Cortese, Denis A.

The pulmonary and renal vasculatures, in contrast to the systemic vasculature, constrict during hypoxia. The endothelium has been implicated in mediating these vascular responses to acute hypoxia via the production of endothelium-derived vasoactive factors. The present study, performed in anesthetized dogs, was designed to investigate the role of endothelium-derived relaxing factor (EDRF) to attenuate the vasoconstrictor response of the pulmonary and renal circulations during acute hypoxia. In response to hypoxia, pulmonary (2.2 +/- 0.3 to 4.5 +/- 0.6 mmHg.l-1.min) and renal (0.60 +/- 0.07 to 0.90 +/- 0.14 mmHg.ml-1.min) vascular resistances increased. Inhibition of endogenous EDRF with NG-monomethyl-L-arginine resulted in similar increases in pulmonary (3.0 +/- 0.1 to 4.8 +/- 0.4 mmHg.l-1.min) and renal (0.67 +/- 0.07 to 0.90 +/- 0.09 mmHg.ml-1.min) vascular resistances as in hypoxia. However, in the presence of both hypoxia and EDRF inhibition, an exaggerated pulmonary vascular response was observed (2.2 +/- 0.2 to 7.4 +/- 0.9 mmHg.l-1.min), in contrast to the renal vascular response to EDRF inhibition during hypoxia (0.61 +/- 0.05 to 0.95 +/- 0.10 mmHg.ml-1.min), which was not different from hypoxia or EDRF inhibition individually. The endothelium-derived contracting factor endothelin, which modestly increased during hypoxia (11.7 +/- 1.9 to 15.6 +/- 2.4 pg/ml), may also contribute to this vasoconstrictive response to hypoxia. This study suggests in the intact animal that EDRF serves to oppose the pulmonary vasoconstrictor response to hypoxia and further characterizes the role of endothelium-derived factors in the regulation of vascular function during hypoxia.

Hematoporphyrin derivative (HpD), a mixture of compounds chemically prepared from naturally occurring crude hematoporphyrin, is preferentially concentrated in neoplastic cells and produces red fluorescence when irradiated with blue‐violet light. In addition, HpD exhibits other photodynamic properties, which, in the presence of oxygen and visible light, result in cytotoxicity. Preliminary reports indicate that early, superficial carcinomas of the upper aerodigestive tract and tracheobronchial tree can be localized and treated successfully with HpD phototherapy (HpD‐PT), in which a fiberoptic bundle transmits laser light to the tumors. To assess this modality's potential for treating solid tumors, the cytotoxic effect of HpD‐PT was measured in a murine tumor model. We specifically assessed the effect of cooling on the pure photodynamic action of HpD‐PT. Adult female mice with typical mammary tumors received interstitial phototherapy 24 hours after HpD was given intraperitoneally. Light from an argon‐dye laser was delivered through an optical fiber, along with simultaneous cooling from a cryosurgical probe, for 15 minutes. After being cooled with a cryosurgical probe, tumors were excised 48 hours after treatment and the necrotic area was measured. The results indicate that cooling enhances the tumoricidal action of HpD‐PT.

AbstractRationale, aims and objectivesThe current health system in the United States is the result of a history of patchwork policy decisions and cultural assumptions that have led to persistent contradictions in practice, gaps in coverage, unsustainable costs, and inconsistent outcomes. In working toward a more efficient health system, understanding and applying complexity science concepts will allow for policy that better promotes desired outcomes and minimizes the effects of unintended consequences.MethodsThis paper will consider three applied complexity science concepts in the context of the Patient Protection and Affordable Care Act (PPACA): developing a shared vision around reimbursement for value, creating an environment for emergence through simple rules, and embracing transformational leadership at all levels.Results and conclusionsTransforming the US health system, or any other health system, will be neither easy nor quick. Applying complexity concepts to health reform efforts, however, will facilitate long‐term change in all levels, leading to health systems that are more effective, efficient, and equitable.

Coverage with evidence development and parallel review for molecular diagnostics aid regulation and reimbursement.