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This study confirms that botulinum neurotoxin type A (BoNT-A) decreases capsular contracture and elucidates a possible mechanism. Silicone blocks were implanted subcutaneously in 20 mice. The experimental groups received BoNT-A (1, 2·5 or 5 U) instilled into the subcutaneous pocket. After 30 days, periprosthetic capsules were harvested and evaluated. The effect of BoNT-A on the differentiation of human dermal fibroblasts to myofibroblasts in culture was examined by Western blot analysis. Changes in transforming growth factor-beta1 (TGF-β1) expression in cultured fibroblasts were determined by enzyme-linked immunosorbent assay (ELISA). In in vivo study, the thickness of capsules (P < 0·05) and the number of alpha-smooth muscle actin (α-SMA)(+) cells in capsules (P < 0·05) were significantly decreased in the experimental groups. TGF-β1 was significantly underexpressed in the experimental groups (P < 0·05). In in vitro study, BoNT-A did not significantly affect fibroblast viability. Western blot analysis showed that α-SMA protein levels were significantly decreased in the experimental groups (P < 0·05). Based on ELISA, the amount of TGF-β1 was significantly decreased in the experimental groups (P < 0·05), especially cells treated with a high dose of BoNT-A (P < 0·001). This study confirms that BoNT-A prevents capsular formation around silicone implants, possibly by blocking TGF-β1 signalling and interrupting the differentiation of fibroblasts to myofibroblasts.

UNLABELLED Because 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. IMPLICATIONS The 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.

We evaluated general office chair and adjustable chairs which can adjust to fit each person. We also analyzed how each design dimension was reached and affected the human body by objective EMG (Electromyogram) evaluation, and by subjective evaluation of physical discomfort and comfort. Studies like this will be very important in the database. The purpose of this study is on upgrading the physical comfortableness, eliminating users' complaints about previous chairs.

Background: In partial liquid ventilation (PLV), the nondependent lung was observed to be inflated first and the dependent lung later. The inflational time difference between the lung regions can lead to maldistribution of tidal gas and inefficient gas bubbling in the slow-inflating region during PLV. In this situation, increasing the inspiratory to expiratory (I:E) ratio of the mechanical ventilator would lessen the heterogeneity of regional ventilation and improve gas exchange possibly to a greater degree than in gas ventilation (GV). Design and setting: Animal study at the Asan Institute for Life Sciences, Seoul, Korea Subjects: Eighteen rabbits (2.6 6 0.5 kg) with acute lung injury by saline solution lavage. Interventions: Three I:E ratios were tried in GV and then in PLV. I:E ratios were changed by adjusting pause (1:2, 1:1, and 2:1; group 1) or by adjusting inspiratory flow rate (1:3, 1:1, and 2:1; group 2). Measurements and results: With increasing I:E ratio in all animals, PaO2/FIO2 increased (80 6 24, 143 6 74, and 147 6 88 mm Hg; p 5 0.001), and PaCO2 decreased (74 6 15, 66 6 16, and 66 6 15 mm Hg; p 5 0.006). The increases of PaO2/FIO2 from 1:2/1:3 to 1:1 (p 5 0.006) and from 1:1 to 2:1 (p 5 0.036) were both greater in group 1 than in group 2. PaCO2 decreased with increasing I:E ratio in group 1, but not in group 2. The change of PaO2/FIO2 by varying the I:E ratio was 49 6 65% in PLV and 14 6 14% in GV (p 5 0.003). Conclusions: Extending the I:E ratio, especially by adding pause, improved gas exchange in PLV. Oxygenation in PLV was affected by the I:E ratio to a greater degree than in GV. (CHEST 1999; 116:1032‐1038)

The pharmacokinetics of a non-narcotic analgesic, DA-5018, were compared after single intravenous (i.v.), subcutaneous (s.c.), and oral administrations, and after multiple (seven consecutive days) s.c. administration to rats. After i.v. administration of DA-5018, 1, 2, and 5 mg kg-1, the pharmacokinetic parameters of DA-5018 were independent of the dose ranges studied. After oral administration of DA-5018, absorption of the drug from gastrointestinal (GI) tract was fast, but the extent of absolute bioavailability (F) was low; the values were 23.2, 23.0, and 27.3% for 2, 5, and 10 mg kg-1, respectively. After single s.c. administration of DA-5018, absorption of the drug from the injected site was fast and the extent of absorption was fairly good; the F values were 74.5 and 71.8% for 2 and 5 mg kg-1, respectively. The lower F values after oral administration of DA-5018 to rats could be due to degradation of the drug in rat GI tract and/or considerable first-pass effect. After i.v., oral, and s.c. administration of DA-5018, the drug had a strong affinity to the rat tissues studied as reflected in the greater-than-unity tissue to plasma ratio. After i.v., oral, and s.c. administration of the drug, the biliary and urinary excretion of unchanged DA-5018 were negligible. There was no significant difference in the pharmacokinetics or tissue distribution of DA-5018 between single and multiple s.c. administration of the drug, 5 mg kg-1, to rats, indicating that there could be no tissue accumulation of the drug after multiple s.c. administration of the drug to rats.

