scholarly journals EXPERIMENTAL PRODUCTION OF HEMORRHAGE AND VASCULAR LESIONS IN LYMPH NODES: AN EXTENSION OF THE SHWARTZMAN PHENOMENON

1937 ◽  
Vol 65 (2) ◽  
pp. 287-302 ◽  
Author(s):  
Lewis Henry Koplik
Keyword(s):  
Lymph Nodes ◽  
Intravenous Injection ◽  
Lymphatic Drainage ◽  
Intradermal Injection ◽  
Vascular Lesions ◽  
Experimental Production ◽  
Intravenous Injections ◽  
Shwartzman Reaction ◽  
High Concentrations ◽  
Shwartzman Phenomenon

Characteristic changes are produced in the lymph nodes of rabbits following the intravenous injection of certain bacterial filtrates administered 24 hours after either an intralymphatic or an intradermal injection of the same filtrate. These changes are limited to the nodes served by the lymphatic injected or to those furnishing the lymphatic drainage for the injected skin site. By either method the initial or preparatory injection of filtrate reaches the lymph nodes through one or more of its afferent lymphatics, and similar lesions are produced in the nodes. The lesions consist of hemorrhages recognizable by gross and microscopic examination. The capillaries and veins are congested and thrombosed. Their endothelial cells are swollen. Arterioles are generally little affected. Though hemorrhages and thromboses are usually seen together in the nodes, they have been observed occurring independently. They are both probably secondary to endothelial changes. The lesions are not dependent on the amount of preexisting inflammation in the nodes. Endothelial changes, hemorrhages and thromboses were usually noted in the regional nodes when positive Shwartzman reactions had been elicited in prepared skin by intravenous injection of the bacterial filtrate. However, these lesions in many instances were observed under similar conditions in these nodes even when the Shwartzman reaction in the skin was negative. It appears that lymph nodes are more susceptible to the production of the Shwartzman phenomenon than the skin sites which they drain. A single intralymphatic or intradermal injection of the bacterial filtrates used in this study, even in high concentrations, does not produce in adjacent lymph nodes the characteristic changes noted when this preparatory injection is followed by a subsequent intravenous injection of the filtrate. Single intravenous injections also are not productive of hemorrhage and thrombosis in lymph nodes.

scholarly journals STUDIES ON THE GENERALIZED SHWARTZMAN REACTION

1955 ◽  
Vol 102 (3) ◽  
pp. 249-261 ◽  
Author(s):  
Lewis Thomas ◽  
Joel Brunson ◽  
Richard T. Smith
Keyword(s):  
Polyvinyl Alcohol ◽  
Intravenous Injection ◽  
Dextran Sulfate ◽  
Nitrogen Mustard ◽  
Protective Action ◽  
Gram Negative ◽  
Single Intravenous Injection ◽  
Intravenous Injections ◽  
Shwartzman Reaction

Lesions indistinguishable from those of the generalized Shwartzman reaction occured in rabbits when a single intravenous injection of Gram-negative bacterial endotoxin was accompanied, or followed, by an injection of one of the following synthetic, heparin-like, acidic polymers-sodium polyanethol sulfonate, dextran sulfate, or sodium polyvinyl alcohol sulfonate. These reactions were produced by doses of polymer or of endotoxin which were without demonstrable effect when given singly. Heparin, in those similar to those previously shown to protect rabbits against the lesions of the generalized Shwartzman reaction, prevented the reaction to the combined injection of endotoxin and acidic polymers. Nitrogen mustard, which was previously shown to prevent the lesions of the generalized Shwartzman reaction from occurring after two intravenous injections of endotoxin, had no protective action against the lesions produced by the combined injection of endotoxin and polymer. Cortisone did not affect the reaction to endotoxin and polymer. The role of fibrinogen in the reaction under study is discussed in the paper which follows.

scholarly journals PLATELETS AND THE SHWARTZMAN PHENOMENON

1965 ◽  
Vol 121 (2) ◽  
pp. 235-246 ◽  
Author(s):  
Jack Levin ◽  
Leighton E. Cluff
Keyword(s):  
Intravenous Injection ◽  
Renal Lesions ◽  
Shwartzman Reaction ◽  
Hemorrhagic Lesion ◽  
Shwartzman Phenomenon

