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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.

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This essay examines the development of Andrew Jackson's ideas about nationalism, citizenship, and sovereignty within the southern borderlands of the post-Revolutionary United States. It argues that he was in many respects a conventional borderlands leader-that is, someone with little sense of attachment to any particular polity, who speculated in Indian lands while pursuing commercial ventures through American, Spanish, and Native jurisdictions. But an especially devastating war between the settlers of Middle Tennessee and some Cherokee warriors during the 1790s forced Jackson and others to articulate their attachment to the United States in new ways. Bitterly rejecting a Federalist model of citizenship that assumed clear territorial limits, they invented a new "protection covenant," whereby the people themselves, imagined within a brutal state of nature, retained full sovereignty to deploy violence. In addition to a fresh look at Jackson, the article demonstrates the importance of international as well as Constitutional law in the formation of early American nationalism.

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