The pharmacokinetics of DA-125 were compared after intravenous (i.v.) administration of the drug, 10 mg kg-1, to control male Sprague-Dawley rats (n = 9) and uranyl nitrate-induced acute renal failure (U-ARF, n = 12) rats, or male Sprague-Dawley rats fed on a 23% (control, n = 8) or a 5% (protein-calorie malnutrition, PCM, n = 9) protein diet. After i.v. administration of DA-125, almost 'constant' plasma concentrations of M1, M2, and M4 were maintained from 1-2 h to 8-10 h in all rat groups due to the continuous formation of M2 from M1 and M4 from M3. The plasma concentrations of M3 were the lowest among M1-M4 for all rat groups due to the rapid and almost complete conversion of M3 to M4 and other metabolite(s). The AUCt values of M1 (115 against 82.5 micrograms min mL-1), M2 (33.0 against 23.6 micrograms min mL-1), and M4 (26.3 against 15.1 micrograms min mL-1) were significantly higher in the U-ARF rats than in the control rats. The percentages of i.v. dose excreted in 24 h urine as M1 (under the detection limit against 0.316%), M2 (under the detection limit against 5.58%), and M4 (0.0174 against 0.719%)--expressed in terms of DA-125--were significantly lower in the U-ARF rats than in the control rats, and this could be due to the decreased kidney function in the U-ARF rats. However, the percentages of i.v. dose recovered from the GI tract at 24 h as M1 (0.0532% against under the detection limit), M3 (0.0286% against under the detection limit), and M4 (0.702% against 0.305%)--expressed in terms of DA-125--were significantly greater in the U-ARF rats than in the control rats. All U-ARF rats had ascites, but the concentrations of M1 (0.0320 micrograms mL-1), M2 (0.0265 micrograms mL-1), M3 (under the detection limit), and M4 (0.032 micrograms mL-1) in the ascites from one rat were almost negligible. The plasma concentrations and most of the pharmacokinetic parameters of M1, M2, and M4 were not significantly different between the PCM rats and their control rats.

The pharmacokinetics and tissue distribution of M1-M4 were compared after intravenous (i.v.) administration of DA-125, 25 mg kg-1, to BDF1 mice (n = 5 at each sampling time) and subcutaneously implanted Lewis-lung-carcinoma-bearing BDF1 mice (n = 10 at each sampling time. The mean plasma concentrations of M1-M4 were not significantly different between the two groups of mice, and hence similar pharmacokinetic parameters for M1-M4 were obtained. The amount of M1 in the lung was significantly greater in the tumour-bearing mice than in the control mice, resulting in a greater AUAt in the tumour-bearing mice (18,600 against 8940 micrograms min g-1), and vice versa in the liver (962 against 3840 micrograms min g-1). However, the corresponding values for other tissues were comparable between the control and tumour-bearing mice. The amount of M1 was greatest in the lung for up to 2 h in the tumour-bearing mice. M2 was the predominant metabolite among M1-M4 excreted in 24 h urine by both groups of mice; 8.36 and 10.7% of the i.v. dose were excreted in 24 h urine as M2--expressed in terms of DA-125--by the control and tumour-bearing mice, respectively. The amount of M1 in the tumour mass reached a mean Cmax of 3.75 micrograms g-1 immediately after i.v. administration of DA-125 to the tumour-bearing mice, then declined very slowly to an amount that remained almost constant for up to 24 h. This suggested that M1 has high affinity for the subcutaneously implanted Lewis lung carcinoma. The antitumour activity, such as the increase in life span (ILS) and tumour growth inhibition (TGI) of DA-125, 6-48 mg kg-1, and adriamycin (ADM), 3-18 mg kg-1, were also compared in subcutaneously implanted Lewis-lung-carcinoma-bearing BDF1 mice after four weekly i.v. administration of the drugs on days 1,8,15, and 22 following tumour implantation. More than three out of six mice survived as tumour-free for longer than 70 d at a DA-125 dose range of 6-24 mg kg-1, but there were no tumour-free mice at any dose of ADM. Assuming ILS values higher than 30% to be effective, DA-125 doses ranging from 6 to 24 mg kg-1 were effective in increasing the life span, which ADM does only within the dose range of 6-12 mg kg-1.

