Rheumatoid arthritis and lymphoma: the role of disease-modifying anti-rheumatic drugs

A well-functioning immune system is of paramount importance in preventing lymphomagenesis. Both immunostimulation, which causes excessive cell turnover and increased potential for mutations, and immunosuppression, causing a decreased ability to monitor and halt aberrant cell proliferation, have been implicated in cancer development. Autoimmune diseases are characterized by excessive activation of lymphocytes due to a dysregulated response to self-antigens. The treatments for autoimmune disease therefore share a common goal of immunosuppression. While treatments have become better-targeted to specific inflammatory pathways over the last 30 years as opposed to general immunosuppression, there remains a high risk of hematologic malignancy for patients with autoimmune disease relative to the general population. There are numerous types of autoimmune disease, as well as much heterogeneity within each diagnosis from patient to patient. The focus of this thesis is Rheumatoid Arthritis (RA), a strikingly common disease affecting 0.5-1.0% of the world population and characterized by debilitating, painful, joint-deforming symptoms and difficulty in achieving remission. [1] Therapeutic intervention often necessitates a trial and error approach and various combinations of drugs, in the same way cocktails of chemotherapeutic drugs are tailored to treat cancers due to their heterogeneity. Drugs for the treatment of autoimmune diseases are collectively known as Disease-Modifying Anti-Rheumatic Drugs (DMARDs) and were only first widely used for the treatment of RA in the 1980s. This short history of widespread use, along with the great variability in manifestation of disease and treatment course, has historically limited the ability of observational studies to determine the safety of DMARDs in terms of malignancy risk. Only in the past few years has enough information been available, drawn mostly from national healthcare databases in several countries, to enable strong conclusions about the effects of DMARDs on malignancy risk. This thesis aims to provide a comprehensive review of the most recent and well-designed studies regarding currently available DMARDs for RA and their effects on the risk of lymphoma

Evangelicalism and Mental Slavery: A Miltonic Critique

In the 1960s, Billy Graham and Carl Henry heralded evangelical identity as the crusade that would bolster Christian witness in the modern age. Recent scholarship, however, has labeled the movement a dramatic disappointment. Historian D.G. Hart contends that mainstream Christianity has become so inclusive that the label “evangelical” has ceased to mean anything intelligible, and Mark Noll echoes this critique by labeling evangelicalism a “scandal of the mind.” Christianity’s greatest hope for global gospel witness has proved a dissapointment. One window into this evangelical failure may be found in the prose works of sixteenth century poet John Milton. Far from derived from modern concerns, the ecclesiastical and political turmoil of Milton’s day closely resembles the issue of evangelical identity in the twenty-first century, and the poet’s response applies well to Christianity’s contemporary situation. Milton’s critique of iconography, developed in his political tracts, reveals that mental slavery is the true scandal of the evangelical mind. While many scholars recognize the crisis of Christian identity in the twenty first century, Milton’s theory suggests that evangelicalism’s incompetence results from a failure to distinguish between the movement itself and the theological identity it signifies

Dostoevsky\u27s Polyphonic Apologetic: Dialogue and Defense of Christianity in The Brothers Karamazov

Although theologians today recognize the importance of apologetics, they struggle to find an approach that can advocate for Christianity amidst the postmodern shift in America. One such unexplored apologetic may be found in The Brothers Karamazov, a novel by the nineteenth century writer, Fyodor Dostoevsky. Since its publication in 1880, scholars have acclaimed this Russian novel for its masterful presentation of Christianity in literature. “Dostoevsky is to me both the greatest novelist, as such, and the greatest Christian storyteller, in particular, of all time,” writes theologian J.I. Packer (Packer). However, while critics like Packer correctly emphasize the theological nature of the novel, they consistently overlook its apologetic concerns. The central event of the text, the murder of Fyodor Pavlovich, does much more than raise questions concerning the meaning of life amongst the Karamazovs. More specifically, the crime ignites a central debate in which brothers Ivan and Alyosha draw from their respective worldviews of atheism and Christianity to offer conflicting explanations for the moral issues they face. This polemical structure of the novel suggests that Dostoevsky, himself a Christian, sought to engage in apologetics through his fiction writing