Publications

The requirement for precise geometric organization of endothelial cells and epithelial cells makes the gas-exchange region of the lung especially vulnerable to the adverse consequences of toxic products released from inflammatory cells. However, as a filter for large volumes of atmospheric gas, the lung is continually exposed to microorganisms and other toxic insults that require robust inflammatory defense. Enhanced production of extracellular matrix proteins is one important mechanism for restricting tissue damage, but excessive matrix production also has serious adverse effects on gas exchange. The amazing ability of the lung to recover from a barrage of environmental insults depends on precisely regulating both inflammation and extracellular matrix production in space and time. Below I review some of the evidence implicating members of the transforming growth factor beta family as critical mediators of this delicate dance and describe examples of how disruption of this balance by alterations in the magnitude of spatially restricted transforming growth factor beta activation can contribute to pathologic consequences of alveolar and airway injury and inflammation.

The Centers for Disease Control and Prevention in the U.S. Department of Health and Human Services is working with selected state and local health departments, academic centers, and others to develop an environmental public health tracking initiative to improve geographic and temporal surveillance of environmental hazards, exposures, and related health outcomes. The objective is to support policy strategies and interventions for disease prevention by communities and environmental health agencies at the federal, state, and local levels. The first 3 years of the initiative focused on supporting states and cities in developing capacity, information technology infrastructure, and pilot projects to demonstrate electronic linkage of environmental hazard or exposure data and disease data. The next phase requires implementation across states. This transition could provide opportunities to further integrate research, surveillance, and practice through attention to four areas. The first is to develop a shared and transparent knowledge base that draws on environmental health research and substantiates decisions about what to track and the interpretation of results. The second is to identify and address information needs of policy and stakeholder audiences in environmental health. The third is to adopt mechanisms for coordination, decision making, and governance that can incorporate and support the major entities involved. The fourth is to promote disease prevention by systematically identifying and addressing population-level environmental determinants of health and disease.

BACKGROUND

Many new agents are currently in trial in melanoma. It remains unclear, however, what the benefit of a given therapy may be since information on progression-free and overall survival of untreated patients is limited. Since few trials in melanoma have had a non-treated cohort, it remains unclear what survival can be expected in patients who are not treated with chemotherapy.

METHODS

To help develop parameters for future trials, we analyzed treatment history and survival in 212 patients with metastatic melanoma seen at our institution between January 1998 and September 2003. A retrospective analysis was done using a database created for melanoma patients at our center. Patient survival information was determined from this database, tumor registry, Social Security index, and direct patient calls. Patient staging information was determined according to the 2001 guidelines. Non-chemotherapy-treated patients with M1c disease were used as "controls."

RESULTS

The median survival of stage M1c melanoma was 6.0 months. Survival was longer for stage M1a and M1b and shorter in older patients. No significant differences were found in survival based on gender. Among chemotherapy-treated patients, those with progressive disease on treatment or with increased lactate dehydrogenase (LDH) fared worse than those with a clinical response or normal LDH, respectively. Patients treated with either biochemotherapy or temozolomide and thalidomide survived longer than those who received no chemotherapy treatment. Dacarbazine (DTIC) treatment did not prolong survival.

CONCLUSIONS

In this retrospective review of patients treated at a single institution, those treated with multiagent chemotherapy but not with single-agent DTIC appeared to have had a survival benefit.