Recombinant Factors for Hemostasis

Trauma deaths are a result of hemorrhage in 37% of civilians and 47% military personnel and are the primary cause of death for individuals under 44 years of age. Current techniques used to treat hemorrhage are inadequate for severe bleeding. Preliminary research indicates that fibrin sealants (FS) alone or in combination with a dressing may be more effective; however, it has not been economically feasible for widespread use because of prohibitive costs related to procuring the proteins. To meet future demands for hemostatic therapies, FS will likely include recombinant human fibrinogen (rFI) and recombinant human Factor XIII (rFXIII). The underlying hypothesis of the research presented in this dissertation is that a liquid fibrin sealant (LFS) composed of recombinant FI, FXIII and FIIa in optimized proportions can assist hemostasis in the presence and absence of a bioresorbable bandage while using considerably fewer biologics than commercial products currently available. This dissertation characterized rFI produced in the milk of transgenic cows, plasma-derived thrombin (pdFIIa) activated by sodium citrate and rFXIIIa expressed in genetically engineered Pichia pastoris with respect to their capacity to serve as components in a LFS. The ratios of these factors were optimized to yield a LFS with a rapid clot formation rate and high viscoelastic strength. This optimized LFS was preliminarily tested ex vivo and in vivo. The clotting kinetics and viscoelastic strength of our optimized LFS was equivalent to those of a commercially available LFS; however, it uses approximately 75% less fibrinogen and thrombin. Our optimal LFS successfully achieved hemostasis in a significant number of the wounds that included extensive tissue and vascular damage. LFS applied without the assistance of a dressing was able to stop bleeding of oozing wounds or those with small vessels; however, a scaffold was needed when wounds contained large vasculature.

Pissing Glass and the Body Crass: Adaptations of the Scatological in Théophile

Examination of scatological motifs in Théophile de Viau’s (1590-1626) libertine, or ‘cabaret’ poetry is important in terms of how the scatological contributes to the depiction of the Early Modern body in the French lyric.1 This essay does not examine Théophile’s portrait of the body strictly in terms of the ‘Baroque’ or the ‘neo-Classical.’ Rather, it argues that the scatological context in which he situates the body (either his, or those of others), reflects a keen sensibility of the body representative of the transition between these two eras. Théophile reinforces what Bernard Beugnot terms the body’s inherent ‘eloquence’ (17), or what Patrick Dandrey describes as an innate ‘textuality’ in what the body ‘writes’ (31), and how it discloses meaning. The poet’s scatological lyric, much of which was published in the Pamasse Satyrique of 1622, projects a different view of the body’s ‘eloquence’ by depicting a certain realism and honesty about the body as well as the pleasure and suffering it experiences. This Baroque realism, which derives from a sense of the grotesque and the salacious, finds itself in conflict with the Classical body which is frequently characterized as elegant, adorned, and ‘domesticated’ (Beugnot 25). Théophile’s private body is completely exposed, and, unlike the public body of the court, does not rely on masking and pretension to define itself. Mitchell Greenberg contends that the body in late sixteenth-century and early seventeenth-century French literature is often depicted in a chaotic manner because, ‘the French body politic was rent by tumultuous religious and social upheavals’ (62).2 While one could argue that Théophile’s portraits of a syphilis-ridden narrators are more a reflection of his personal agony rather than that of France as a whole, what emerges in Théophile is an emphasis on the movement, if not decomposition of the body.3 Given Théophile’s public persona and the satirical dimension of his work, it is difficult to imagine that the degeneration he portrays is limited only to his individual experience. On a collective level, Théophile reflects what Greenberg calls ‘a continued, if skewed apprehension of the world in both its physical and metaphysical dimensions’(62–3) typical of the era. To a large extent, the body Théophile depicts is a scatological body, one whose deterioration takes the form of waste, disease, and evacuation as represented in both the private and public domain. Of course, one could cast aside any serious reading of Théophile’s libertine verse, and virtually all of scatological literature for that matter, as an immature indulgence in the prurient. Nonetheless, it was for his dissolute behavior and his scatological poetry that Théophile was imprisoned and condemned to death. Consequently, this part of his work merits serious consideration in terms of the personal and poetic (if not occasionally political) statement it represents. With the exception of Claire Gaudiani’s outstanding critical edition of Théophile’s cabaret lyric, there exist no extensive studies of the poet’s libertine œuvre.4 Clearly however, these poems should be taken seriously with respect to their philosophical and aesthetic import. As a consequence, the objective becomes that of enhancing the reader’s understanding of the lyric contexts in which Théophile’s scatological offerings situate themselves. Structurally, the reader sees how the poet’s libertine ceuvre is just that — an integrated work in which the various components correspond to one another to set forth a number of approaches from which the texts are to be read. These points of view are not always consistent, and Théophile cannot be thought of as writing in a sequential manner along the lines of devotional Baroque poets such as Jean de La Ceppède and Jean de Sponde. However, there is a tendency not to read these poems in their vulgar totality, and to overlook the formal and substantive unity in this category of Théophile’s work. The poet’s resistance to poetic and cultural standards takes a profane, if not pornographic form because it seeks to disgust and arouse while denigrating the self, the lyric other, and the reader. Théophile’s pornography makes no distinction between the erotic and scatological. The poet conflates sex and shit because they present a double form of protest to artistic and social decency while titillating and attacking the reader’s sensibilities. Examination of the repugnant gives way to a cathartic experience which yields an understanding of, if not ironic delight in, one’s own filthy nature.