Background and objective Inhaled corticosteroids are used to treat COPD and asthma. An association between sequence variants in the corticotrophin-releasing hormone receptor 1 (CRHR1) gene and improved lung function in asthmatics treated with inhaled corticosteroids was reported recently. This study investigated the association between the change in lung function in response to inhaled corticosteroids and single-nucleotide CRHR1 polymorphisms in patients with COPD. Methods COPD patients (n = 87) with a positive smoking history were recruited from the pulmonary clinics of 11 hospitals in Korea. Patients were treated with fluticasone propionate and salmeterol for 12 weeks and lung function was measured at baseline and after the 12-week treatment. Eighty-four of the 87 subjects were successfully genotyped. Results Seventy-one patients with the wild-type GG genotype and 13 patients with the heterozygous GT genotype in rs242 941 were evaluated. After 12-week treatment, the change in FEV(1) was significantly higher in patients with wild-type GG genotype (6.0 +/- 0.8% of predicted FEV(1)) than in GT heterozygotes (-0.8 +/- 1.8, P = 0.003). Conclusions Improved FEV(1) following inhaled corticosteroid and a long-acting beta2-agonist was associated with CRHR1 genetic polymorphism in patients with COPD.

Background and objective: A new interpretative strategy for pulmonary function tests (PFT) has been proposed by the American Thoracic Society/European Respiratory Society (ATS/ERS) Task Force. To assess the accuracy of this strategy, clinical diagnosis was compared with the PFT interpretation in patients showing concomitant decreases in FEV1 and FVC. Methods: A retrospective study was conducted of 681 patients with normal FEV1/FVC and low FVC who underwent lung volume measurements and spirometry on the same date between July and November 2005 at Asan Medical Center, Seoul, Korea. Patients were clinically diagnosed by the consensus decision of two respiratory physicians, and the kappa coefficient was calculated to compare the clinical diagnosis with the PFT interpretation using the ATS/ERS strategy. Results: The PFT interpretation showed an obstructive pattern in 205 patients and a restrictive pattern in 476. Of the 205 patients with an obstructive pattern on PFT, 44 were clinically diagnosed with obstructive, 97 with restrictive and 17 with mixed disease, whereas 47 patients had no disease. Of the 476 patients with a restrictive pattern on PFT, 11 were clinically diagnosed with obstructive, 369 with restrictive and 60 with mixed disease, whereas 36 patients had no disease. The kappa coefficient was 0.35 (95% confidence interval: 0.26–0.44; P

OBJECTIVES Osteopontin (OPN) is a secreted glycoprotein, frequently associated with various tumors. We investigated the usefulness of plasma OPN level as a biomarker for hepatocellular carcinoma (HCC). METHODS We determined plasma levels of OPN, alpha-fetoprotein (AFP), and prothrombin induced by vitamin K absence II (PIVKA II) in a group of 62 HCC patients, in 60 patients with chronic liver diseases, and in 60 healthy control individuals using a standardized ELISA kit. To determine the source of elevated plasma level of OPN, immunohistochemical analysis of 285 HCC samples on tissue microarray was performed. RESULTS Plasma OPN levels in the HCC patients (median 954 ng/mL, range 168-5,742) were significantly higher (p-value < 0.001) than those patients with chronic liver diseases (381 ng/mL, 29-1,688) or of a healthy control group (155 ng/mL, 10-766). Within the HCC patient group, plasma OPN level increased significantly with advancing degree of Child-Pugh class and of tumor stage. Diagnostic sensitivity and specificity of OPN for HCC was 87% and 82%, respectively (cut-off value: 617.6 ng/mL). OPN had a greater area under curve value (0.898) than AFP (0.745) or PIVKA II (0.578), suggesting superior diagnostic accuracy of OPN. Immunohistochemistry of 285 samples of HCC showed that OPN was expressed in 92 of 285 tumors (32.3%). OPN expression was found in the malignant hepatocytes and cancer-infiltrating macrophages, not in the noncancerous hepatocytes or Kupffer cells. CONCLUSIONS These data propose elevated plasma OPN levels as a potential biomarker for HCC.