Studies are reported on the effect of immunologically induced thrombocytopenia upon the local and generalized Shwartzman phenomena. Intravenous injection of antiplatelet serum to rabbits produced profound but transient thrombocytopenia unaccompanied by significant changes in circulating leucocytes. Platelet antiserum alone given to rabbits prepared with thorotrast produced renal lesions characteristic of the Shwartzman reaction. Thrombocytopenia induced by platelet antiserum did not inhibit the cutaneous hemorrhagic lesion of the local Shwartzman phenomenon produced by sequential injections of endotoxin intracutaneously and intravenously. The implications of these observations in the pathogenesis of the local cutaneous and generalized Shwartzman reaction are discussed.

scholarly journals STUDIES ON THE GENERALIZED SHWARTZMAN REACTION

1952 ◽  
Vol 96 (6) ◽  
pp. 625-641 ◽  
Author(s):  
Robert A. Good ◽  
Lewis Thomas
Keyword(s):  
Intravenous Injection ◽  
Trypan Blue ◽  
Nitrogen Mustard ◽  
Skin Lesions ◽  
Intradermal Injection ◽  
Cortical Necrosis ◽  
Single Intravenous Injection ◽  
Shwartzman Reaction ◽  
Kidney Lesions ◽  
Local Shwartzman Reaction

Intravenous injection of thorotrast or trypan blue rendered rabbits susceptible to the production of bilateral cortical necrosis of the kidneys by a single intravenous injection of small amounts of meningococcal or Serratia marcescens toxin. This reaction was not produced when thorotrast or trypan blue were injected after toxin had been given. A single intradermal injection of toxin produced hemorrhagic skin lesions resembling the local Shwartzman reaction in rabbits given thorotrast 6 hours previously. These animals also developed bilateral cortical necrosis of the kidneys. When the order of injection was reversed, and thorotrast given after toxin, neither skin nor kidney lesions occurred. The skin and kidney lesions in thorotrast-treated rabbits were, like the local and generalized Shwartzman reactions, completely prevented by treatment with nitrogen mustard, in doses sufficient to produce polymorphonuclear leukopenia. The significance of these reactions, and their relationship to the previously described response to toxin in cortisone-treated rabbits, are discussed.

scholarly journals INHIBITION OF THE SHWARTZMAN PHENOMENON

1936 ◽  
Vol 63 (1) ◽  
pp. 59-68
Author(s):  
Tomio Ogata
Keyword(s):  
Clinical Significance ◽  
Intravenous Injection ◽  
Inhibitory Effect ◽  
Intradermal Injection ◽  
Shwartzman Phenomenon

The Shwartzman phenomenon can be inhibited by an intravenous injection of a potent bacterial filtrate within a few hours before or after the preparatory intradermal injection. The inhibitory effect is produced non-specifically by filtrates potent in the elicitation of the Shwartzman phenomenon, and it is of a transitory nature. The relation of the observation described to anaphylactic desensitization and to its clinical significance is discussed in this paper.

scholarly journals STUDIES ON THE GENERALIZED SHWARTZMAN REACTION

1953 ◽  
Vol 97 (6) ◽  
pp. 871-888 ◽  
Author(s):  
Robert A. Good ◽  
Lewis Thomas
Keyword(s):  
Intravenous Injection ◽  
Essential Role ◽  
Vascular Occlusion ◽  
Lethal Effect ◽  
Intradermal Injection ◽  
Cortical Necrosis ◽  
Hemorrhagic Necrosis ◽  
Shwartzman Reaction ◽  
Previously Treated ◽  
Glomerular Capillaries

In order to explore the hypothesis that the occurrence of thrombosis of small blood vessels is an essential stage in the development of the local and generalized Shwartzman reactions, the effect of heparin was studied. Aqueous heparin, administered intravenously, and "depot" heparin, injected subcutaneously, prevented completely the occurrence of the local and generalized Shwartzman phenomena. The amounts of heparin required for protection were similar to the amounts required to produce sustained incoagulability of the blood of rabbits for a period of at least 4 hours. The local and generalized Shwartzman reactions were prevented when heparin was given at the time of provocation, but not when heparin was administered during the period of preparation. Heparin prevented the development of bilateral cortical necrosis of the kidneys following a single intravenous injection of meningococcal toxin in rabbits previously treated with cortisone or thorotrast. Hemorrhagic necrosis of the skin which follows an intradermal injection of toxin in thorotrast-treated rabbits was also prevented by heparin. Provocation of the dermal Shwartzman reaction with glycogen, saline suspension of rabbit liver, and human serum was prevented by treatment with heparin. Heparin itself, in the preparations and dosages used, had no consistent effect on either white blood cell or platelet counts. Heparin had no effect on the occurrence of polymorphonuclear leukopenia which follows an intravenous injection of meningococcal toxin. Treatment with heparin did not interfere with the lethal effect of single, large doses of meningococcus toxin. In animals in which bilateral cortical necrosis of the kidneys was prevented by heparin, occlusion of the glomerular capillaries by "fibrinoid" material did not occur. These observations support the concept that vascular occlusion plays an essential role in the development of the local and generalized Shwartzman reactions.

