Discovery Medicine

Abstract: Coronary artery calcification (CAC) has long been known to occur as a part of the atherosclerotic process; recently it has been shown to be an active process resembling bone formation within the vessel wall. There is good evidence that the extent of CAC reflects the total coronary atherosclerotic burden and this has generated interest in using CAC as a marker of risk. The current consensus is that large amounts of CAC identify a patient highly vulnerable to future events. The advent of CT angiography added the ability to non-invasively detect critical luminal stenoses that are associated with a more immediate risk of events, and to visualize the non-calcified component of the atherosclerotic plaque. ... Read more

Abstract: Infectious agents contribute to the environmental factors involved in the development of autoimmune diseases possibly through molecular mimicry mechanisms. Hence, it is feasible that vaccinations may also contribute to the mosaic of autoimmunity. Evidence for the association of vaccinations and the development of these diseases is presented in this review. Infrequently reported post-vaccination autoimmune diseases include systemic lupus erythematosus, rheumatoid arthritis, inflammatory myopathies, multiple sclerosis, Guillain-Barré syndrome, and vasculitis. In addition, we will discuss macrophagic myofasciitis, aluminum containing vaccines, and the recent evidence for autoimmunity following human papilloma virus vaccine. ... Read more

Abstract: The APOE ε4 allele is associated with risk of late-onset Alzheimer's disease (AD). Longitudinal memory decline in asymptomatic APOE ε4 carriers shows greater acceleration compared with non-carriers, with a possible allele-dose effect, and begins prior to age 60. These results correlate with imaging and neuropathological studies that show AD-like changes at this age and collectively support the existence of a presymptomatic stage of AD. ... Read more

Abstract: Hemophilia A is an X-linked bleeding disorder caused by defective coagulation Factor VIII (FVIII). Although the efficacies of existing treatment using purified or recombinant FVIII are good, there remain shortcomings in using this particular form of treatment. A few FVIII gene therapy clinical trials have been initiated with modest improvements recorded, but these are no longer being continued due to insufficient efficacy. However, with the progress in the development of gene delivery vectors and the availability of mouse and canine hemophilia A models, gene therapy of hemophilia A remains an area of hot pursuit. ... Read more

Abstract: No chemotherapy regimen showed a survival benefit better than 5-fluorouracil alone in a phase III trial for advanced gastric cancer in 1990s, and several new cytotoxic agents became available in late 1990s. Thereafter, a couple of phase III trials supported the substitution of infusional 5-fluorouracil by orally administered agents and the replacement of cisplatin by oxaliplatin in early 2000s. Furthermore, a substantial amount of information about the heterogeneity and the biological backgrounds of gastric cancer has been obtained from recent trials, and it is suggested that some cytotoxic agents would be well indicated. Trastuzumab has succeeded in showing a survival benefit for patients with Her-2 positive gastric cancer which accounts for about 10-20% of the cancer. This means that the door is opened to the new era of chemotherapy with molecular target agents and with individualization for advanced gastric cancer. The new approach in the development of molecular target agents, e.g., biomarker oriented strategy, for advanced gastric cancer should be studied in clinical trials in the near future. ... Read more

Abstract: Mast cells (MC) are specialized exocytic cells that lie beneath the external surfaces of the body. For many decades, MCs were thought to primarily function as effector cells for IgE mediated allergic diseases. However, recent evidence indicates that MCs also function as important cells in immune surveillance. When activated by pathogens, MCs initiate innate and adaptive immune responses thereby resulting in protection against pathogens. The question remains if MC activation may also function in establishing immune responses against allergens and hence allergic disease. New studies suggest that MCs are not only the effector cell of allergy but may also be the initiator of allergy. ... Read more

Abstract: Ovarian cancer is the leading cause of cancer death among gynecological malignances. Despite the initial successful multimodality therapy with cytoreductive surgery and subsequent combination chemotherapy, most patients with advanced disease will ultimately relapse and become incurable. For this reason novel therapeutic approaches for the treatment of this malignancy are urgently needed. Adoptive transfer of genetically modified autologous tumor-reactive T cells is a promising novel antitumor therapy for many cancers. T cells may be genetically modified ex vivo to express chimeric antigen receptors (CARs), which are artificial T cell receptors targeted to specific tumor antigens. The resulting T cells are thus programmed to recognize tumor cells. Ovarian carcinomas in particular appear to be suited to this therapeutic approach based on the fact that these tumors are relatively immunogenic, inducing an endogenous T cell response. Furthermore, the degree to which this endogenous T cell mediated immune response is evident correlates to long-term patient prognosis following surgery and chemotherapy. To this end, adoptive T cell immunotherapy strategies for the treatment of ovarian carcinomas appear to be particularly promising and are currently being investigated at several centers in both pre-clinical and clinical settings. ... Read more

Abstract: Prostate cancer continues to represent a major health problem, and yet there is no effective treatment available for advanced metastatic disease. Thus, there is an urgent need for the development of more effective treatment modalities that could improve the outcome. Because prostate specific membrane antigen (PSMA), a transmembrane protein, is expressed by virtually all prostate cancers, and its expression is further increased in poorly differentiated, metastatic, and hormone-refractory carcinomas, it is a very attractive target. Molecules targeting PSMA can be labelled with radionuclides to become both diagnostic and/or therapeutic agents. The use of PSMA binding agents, labelled with diagnostic and therapeutic radio-isotopes, opens up the potential for a new era of personalized management of metastatic prostate cancer. ... Read more

Abstract: Most uveitics enjoy good vision despite potentially sight-threatening complications including cataract development. In those patients who develop cataracts, successful surgery stems from educated patient selection, careful surgical technique, and aggressive preoperative and postoperative control of inflammation. While commonly accepted in the adult patient population, recent investigations reflect the increased tolerance for primary intraocular lens placement in the pediatric cohort. The role of absolute control of inflammation continues with greater focus on immunomodulatory therapies. However, these agents bear their own side effect and complication profiles. Cataract extraction with intraocular lens implantation in the setting of meticulous control of inflammation can optimize visual outcome in adults and children with uveitis. ... Read more

Abstract: Capsule endoscopy is now recognized as the first line examination for patients with obscure bleeding and in selected patients with various small bowel diseases. A capsule endoscope has been designed for exploring the colon. Two pilot studies and one large multicenter trial have shown that the colon capsule is feasible and safe and provides encouraging data although its sensitivity for detecting colonic polyps is lower than optical colonoscopy. Technological improvements of the capsule and adaptation of the colon preparation are expected to increase the sensitivity of the colon capsule. ... Read more