Tae-Sun Shim

Effect of alveolar recruitment maneuver in early acute respiratory distress syndrome according to antiderecruitment strategy, etiological category of diffuse lung injury, and body position of the patient.

ObjectiveTo assess how the level of positive end-expiratory pressure (PEEP) (antiderecruitment strategy), etiological category of diffuse lung injury, and body position of the patient modify the effect of the alveolar recruitment maneuver (ARM) in acute respiratory distress syndrome (ARDS). DesignProspective clinical trial. SettingMedical intensive care unit at a tertiary hospital. PatientsForty-seven patients with early ARDS, including 19 patients from our preliminary study. InterventionFrom baseline ventilation at a tidal volume of 8 mL/kg and PEEP of 10 cm H2O, the ARM (a stepwise increase in the level of PEEP up to 30 cm H2O with a concomitant decrease in the magnitude of tidal volume down to 2 mL/kg) was given with (ARM + PEEP, n = 20) or without (ARM only, n = 19) subsequent increase of PEEP to 15 cm H2O. In eight other patients, PEEP was increased to 15 cm H2O without a preceding ARM (PEEP only). Measurements and ResultsIn all three groups, Pao2 was increased by the respective intervention (all p < .05). In the ARM-only group, Pao2 at 15 mins after intervention was lower than Pao2 immediate after intervention (p = .046). In the ARM + PEEP group, no such decrease in Pao2 was observed, and Pao2 at 15, 30, 45, and 60 mins after intervention was higher than in the ARM-only group (all p < .05). Compared with the PEEP-only group, Pao2 of the ARM + PEEP group was higher immediately after intervention and at the later time points (all p < .05). Compared with patients with ARDS associated with direct lung injury (pulmonary ARDS), patients with ARDS associated with indirect lung injury (extrapulmonary ARDS) showed a greater increase in Pao2 (27 ± 21% vs. 130 ± 112%;p = .002) and a greater decrease in radiologic scores (1.0 ± 2.4 vs. 3.4 ± 1.5;p = .005) after the ARM. The increase in Pao2 induced by the ARM was greater for patients in the supine position than for patients in the prone position (61 ± 82% vs. 21 ± 14%;p = .028). Consequently, Pao2 immediately after the ARM was similar in the two groups of patients in different positions. ConclusionsAfter the ARM, a sufficient level of PEEP is required as an antiderecruitment strategy. Pulmonary ARDS and extrapulmonary ARDS may be different pathophysiologic entities. An effective ARM may obviate the need for the prone position in ARDS at least in terms of oxygenation.

Efficacy comparison between 18F-FDG PET/CT and bone scintigraphy in detecting bony metastases of non-small-cell lung cancer

BACKGROUNDnWe compared the efficacies of integrated whole-body (18)F-FDG PET/CT (PET/CT) and (99m)Tc-DPD bone scintigraphy (bone scan) for the detection of bone metastases in patients with non-small-cell lung cancer (NSCLC).nnnPATIENTS AND METHODSnBetween April 2004 and May 2007, the database at our institution was retrospectively reviewed to identify all patients with newly diagnosed NSCLC and who underwent staging with both PET/CT and bone scan prior to the initiation of therapy. Presence of bone metastases was confirmed by considering all available clinical information. This search identified 1000 patients, 265 women and 735 men (age range, 18-89 years; median age, 65 years).nnnRESULTSnBone metastases were confirmed in 105 (10.5%) patients. The respective accuracy, sensitivity, and specificity of PET/CT and bone scan in detecting bone metastases were 98.3% and 95.1% (p<0.001), 94.3% and 78.1% (p=0.001), and 98.8% and 97.4% (p=0.006). PET/CT also showed lower incidence of false positive (1.2% vs. 2.9%) and false-negative results (5.7% vs. 21.9%) than bone scan. Agreement between PET/CT and bone scan findings was good with calculated kappa=0.732.nnnCONCLUSIONSnPET/CT was superior to bone scan in the detection of bone metastases of NSCLC with the lower incidence of false-positive as well as false-negative results.