scholarly journals STUDIES ON THE MECHANISM OF THE SHWARTZMAN PHENOMENON

1949 ◽  
Vol 89 (5) ◽  
pp. 461-478 ◽  
Author(s):  
Lewis Thomas ◽  
Chandler A. Stetson
Keyword(s):  
Intravenous Injection ◽  
Aerobic Glycolysis ◽  
Normal Skin ◽  
Intradermal Injection ◽  
Anaerobic Glycolysis ◽  
Rabbit Skin ◽  
High Degree ◽  
Shwartzman Phenomenon

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.

scholarly journals Whatever happened to the Shwartzman phenomenon?

2018 ◽  
Vol 24 (8) ◽  
pp. 466-479 ◽  
Author(s):  
Abdullah B Chahin ◽  
Jason M Opal ◽  
Steven M Opal
Keyword(s):  
Transplant Rejection ◽  
Hepatic Necrosis ◽  
Intradermal Injection ◽  
Control Mechanisms ◽  
Sterile Culture ◽  
Humoral Immune ◽  
Pathologic Features ◽  
Shwartzman Reaction ◽  
Shwartzman Phenomenon ◽  
Single Organ

Ninety years ago, Gregory Shwartzman first reported an unusual discovery following the intradermal injection of sterile culture filtrates from principally Gram-negative strains from bacteria into normal rabbits. If this priming dose was followed in 24 h by a second intravenous challenge (the provocative dose) from same culture filtrate, dermal necrosis at the first injection site would regularly occur. This peculiar, but highly reproducible, event fascinated the microbiologists, hematologists, and immunologists of the time, who set out to determine the mechanisms that underlie the pathogenesis of this reaction. The speed of this reaction seemed to rule out an adaptive, humoral, immune response as its cause. Histopathologic material from within the necrotic center revealed fibrinoid, thrombo-hemorrhagic necrosis within small arterioles and capillaries in the micro-circulation. These pathologic features bore a striking resemblance to a more generalized coagulopathic phenomenon following two repeated endotoxin injections described 4 yr earlier by Sanarelli. This reaction came to be known as the generalized Shwartzman phenomenon, while the dermal reaction was named the localized or dermal Shwartzman reaction. A third category was later added, called the single organ or mono-visceral form of the Shwartzman phenomenon. The occasional occurrence of typical pathological features of the generalized Shwartzman reaction limited to a single organ is notable in many well-known clinical events (e.g., hyper-acute kidney transplant rejection, fulminant hepatic necrosis, or adrenal apoplexy in Waterhouse-Fredrickson syndrome). We will briefly review the history and the significant insights gained from understanding this phenomenon regarding the circuitry and control mechanisms responsible for disseminated intravascular coagulation, the vasculopathy and the immunopathy of sepsis.

scholarly journals THE RELATION OF ALTERED LOCAL TISSUE REACTIVITY (SHWARTZMAN PHENOMENON) TO INFECTION AND INFLAMMATION

1937 ◽  
Vol 66 (5) ◽  
pp. 603-616
Author(s):  
Alan R. Moritz
Keyword(s):  
Intravenous Injection ◽  
Subcutaneous Injection ◽  
Local State ◽  
Local Tissue ◽  
Severe Inflammation ◽  
Infection And Inflammation ◽  
Shwartzman Reaction ◽  
Living Organisms ◽  
Shwartzman Phenomenon ◽  
Tissue Reactivity

Living B. aertrycke were effective in place of aertrycke filtrate as either the preparatory or the provocative injection in the production of a positive Shwartzman reaction. When living B. aertrycke were injected subcutaneously a more severe inflammation resulted, organization was delayed, and more living organisms survived at the site of inoculation in rabbits that had received 24 hours later an intravenous injection of B. aertrycke filtrate than was the case in similarly infected rabbits that had not received a subsequent injection of bacterial filtrate. When a local state of hypersusceptibility was created by the subcutaneous injection of B. aertrycke filtrate, the subsequent (24 hours) injection of living B. aertrycke led to the development at the site of subcutaneous preparation of a hemorrhagic necrosing inflammation in which the bacteria localized.

