Linking Research and Marketing: A Pharmaceutical Innovation

This chapter describes in very general terms the integration of clinical research and marketing, drawing on books by marketers and recent cases that have come to the public eye. The tools that have been used to accomplish this integration over the past half-century are various, but they all stem from a realization that in a rational world centered on health there need be no intrinsic divide between research and marketing. Most obviously, marketing drugs to physicians, who are professionals acting within their own spheres, depends crucially on research. Physicians respond, and need to see themselves as responding, to fact, figures, and studies. The well-chosen images and vehicles for marketing campaigns must be subordinated to research. Yet at the same time research is a means of increasing sales.

The pathophysiology of eosinophilic esophagitis: Altered mechanisms of antigen detection in the esophagus

Recently, a chronic idiopathic disease of the esophagus has emerged, which is now known as eosinophilic esophagitis (EoE). Incomplete knowledge regarding the pathogenesis of EoE has limited treatment options. EoE is known to be a Th2-type immune-mediated disorder. Based on previous studies in both patients and experimental models, it is possible that an abnormal reaction to antigen mediates the pathophysiology of EoE. In this thesis, symptoms and signs unique to EoE were identified by an age-matched, case-controlled study of 326 patients with EoE and gastroesophageal reflux disease. The molecular mechanisms involved in antigen detection in the esophagus, in relation to EoE were then investigated. Esophageal epithelial cells were found, for the first time, to be capable of acting as non-professional antigen presenting cells, with the ability to engulf, process and present antigen on MHC class II to T helper lymphocytes. Antigen presentation by esophageal epithelial cells was induced by interferon-γ, which is increased in biopsies from patients with EoE. Next, it was discovered that esophageal epithelial cell lines expressed functional toll-like receptor (TLR) 2 and TLR3, but in esophageal mucosal biopsies only infiltrating immune cells (including eosinophils) expressed TLR2 and TLR3. Finally, the potential involvement of IgE in the pathogenesis of esophageal inflammation was investigated. IgE in the esophagus was found to be present on mast cells, which are increased in density in the esophageal mucosae of patients with EoE and especially those with a history of atopy. Mechanisms of antigen detection may mediate the pathophysiology of EoE in the esophagus through antigen presentation by epithelial cells, detection by TLRs on immune cells and detection through IgE on mucosal mast cells. Together, these findings demonstrate that mechanisms of antigen detection may actually contribute to the pathophysiology of EoE. Through increased understanding of the mechanisms of EoE, the results of this thesis may contribute to future therapy.

Multinational Management

This book is designed to help the reader understand the rationale of multinational corporations. Each of the nine central chapters focuses on the question of how a centrally directed multinational corporation (called a geocentric) can earn more profit than an identical corporation which lacks central direction (called a polycentric). Although some central direction is usually good, too much can be bad: Other multinationals (called ethnocentric) straitjacket their subsidiaries into acting in ways appropriate only in the headquarters' nation.