Chromosomal instability is a risk factor for poor prognosis of adenocarcinoma of the lung: Fluorescence in situ hybridization analysis of paraffin-embedded tissue from Korean patients.

BACKGROUNDnIn this study, we sought to evaluate the prognostic importance of chromosomal instability (CIN) in adenocarcinoma (AC) of the lung. The relationship between CIN detected by fluorescence in situ hybridization (FISH) and survival in AC patients was examined.nnnMETHODSnSixty-three surgical specimens of lung AC were analyzed. To identify tumors with CIN, p16 and multi-target DNA FISH assays for c-myc, chromosome 6, EGFR, and chromosome 5 (LAVysion, Vysis) were performed on nuclei extracted from paraffin-embedded tumor tissues. Survival rates were compared in terms of sex, age, histology, T factor, N factor, CIN, and smoking status. A sample was classified as CIN-positive if at least three of the five chromosomes were positive.nnnRESULTSnOut of the 63 specimens, 32 (39.7%) were CIN-positive. The 5-year overall disease-free survival rate was 58.7% as a whole, 46.9% for CIN-positive patients and 71.0% for the CIN-negative patients [hazard ratio (HR), 2.34; 95% confidence interval (CI), 1.04-5.26; p = 0.04]. The 5-year overall survival rate was 81.0%, 68.7% for CIN-positive patients and 93.5% for the CIN-negative patients (HR, 5.64; 95% CI, 1.23-25.70; p = 0.026). In multivariate analysis after adjusting for pathologic nodal staging, tumor staging, sex, age, and smoking history, compared with the CIN-negative patients, the CIN-positive status remained significantly associated with decreased overall survival (HR, 8.48; 95% CI, 1.66-43.42; p = 0.010).nnnCONCLUSIONSnCIN can be effectively detected in primary AC of lung using FISH analysis. CIN is associated with poor prognosis for AC, and may thus be utilized as an independent prognostic factor for the disease.

Green Tea Extract Inhibits Paraquat-Induced Pulmonary Fibrosis by Suppression of Oxidative Stress and Endothelin-l Expression

Paraquat-induced pulmonary fibrosis involves two factors, direct injury by oxygen free radicals and indirect injury by inflammatory cells and fibroblasts. Endothelin-1 (ET-1) has been shown to act as a mediator of pulmonary fibrosis, and its formation increases during oxidative stress. We investigated whether green tea extract (GTE), which has antioxidant properties, inhibits paraquat-induced pulmonary fibrosis and whether ET-1 is involved in this process. Paraquat (0.3 mg/kg) was instilled into the right lungs of rats, following which the rats were either not further treated (Group P, n = 7), or they were administered 1% GTE mixed with feed (Group PG; n = 7) or the ETA receptor antagonist ZD2574 (10 mg/kg through gavage; Group PZ; n = 7) for two weeks. As control, we used rats instilled with saline (Group N; n = 6). Two weeks after paraquat instillation, we assayed the degree of pulmonary fibrosis by light microscopic morphometry and hydroxyproline content; lipid peroxidation as a marker of oxidative stresses by measurement of malondialdehyde (MDA); ET-1 by immunohistochemistry; and prepro-ET-1 mRNA expression by reverse transcription-polymerase chain reaction. Compared with Group N, significant pulmonary fibrosis was observed in Group P, accompanied by increases in MDA, ET-1, and prepro-ET-1 mRNA expression. Compared with Group P, Group PG showed significant decreases in pulmonary fibrosis, along with decreases in MDA, ET-1, and prepro-ET-1 mRNA expression. We also observed significant decreases in pulmonary fibrosis in Group PZ compared with Group P. These findings suggest that GTE inhibits paraquat-induced pulmonary fibrosis by suppression of oxidative stress and ET-1 expression.

