaolin (16), starch (17), agar (18), fresh human serum (19), and antigen-antibody precipitates (20). It has also been shown that protein antigens will provoke the reaction in previously sensitized rabbits (20).…”

Section: Attempts To Imitate the Effect Of Tkorotrast And Trypan Bluementioning

confidence: 99%

Studies on the Generalized Shwartzman Reaction

Good

Thomas

1952

Journal of Experimental Medicine

145

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In an earlier communication (1), it was shown that treatment with cortisone caused a marked alteration in the response of rabbits to an injection of endotoxin from certain Gram-negative microorganishas. In normal animals, an intradermal injection of meningococcal or Serratia marcescens toxin resulted in a vigorous local inflammatory reaction, with visible erythema and edema of the involved skin. In cortisone-treated rabbits, there was little evidence of local inflammation; instead, numerous small hemorrhages appeared throughout the injected skin area. Histologically, these skin lesions showed occlusion of the small vessels by masses of leukocytes and platelets, an event shown by Stetson (2) to be characteristic of the developing Shwartzman reaction. Similarly, a single intravenous injection of toxin, which caused no tissue lesions in normal rabbits, was found to produce bilateral cortical necrosis of the kidneys in cortisone-treated animals. The renal lesion was identical with that of the generalized Shwartzman reaction, which is produced by giving two intravenous injections of toxin spaced 12 to 24 hours apart.These observations indicated that cortisone had an effect which was equivalent to one phase of the Shwartzman reaction. In attempting to account for the effect, the possibility was considered that a mechanism responsible for the removal, detoxification, or fixation of toxin might be interfered with by cortisone. Indirect evidence for such interference was obtained in the following manner. In normal rabbits very large amounts of meningococcal toxin can be injected intradermally without causing systemic intoxication and without pro-*

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“…The creation of damaged and relatively ischemic tissue tends to promote the growth of many types of pathogens, especially anaerobes, and among the commonly contaminating organisms are included several species capable of producing powerful exotoxins (89,90). The ready accessibility of clostridia, the fact that conditions for their growth and toxin production are optimal, and the potency of their characteristic toxins make it important to investigate the role which such bacteria might play in the sequence of changes that constitute the syndrome of traumatic shock.…”

Section: Discussionmentioning

confidence: 99%

The Toxic Factors in Exerimental Traumatic Shock. Vi. The Toxic Influence of the Bacterial Flora, Particularly Clostridium Welchii, in Exudates of Ischemic Muscle 1

Pope¹,

Zamecnik²,

Aub³

et al. 1945

J. Clin. Invest.

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As has been shown in previous reports from this laboratory (10, 25, 75), toxic effects resembling traumatic shock have been observed following the intravenous injection of fluids exuding from-dog muscles after prolonged ischemia.The fact that 28 per cent of these fluids were highly toxic, whereas the remainder seemed harmless, strongly suggested that their toxic effects were not due to the presence of intracellular substances lost as the result of cell damage (70). For the same reason, it appeared doubtful that the occasional toxic effects were caused by breakdown products of muscle cell constituents resulting from ischemia, since the experimental conditions were all approximately identical. Attention has been directed, therefore, to the one constituent of these fluids which was obviously highly variable, namely, the bacterial flora.Another bit of indirect evidence pointed in this direction. On several occasions, dog muscle tissue was excised and minced with sterile precautions and incubated in sterile dog plasma at 370 C., for 5 hours. The plasma was then separated by centrifugation and injected intravenously into recipient dogs. Such material was invariably toxic, rapidly producing a shock-like state and death, and it was always infected with micro-organisms which on direct smear were seen to be large gram-positive rods. However, if a mixture of blended dog muscle and plasma were sterilized by passage through a Seitz filter before incubation, of the fluid to be tested were mixed with 4.5 ml. of beef broth, and 3 successive 1: 10 dilutions in broth were made. Two blood agar plates were then divided into quadrants and a loopful (approximately 1I4.) of each dilution was streaked onto 1 quadrant of each plate. One of these was incubated aerobically and the other in an atmosphere of 5 per cent CO2 in nitrogen. After 36 hours of incubation at 37°C., differential colony counts were made and identification of the bacterial species present was undertaken. Colony counts were multiplied by the appropriate factors to give numbers of viable bacteria per ml. of original fluid, and these were checked qualitatively with observations on direct smears. Clostridia were isolated and cultivated from various fluids.In an attempt to reproduce at will the picture of toxicity following fluid injection, 2 strains of Clostridia perfringens thus isolated were used in 3 experiments. In these experiments, at the time of muscle ligation, 2 to 5 ml. of a broth culture of these organisms were injected into each of the 2 muscle groups; after the period of occlusion of the blood supply the ligatures were released as usual and fluid collected. These have been termed "reinforced" fluids. Bacterial counts were made on the first fluid obtained from each leg, on a final sample drain-856

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The Phenomenon of Local Tissue Reactivity to Bacterial Filtrates

Cited by 34 publications

References 14 publications

Studies on the Mechanism of the Shwartzman Phenomenon

Studies on the Mechanism of the Shwartzman Phenomenon

Studies on the Generalized Shwartzman Reaction

The Toxic Factors in Exerimental Traumatic Shock. Vi. The Toxic Influence of the Bacterial Flora, Particularly Clostridium Welchii, in Exudates of Ischemic Muscle 1

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