scholarly journals THE EXTENSION OF THE SHWARTZMAN PHENOMENON TO THE MOUSE AND SOME ECOLOGICAL DETERMINANTS OF THE SINGLE-INJECTION REACTION

1960 ◽  
Vol 112 (1) ◽  
pp. 167-186 ◽  
Author(s):  
William F. Arndt ◽  
Howard A. Schneider
Keyword(s):  
Single Injection ◽  
Inbred Mouse ◽  
Inbred Mouse Strain ◽  
Intradermal Injection ◽  
Bacterial Endotoxin ◽  
Gram Negative ◽  
Small Doses ◽  
Shwartzman Reaction ◽  
Antigen Antibody ◽  
Shwartzman Phenomenon

The localized Shwartzman reaction has been demonstrated in a highly inbred mouse strain (BSVS). This reaction was produced with marked regularity in these mice by administration of relatively small doses of bacterial endotoxin or other Shwartzman-active agents. It is considered the equivalent of the phenomenon described in the rabbit inasmuch as it has conformed to all the operational and histopathological aspects of the classical reaction that have been tested, including elicitation by various endotoxins, heterologous preparation and provocation, inhibition by anticoagulants, and provocation by antigen-antibody complexes. A reaction similar to the above but differing in its manner of production was also investigated and has been termed the single-injection Shwartzman reaction. This phenomenon was identical with the normal Shwartzman reaction in all ways except for the fact that it was elicited with but a single intradermal injection of bacterial endotoxin. In investigating the lesion it has been demonstrated that inapparent in the gross, but elicitible infection of the lungs with a Gram-negative microflora was uniformly associated with single-injection reactivity. Because of this constant association it has been suggested that a causal relationship exists between the infected state and the skin reaction, not on the basis of known immunological events but on the basis of the Shwartzman mechanism in which the lung flora, demonstrably excited by the preparative injection, appears to mediate natural "endogenous" provocation of the lesion at the prepared skin sites.

scholarly journals THE EFFECT OF CORTISONE ON THE SHWARTZMAN REACTION

1952 ◽  
Vol 95 (4) ◽  
pp. 409-428 ◽  
Author(s):  
Lewis Thomas ◽  
Robert A. Good ◽  
Keyword(s):  
Nitrogen Mustard ◽  
Intradermal Injection ◽  
Renal Lesion ◽  
Cortical Necrosis ◽  
Intravenous Injections ◽  
Pretreatment Period ◽  
Shwartzman Reaction ◽  
Systemic Symptoms ◽  
Schiff Reaction ◽  
Glomerular Capillaries

1. Cortisone, in a dose of 25 mg. daily and with a pretreatment period of 3 days, in rabbits weighing 1 to 1.5 kilos, did not inhibit the dermal Shwartzman reaction produced by meningococcal or S. marcescens toxin. 2. In cortisone-treated rabbits, a single intradermal injection of toxin produced a primary reaction of hemorrhage and necrosis in the skin at the injected site. This lesion resembled the Shwartzman reaction in its gross and histological appearance. 3. Like the Shwartzman reaction, the primary hemorrhagic reaction in cortisone-treated rabbits was prevented by nitrogen mustard, and the preventive effect of nitrogen mustard was partly eliminated when the femoral marrow was protected against the latter agent. 4. A single intravenous injection of meningococcal or S. marcescens toxin, in cortisone-treated rabbits, was followed by bilateral cortical necrosis of the kidneys in the majority of instances. The renal lesions, as well as hemorrhages in the lungs, spleen, liver, and gastrointestinal tract, resembled the lesions of the generalized Shwartzman reaction. Histologically, the glomerular capillaries in both types appeared to be occluded by homogeneous, eosinophilic material which showed a strongly positive Schiff reaction. 5. The renal lesion following a single injection of toxin in cortisone-treated animals, and that following two intravenous injections in the generalized Shwartzman reaction, were both completely prevented by nitrogen mustard. This effect of nitrogen mustard was inhibited when the femoral marrow was protected against the latter agent. 6. The injection of S. marcescens toxin into the skin of normal rabbits did not cause systemic symptoms, nor was it possible to provoke the generalized Shwartzman reaction by this route. In cortisone-treated rabbits, a similar intradermal injection was regularly followed by the development of bilateral cortical necrosis of the kidneys, indicating that absorption of toxin from the skin occurred in these animals. 7. Possible mechanisms to account for the observations are discussed. The authors are obliged to Professor James R. Dawson for many helpful suggestions during the course of this investigation.

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