scholarly journals STUDIES ON THE GENERALIZED SHWARTZMAN REACTION

1953 ◽  
Vol 97 (5) ◽  
pp. 751-766 ◽  
Author(s):  
Lewis Thomas ◽  
Floyd W. Denny ◽  
Joan Floyd
Keyword(s):  
Time Interval ◽  
Time Of Death ◽  
Fibrinoid Necrosis ◽  
Optimal Conditions ◽  
Cortical Necrosis ◽  
Intravenous Injections ◽  
Hemorrhagic Necrosis ◽  
Group A ◽  
Shwartzman Reaction ◽  
Systemic Infections

Cutaneous and systemic infections of rabbits by Group A streptococci bring about a state of preparation for, respectively, the local and generalized Shwartzman reactions, produced by intravenous injection of meningococcal or S. marcescens toxin. With maximal systemic streptococcal infections, the lesions of the generalized Shwartzman reaction do not differ from those caused by two successive intravenous injections of Gram-negative bacterial toxins. The characteristic lesions of the reaction are bilateral cortical necrosis of the kidneys, hemorrhagic necrosis in the lungs, liver, and spleen, and myofiber necrosis in the myocardium. Under optimal conditions involving the dosages of streptococci and toxin, and the time interval between the injections, a new lesion consisting of necrosis and the accumulation of fibrinoid material in the walls of the coronary arteries occurred in approximately 50 per cent of animals within 48 hours after the injection of meningococcal toxin. Fibrinoid necrosis was not observed in the arteries of tissues other than the heart. It did not occur in control rabbits injected with streptococci alone or toxin alone, nor in animals with the generalized Shwartzman reaction produced by two intravenous injections of toxin. Streptococcal bacteriemia was present at the time of death in one-third of the animals with fibrinoid necrosis. In one animal, a group of bodies resembling cocci in chains was seen within the wall of a coronary artery with fibrinoid necrosis. A series of photomicrographs to illustrate the pathological changes in the hearts and kidneys of streptococcus-infected rabbits subjected to the Shwartzman reaction is presented.

scholarly journals STUDIES ON THE GENERALIZED SHWARTZMAN REACTION

1952 ◽  
Vol 96 (6) ◽  
pp. 605-624 ◽  
Author(s):  
Lewis Thomas ◽  
Robert A. Good
Keyword(s):  
Nitrogen Mustard ◽  
Lethal Effect ◽  
Optimal Time ◽  
Time Interval ◽  
Renal Lesion ◽  
Protein Nitrogen ◽  
Local Skin ◽  
Cortical Necrosis ◽  
Before And After ◽  
Shwartzman Reaction

Certain factors involved in the production of the generalized Shwartzman reaction with meningococcal toxin in rabbits were investigated. The optimal amounts of toxin for the preparing and provoking injections, and the optimal time interval between injections were determined. Under suitable conditions of dosage and timing, bilateral cortical necrosis of the kidneys was produced in a high proportion of animals. When excessive amounts of toxin were used for preparation the incidence of the reaction was reduced. Animals undergoing the generalized Shwartzman reaction became severely prostrated within several hours after the provoking injection of toxin. The renal lesion became fully developed within 24 hours, and its occurrence was associated with a rise of the blood non-protein nitrogen. Edema and petechial hemorrhages in the ears were observed in rabbits with advanced renal lesions. The earliest change in the kidneys in the generalized Shwartzman reaction was the appearance of homogeneous, eosinophilic material, resembling fibrinoid, within the lumen of the glomerular capillaries. Occlusion of the capillaries by this material was regarded as the cause of subsequent tubular necrosis in the renal cortex. The material appeared to be derived from the blood, rather than from the capillary walls. Cortisone enhanced the lethal effect of a single, large dose of meningococcal toxin, as well as causing bilateral renal cortical necrosis. The generalized Shwartzman reaction produced by two injections of toxin was aggravated by cortisone and ACTH. Profound polymorphonuclear leukopenia was produced by both the preparing and provoking injections of toxin. When leukopenia was produced before the preparing injection of toxin, by treatment with nitrogen mustard, the generalized Shwartzman reaction was inhibited. During the intervals before and after leukopenia, and when leukopenia was prevented by shielding the femoral bone marrow from the action of nitrogen mustard, no inhibition of the generalized Shwartzman phenomenon was demonstrable. Various colloidal and particulate materials, which are capable of provoking the local skin Shwartzman reaction when injected intravenously, failed to provoke the generalized Shwartzman reaction. A working hypothesis was set up to account for certain events in the generalized Shwartzman reaction.

scholarly journals THE PREVENTION OF THE GENERALIZED SHWARTZMAN REACTION WITH SODIUM WARFARIN

1958 ◽  
Vol 107 (3) ◽  
pp. 377-381 ◽  
Author(s):  
Sandor S. Shapiro ◽  
Donald G. McKay
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Control Group ◽  
Cortical Necrosis ◽  
Renal Cortical Necrosis ◽  
Intravascular Coagulation ◽  
Intravenous Injections ◽  
Bacterial Endotoxins ◽  
Shwartzman Reaction ◽  
Kidney Liver ◽  
Intravenous Sodium

