Resolution of experimental lung injury by monocyte-derived inducible nitric oxide synthase.

Although early events in the pathogenesis of acute lung injury (ALI) have been defined, little is known about the mechanisms mediating resolution. To search for determinants of resolution, we exposed wild type (WT) mice to intratracheal LPS and assessed the response at intervals to day 10, when injury had resolved. Inducible NO synthase (iNOS) was significantly upregulated in the lung at day 4 after LPS. When iNOS-/- mice were exposed to intratracheal LPS, early lung injury was attenuated; however, recovery was markedly impaired compared with WT mice. iNOS-/- mice had increased mortality and sustained increases in markers of lung injury. Adoptive transfer of WT (iNOS+/+) bone marrow-derived monocytes or direct adenoviral gene delivery of iNOS into injured iNOS-/- mice restored resolution of ALI. Irradiated bone marrow chimeras confirmed the protective effects of myeloid-derived iNOS but not of epithelial iNOS. Alveolar macrophages exhibited sustained expression of cosignaling molecule CD86 in iNOS-/- mice compared with WT mice. Ab-mediated blockade of CD86 in iNOS-/- mice improved survival and enhanced resolution of lung inflammation. Our findings show that monocyte-derived iNOS plays a pivotal role in mediating resolution of ALI by modulating lung immune responses, thus facilitating clearance of alveolar inflammation and promoting lung repair.

Routine, empathic and compassionate patient care: definitions, development, obstacles, education and beneficiaries.

RATIONALE: We believe that this study represents an innovative approach to clarifying the definitions of routine, empathic and compassionate health care, as well as of sympathy. We emphasize the importance of affective empathy and its intensification in the context of patient suffering (compassion), without abandoning the ideal of clinical equanimity. METHODS: We develop a pedagogical model for clinicians and trainees who are weaker in their empathic skills that includes four levels of growth. We clarify representative obstacles to empathic and compassionate care in education and clinical practice. We summarize the four beneficiaries of empathic and compassionate care (clinicians, patients, trainees, institutions). We suggest areas for future research, including the development of a compassion scale and conclude with a statement on how the conceptual and professional confusion we address adversely impacts patients and trainees. The article represents the consensus work of a group of health care professionals and students at Stony Brook University Hospital and School of Medicine who have been engaged in this project for several years through the Center for Medical Humanities, Compassionate Care, and Bioethics, established in August of 2008. CONCLUSIONS: We discern a shift away from concepts of clinical empathy and compassionate care that deny a significant place for an affective component and that idealize 'detachment'.