Physiologic characteristics of cold perfluorocarbon-induced hypothermia during partial liquid ventilation in normal rabbits

UNLABELLEDnBecause perfluorocarbon (PFC) liquid contacts closely with the alveolar capillaries during partial liquid ventilation (PLV), PLV with cold PFC may be used for the induction of hypothermia. Twenty rabbits were randomized to PFC-induced hypothermia (PH) (n = 7; core temperature 35 degrees +/- 1 degrees C), surface hypothermia (SH) (n = 7; 35 degrees +/- 1 degrees C), or normothermia (n = 6; 39 degrees +/- 1 degrees C). We induced PH by repeated in situ exchanges of 0 degrees C perfluorodecalin during PLV. At the establishment (0 min) of hypothermia in the PH group, oxygen consumption (P = 0.04) and oxygen extraction ratio (P = 0.01) decreased from normothermic condition. Metabolic (oxygen consumption, oxygen extraction ratio, serum lactate level) and hemodynamic variables (heart rate, blood pressure, cardiac output, pulmonary artery pressure) of the PH group were not different from those of the SH group at 0, 30, 60, 90, and 120 min of hypothermia. The difference in temperature between the pulmonary artery and rectum during the hypothermic period was smaller in the PH group compared with the SH group (P = 0.033). In conclusion, hypothermia may be induced during PLV by using cold PFC. This pulmonary method of cooling was comparable to a systemic method of cooling with regard to a few important physiologic variables, while maintaining a narrower interorgan temperature difference.nnnIMPLICATIONSnThe induction of moderate hypothermia was feasible in rabbits by administrating cold perfluorocarbon liquid into the lung. Physiologic changes induced by this pulmonary cooling were comparable to those induced by systemic cooling. Our method may be regarded as a methodological advance in the field of therapeutic hypothermia.

The effects of methylene blue on hemodynamic parameters and cytokine levels in refractory septic shock.

Background/Aims Endogenous nitric oxide (NO) induces the peripheral vasodilation via the activation of guanylate cyclase in patients with septic shock. The purpose of this study was to assess the acute effects of methylene blue (MB), which is an inhibitor of guanylate cyclase, on the hemodynamics and on the production of pro-inflammatory cytokines and nitric oxide (NO) in patients with refractory septic shock. Methods Twenty consecutive patients with refractory septic shock, which was defined as shock refractory to a dopamine infusion of more than 20 µg/kg/min with the appropriate use of antibiotics and adequate volume replacement, received MB infusion of 1 mg/kg intravenously. The hemodynamic and respiratory variables were measured at baseline, 30, 60 and 120 min after an infusion of MB (1 mg/kg). The blood levels of NO, IL-1, IL-10 and TNF-α were measured at baseline, 30 and 120 min after MB infusion. Results The administration of MB induced an increase in the systemic vascular resistance (SVR) that resulted in an increase of the mean arterial pressure (MAP) in patients with refractory septic shock, and this was without a decrease in cardiac output. The administered MB induced an increase in pulmonary vascular resistance (PVR) that resulted in an increase of pulmonary arterial pressure (PAP), without any deterioration of gas exchange. However, the increases in SVR and PVR were not associated with the alteration of endogenous production of NO, IL-1, IL-10 and TNF-α. Conclusion MB transiently elevated the MAP by increasing the SVR without altering the endogenous productions of NO, IL-1, IL-10 and TNF-α during the study period in patients with refractory septic shock.

Clinical characteristics of pulmonary arteriovenous malformations in Koreans

Although pulmonary arteriovenous malformations (PAVMs) are rare, they are important in clinical practice because they are associated with life‐threatening complications such as brain abscess, stroke and lung haemorrhage. The aims of the present study were to characterize PAVMs in a Korean population and to examine the incidence and factors associated with cerebral complications, which are a major cause of mortality.