Greater understanding of the underlying etiology and biology of breast cancer is enabling the clinical development of targeted therapies for metastatic breast cancer (MBC). Following the successful introduction of trastuzumab, the first human epidermal growth factor receptor (HER) biologically targeted therapy to become widely used in MBC patients, other agents have been developed. Novel agents include monoclonal antibodies such as pertuzumab, which bind to receptors on the cell surface, and tyrosine kinase inhibitors (TKIs) such as lapatinib, which target intracellular pathways such as that of the epidermal growth factor receptor. There is also growing clinical experience with antiangiogenic agents, particularly in combination with chemotherapy. These include the monoclonal antibody bevacizumab, which targets vascular endothelial growth factor receptor, and multitargeted TKIs with antiangiogenic and antiproliferative activities, such as sunitinib. Combination treatment with multiple agents targeting both the HER family and angiogenic pathways (e.g., trastuzumab plus bevacizumab) is also showing activity in the clinical setting. Despite recent advances, there are unanswered questions regarding the management of MBC with targeted agents. Future studies are necessary to determine the optimal combinations, doses, and schedules required to maximize clinical activity while minimizing toxicity. Despite the temptation to use a targeted agent in all patients, identification of patient subgroups most likely to benefit must be a key goal and will be critical to the successful future use of these treatments. The aim of this review is to summarize some of the key signaling pathways involved in tumor progression and some of the novel therapies that are in development for MBC.

Since the spring of 1981, more than 2300 cases of acquired immune deficiency syndrome (AIDS) have been reported from 41 states to the Centers for Disease Control. Cases also have been reported from 20 foreign countries, and reports are increasing at an alarming rate. More than 900 people (approximately 40 percent) have died of this disease. AIDS is characterized by skin test anergy to recall antigens, decreased T-helper subset, and inverted helper T-cell:suppressor T-cell ratios in the peripheral blood. Overt AIDS may be preceded by a prodrome that may last for many months and consists of fever, weight loss, and lymphadenopathy. The immune defect in AIDS permits the development of opportunistic infections caused by a number of organisms, including Pneumocystis carinii, Mycobacterium avium-intracellulare, Toxoplasma gondii, and various fungi. Certain malignancies also are associated with AIDS, in particular, Kaposi's sarcoma. Although the etiology of AIDS is unknown, the causative agent appears to be infectious. Lifestyle factors such as drug use and certain sexual activities may play a role. Currently, epidemiologists and others investigating the syndrome believe that AIDS can spread through sexual contact, blood products, or both. AIDS patients include homosexual males, users of intravenous drugs, immigrants from Haiti, hemophiliacs, female partners of males with AIDS, infants born to mothers who have AIDS, and persons who have received blood products from AIDS patients. Thus far, questions about AIDS outnumber the answers. Intensive research is being conducted to develop a rational approach to the treatment of AIDS and a better understanding of the relationship between the immune defense system and cancer.

No abstract

No abstract

The authors outline the quality indicators being developed by the Joint Commission on Accreditation of Health Care Organizations to compare hospital performance. The Joint Commission has provided several incentives to encourage antibiotic monitoring based on criteria derived from standard practice, as defined in the literature, and on the clinical judgment of the medical staff. In addition, the drug review process should be continuous and should encompass all areas of drug use in the hospital, including effectiveness in terms of disease outcome as well as cost efficiency. The authors discuss procedures under development in their institution to promote cost efficiency and informed discussion regarding clinical use of antibiotics on the formulary. Microbiology reporting, drug use, requests for nonformulary drugs, and unusual patterns of infection and sensitivities are tracked to identify problem areas and a feedback loop is used to inform the medical staff.