Using intravenous sodium warfarin, rabbits were rendered hypoprothrombinemic and subjected to two intravenous injections of Shear's polysaccharide. None of the 9 animals surviving the required period of time developed bilateral renal cortical necrosis or histologic thrombi in the kidney, liver, spleen, or lungs. In a control group of 7 animals treated only with endotoxin, 6 developed bilateral renal cortical necrosis. It is concluded that the prothrombin complex is necessary for the production of the generalized Shwartzman reaction by bacterial endotoxins and that this phenomenon is essentially a process of disseminated intravascular coagulation.

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 HOST-PARASITE FACTORS IN GROUP A STREPTOCOCCAL INFECTIONS

1960 ◽  
Vol 111 (2) ◽  
pp. 255-284 ◽  
Author(s):  
Dennis W. Watson
Keyword(s):  
Scarlet Fever ◽  
Intravenous Injections ◽  
Streptolysin O ◽  
Bacterial Endotoxins ◽  
Group A ◽  
Shwartzman Reaction ◽  
Host Parasite ◽  
Parasite Factors ◽  
Pyrogenic Activity

The factors present in streptococcal lesion extracts (SLE) which enhanced the lethal and tissue-damaging properties of Gram-negative bacterial endotoxins and streptolysin O were identified with the scarlet fever group of toxins. Toxic manifestations attributed to this group of toxins included lethality, cardiotoxic and other tissue damage, enhancement of toxicity, and pyrogenicity. Of these, the measurement of febrile response in American Dutch rabbits was the most useful parameter of toxicity. In rabbits, repeated daily intravenous injections of 0.125 Lf of a purified erythrogenic toxin immunizes specifically against the pyrogenic activity; this technique was used to type the toxins and to distinguish them from exogenous and endogenous pyrogens; non-specific pyrogens, such as streptococcal endotoxin, were not found in SLE. All types of the Lancefield Group A streptococci tested produced one or or more immunologically distinct toxins in vivo in contrast to Groups B and C which did not produce them; toxins A and B, previously distinguished by neutralization of rash-inducing activity in the skin, were produced in vivo. The A toxin was the most common, as indicated by its presence in extracts prepared with Types 28, 12, 17, and 10 (NY-5); B toxin was found in 10 (NY-5) and 19. A new toxin, designated C, was obtained from a Type 18. In American Dutch rabbits, purified toxin at a concentration of 15 Lf (900,000 STD) neither gave a Dick test nor prepared the skin for the local Shwartzman reaction; by this route, however, in contrast to classical endotoxins, they enhance the lethal and tissue-damaging properties of sublethal doses of these and other toxins. These properties of the immunologic distinct exotoxins as demonstrated in American Dutch rabbits suggest by analogy their importance in the pathogenesis of streptococcal disease in man. Evidence that might implicate them in sequelae, in addition to scarlet fever, is discussed.

Spontaneous Bilateral Renal Cortical Necrosis in Animals

1967 ◽  
Vol 4 (3) ◽  
pp. 233-244 ◽  
Author(s):  
K. Nordstoga
Keyword(s):  
Vascular Lesion ◽  
The Other ◽  
Vascular Lesions ◽  
Fibrinoid Necrosis ◽  
Autopsy Material ◽  
Cortical Necrosis ◽  
Renal Cortical Necrosis ◽  
Renal Vessels ◽  
Shwartzman Reaction ◽  
Afferent Arterioles

Six cases representing three species, previously diagnosed as bilateral renal cortical necrosis (BCN), were studied histologically. One horse had vascular lesions including fibrinoid necrosis and fibrinous thrombi in various organs. Intrarenally these lesions occurred in interlobular arteries, afferent arterioles, and glomeruli. Another horse had bilateral renal glomerular thrombosis but no extra-glomerular vascular lesion. Distinct fibrinous deposition in the renal vessels did not occur among the other four cases. A comparison is drawn between the characteristic lesions in the generalized Shwartzman reaction (GSR) and BCN as diagnosed in our autopsy material. The renal alterations were compatible with GSR in two horses only among the six cases.

