Intraoperative ultrasonographic localization of pulmonary ground-glass opacities

ObjectivesGround-glass opacities are typically difficult to inspect and to palpate during video-assisted thoracic surgery. We therefore examined whether ultrasonographic assessments could localize ground-glass opacities and help to achieve adequate resection margins.MethodsAn intraoperative ultrasonographic procedure was prospectively performed on 44 patients harboring ground-glass opacities of less than 20 mm in diameter to localize these lesions and to achieve adequate margins. We also examined whether there were any complications resulting from the intraoperative ultrasonogram, such as lung injury, heart injury, or arrhythmia. We excluded patients with both asthma and chronic obstructive pulmonary disease from this study inasmuch as the intraoperative ultrasonographic procedure is more difficult to interpret when residual air is present in the lung.ResultsA total of 53 ground-glass opacities were successfully identified by intraoperative ultrasonography without any complications. Of the 20 mixed ground-glass opacities that we examined, 15 were found on palpation. However, only 4 (12.1%) of the 33 pure ground-glass opacities could be palpated. In all instances in which complete collapse of the lung was achieved (30/53 of these cases), high-quality echo images were obtained. Additionally, a strong correlation was found between the resection margins measured by ultrasonogram and the margins determined by histologic examination in the resected lung specimens (r2 = 0.954, P < .001).ConclusionsIntraoperative ultrasonography can both safely and effectively localize pulmonary ground-glass opacities in a completely deflated lung. This procedure is also useful for the evaluation of surgical margins in a resected lung. Hence, ultrasonography may assist surgeons to perform minimally invasive lung resections with clear surgical margins during the treatment of solitary lung ground-glass opacity

Pathophysiology of acute graft-versus-host disease

Graft-versus-host disease (GVHD) has been the primary limitation to the wider application of allogeneic bone marrow transplantation (BMT). The pathophysiology of acute GVHD is complex and can be conceptualized to be a three-step process based on murine studies. In step 1, the conditioning regimen leads to the damage and activation of host tissues and induces the secretion of inflammatory cytokines. As a consequence, the expression of MHC antigens and adhesion molecules is increased enhancing the recognition of host alloantigens by donor T cells. Donor T-cell activation in step 2 is characterized by donor T cell interaction with host APCs and subsequent proliferation, differentiation and secretion of cytokines. Cytokines such as IL-2 and IFN-Γ enhance T-cell expansion, induce cytotoxic T cells (CTL) and natural killer (NK) cell responses and prime additional mononuclear phagocytes to produce TNF-Α and IL-1. These inflammatory cytokines in turn stimulate production of inflammatory chemokines, thus recruiting effector cells into target organs. In step 3, effector functions of mononuclear phagocytes are triggered via a secondary signal provided by lipopolysaccaride (LPS) that leaks through the intestinal mucosa damaged during step 1. This mechanism may result in the amplification of local tissue injury and further promotion of an inflammatory response, which, together with the CTL and NK components, leads to target tissue destruction in the transplant host. The following review discusses the three-step process of the pathophysiology of experimental acute GVHD. Copyright © 2003 John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34866/1/716_ftp.pd

Induction of oxidative stress biomarkers following whole-body irradiation in mice.

Dose assessment is an important issue for radiation emergency medicine to determine appropriate clinical treatment. Hematopoietic tissues are extremely vulnerable to radiation exposure. A decrease in blood cell count following radiation exposure is the first quantitative bio-indicator using hematological techniques. We further examined induction of oxidative stress biomarkers in residual lymphocytes to identify new biomarkers for dosimetry. In vivo whole-body radiation to mice exposed to 5 Gy significantly induces DNA double-strand breaks, which were visualized by γ-H2AX in mouse blood cells. Mouse blood smears and peripheral blood mononuclear cells (PBMC) isolated from irradiated mice were used for immunostaining for oxidative biomarkers, parkin or Nrf2. Parkin is the E3 ubiquitin ligase, which is normally localized in the cytoplasm, is relocated to abnormal mitochondria with low membrane potential (ΔΨm), where it promotes clearance via mitophagy. Nrf2 transcription factor controls the major cellular antioxidant responses. Both markers of oxidative stress were more sensitive and persistent over time than nuclear DNA damage. In conclusion, parkin and Nrf2 are potential biomarkers for use in radiation dosimetry. Identification of several biological markers which show different kinetics for radiation response is essential for radiation dosimetry that allows the assessment of radiation injury and efficacy of clinical treatment in emergency radiation incidents. Radiation-induced oxidative damage is useful not only for radiation dose assessment but also for evaluation of radiation risks on humans