Effect of Anticoagulating and Non-Anticoagulating Concentrations of Heparin on the Generalized Shwartzman Reaction

1970 ◽  
Vol 24 (01/02) ◽  
pp. 136-145 ◽  
Author(s):  
J. J Corrigan
Keyword(s):  
Dose Group ◽  
Blood Platelets ◽  
Coagulation Factors ◽  
Renal Lesion ◽  
Fibrin Deposition ◽  
Cortical Necrosis ◽  
Renal Cortical Necrosis ◽  
Intravenous Injections ◽  
Shwartzman Reaction

SummaryRabbits given 2 properly spaced intravenous injections of bacterial endotoxin develop bilateral renal cortical necrosis (generalized Shwartzman reaction - gSr). This renal lesion is the result of fibrin deposition secondary to diffuse intravascular clotting (DIC). Using this experimental model, the effect of anticoagulating (large) and non- anticoagulating (small) concentrations of heparin on the changes in blood platelets, plasma coagulation factors II, V, VIII and fibrinogen during the production of renal cortical necrosis was studied. The data demonstrate that all amounts of heparin given during, but not after, the period of intravascular clotting reduced the frequency of renal cortical necrosis. Anticoagulating concentrations completely prevented the renal lesion. Non-anticoagulating amounts could reduce the frequency of the renal lesions, but this effect was not predictable or consistent. Coagulation studies in the large dose group revealed thrombocytopenia reduced factors II, V, and VIII but no fibrinogen consumption. These findings suggest that heparin inhibits the formation of fibrin in vivo, thereby preventing the formation of renal cortical necrosis. The coagulation data in the small dose group differed in that fibrinogen consumption did occur. The possible explanations for the phenomenon were discussed.

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.

Liquoid Induced Stasis and the Generalized Shwartzman Reaction

1979 ◽  
Vol 41 (04) ◽  
pp. 804-810 ◽  
Author(s):  
Knut Nordstoga
Keyword(s):  
Red Cells ◽  
Renal Lesions ◽  
Intravenous Injections ◽  
Shwartzman Reaction ◽  
Glomerular Capillaries

SummaryThe composition of the occlusive material within dilated glomerular capillaries, following intravenous injections of Liquoid in blue foxes, was studied electron microscopically; it was found that it mainly consisted of a debris in which disintegrated red cells constituted the major component. Damaged platelets and necrotic endothelial remnants were other components. These observations were interpreted as a result of glomerular stasis, and it was concluded that stasis in glomerular capillaries is a basic event in the development of the renal lesions accompanying the generalized Shwartzman reaction.

Studies on the Pathogenesis of the Generalized Shwartzman Reaction

1964 ◽  
Vol 12 (02) ◽  
pp. 462-470 ◽  
Author(s):  
F Rodríguez-Erdmann
Keyword(s):  
Fibrinolytic System ◽  
Factor V ◽  
Morphological Pattern ◽  
Cortical Necrosis ◽  
G Factor ◽  
Conventional Form ◽  
Renal Cortical Necrosis ◽  
Shwartzman Reaction

SummaryAnimals treated in the conventional form to elicit the generalized Shwartzman reaction (gSr) by means of properly spaced injections of endotoxin develop an abrupt consumption of the plasmatic factors of the clotting mechanism, as demonstrated by the reduction of the activity of prothrombin and Ac-G (factor V). These animals show ultimatly characteristic morphological pattern: bilateral cortical necrosis of the kidney. Rabbits treated four hours after the second (‘‘provocative”) endotoxin injection with streptokinase (Varidase/Lederle) in order to activate the fibrinolytic system failed to develop the renal cortical necrosis, but their prothrombin and Ac-G (factor V) level decreased abruptly.Through indirect deduction the intravascular presence of thrombin-like activity is accepted four hours after the “provocative” endotoxin injection.

scholarly journals SIMILARITY OF HOST RESPONSES ELICITED BY POLYSACCHARIDES OF ANIMAL AND PLANT ORIGIN AND BY BACTERIAL ENDOTOXINS

1957 ◽  
Vol 106 (1) ◽  
pp. 77-97 ◽  
Author(s):  
Maurice Landy ◽  
Murray J. Shear ◽  
Keyword(s):  
Host Responses ◽  
Mouse Tissue ◽  
Rabbit Skin ◽  
Biological Phenomena ◽  
Hemorrhagic Necrosis ◽  
Bacterial Endotoxins ◽  
Shwartzman Reaction ◽  
Sarcoma 37 ◽  
Kidney Liver ◽  
Plant Sources

Ten polysaccharides, isolated from various animal and plant sources, were selected for comparison with 2 bacterial polysaccharides, typical of Gram-negative endotoxins. The tissue sources were: mouse (kidney, liver, lung, stomach, Sarcoma 37, and Carcinoma 241-6); rabbit skin and chick embryo skin; and tangerine and Bryonia root. The bacterial endotoxins were those of S. typhosa and Serr. marcescens. Their relative potency was determined in inducing the following host effects: fever, tolerance to pyrogenic action, leucocytic changes, the Shwartzman reaction, damage to Sarcoma 37, dermal hemorrhagic-necrosis by epinephrine, enhancement of antibody production, and lethality. Some of the polysaccharides were consistently active in all the host reactions studied; except for pyrogenic activity at high dosage, the other polysaccharides were consistently negative throughout. The mouse tissue polysaccharides elicited all the effects studied; in some instances their potency approached those of the bacterial polysaccharides. It is pointed out that elicitation of the above array of biological phenomena, hitherto considered characteristic of bacterial endotoxins, can be obtained with polysaccharides from animal and plant tissues.

Sign in / Sign up

Export Citation Format

Share Document