Alveolar hemorrhage and pulmonary edema induced by mechanical ventilation are partly dependent on cardiac output. Because cardiac output is low during hypothermia, we hypothesized that hypothermia may protect against these vascular manifestations of ventilator-induced lung injury. Twenty-seven Sprague-Dawley rats were assigned to either normothermia (37 +/- 1 degrees C)-injurious ventilation (NT; n = 10), hypothermia (27 +/- 1 degrees C)- injurious ventilation (HT; n = 10), or nonventilated control ( n = 7). The two ventilated groups were subjected to injurious ventilation of peak airway pressure 30 cm H(2)O with zero end-expiratory pressure for 20 min. Compared with the NT group, the hemorrhage/congestion score of the lung (11.2 +/- 1.5 vs. 4.7 +/- 1.6; p0.001) and the ratio of wet/dry lung weight (6.1 +/- 0.8 vs. 5.0 +/- 0.1; p = 0.046) of the HT group were lower. Compared with the NT group, protein concentration (3,471 +/- 1,985 micro g/ml vs. 1,374 +/- 726 micro g/ml; p = 0.003) and lactate dehydrogenase level (0.43 +/- 0.22 U/ml vs. 0.18 +/- 0.1 U/ml; p = 0.046) in bronchoalveolar lavage fluid of the HT group were lower. Whereas pressure-volume curve was shifted to the right in the NT group after injurious ventilation, it was not shifted in the HT group. In conclusion, hypothermia in rats attenuated the degrees of vascular manifestations and alveolar epithelial injuries induced by injurious ventilation, and preserved the mechanical properties of the lung.

To devise a new form of sigh ("extended sigh") capable of providing a sufficient recruiting pressure x time, and to test it as a recruitment maneuver in patients with acute respiratory distress syndrome.Prospective uncontrolled clinical trial.Medical intensive care unit of a university-affiliated hospital.Twenty consecutive patients diagnosed with acute respiratory distress syndrome (18 men, 2 women, age 59 +/- 10 yrs).From baseline settings of tidal volume (Vt) 8 mL/kg and positive end-expiratory pressure (PEEP) 10 cm H2O on volume control mode with the high pressure limit at 40 cm H2O, the Vt-PEEP values were changed to 6-15, 4-20, and 2-25, each step being 30 secs (inflation phase). After Vt-PEEP 2-25, the mode was switched to continuous positive airway pressure of 30 cm H2O for a duration of 30 secs (pause), after which the baseline setting was resumed following the reverse sequence of inflation (deflation phase). This extended sigh was performed twice with 1 min of baseline ventilation between.Airway pressures and hemodynamic parameters were traced at each step during the extended sigh. Arterial blood gases and physiologic parameters were determined before the extended sigh (pre-extended sigh), at 5 mins after two extended sighs (post-extended sigh), and then every 15 mins for 1 hr. In our average patient, the recruiting pressure x time of the inflation phase was estimated to be 32.8-35.4 cm H2O x 90 secs. Compared with the inflation phase, inspiratory pause pressure of the deflation phase was lower at Vt-PEEP 6-15 (28.9 +/- 2.7 cm H2O vs. 27.3 +/- 2.8 cm H2O) and 4-20 (31.8 +/- 2.9 cm H2O vs. 31.1 +/- 2.9 cm H2O; both p.05). Compared with pre-extended sigh, Pao2 (81.5 +/- 15.3 mm Hg vs. 104.8 +/- 25.0 mm Hg; p.001) and static respiratory compliance both increased post-extended sigh (27.9 +/- 7.9 mL/cm H2O vs. 30.2 +/- 9.7 mL/cm H2O; p =.009). Improvement in these parameters was sustained above pre-extended sigh for the duration of the study. Major hemodynamic or respiratory complications were not noted during the study.We present a new form of sigh (i.e., extended sigh) capable of achieving an augmented recruiting pressure x time through a prolonged inflation on a gradually increased end-expiratory pressure. In view of the sustained effect and absence of major complications in our patients, extended sigh could be a useful recruitment maneuver in acute respiratory distress syndrome.

Despite increasing knowledge about partial liquid ventilation (PLV), the optimal dose of perfluorocarbon (PFC) is not yet established. Because there exist normal regions in the lung with ARDS and because PLV in the normal lung results in worsened gas exchange, we postulated that the optimal dose of PFC for PLV may be less than the functional residual capacity (FRC) dose in the lung with limited disease.Animal study at the Asan Institute for Life Sciences, Seoul, Korea.Twelve rabbits in which dependent lung-dominant lung injury was created by a modified saline solution lavage.PLV performed at six different doses of perfluorodecalin in sequence (3, 6, 9, 12, 15, and 18 mL/kg every 15 min).Our modified saline solution lavage induced atelectasis and hemorrhage confined to the dependent lung with severe hypoxia (PaO(2)/fraction of inspired oxygen = 37 +/- 6 mm Hg). Peak airway pressure (Ppeak) and inspiratory pause pressure (Ppause) with PLV were lower at doses of 3 to 15 mL/kg (all p0.05), but not different at a dose of 18 mL/kg, when compared with gas ventilation. Ppeak increased at doses of 12, 15, and 18 mL/kg, when each was compared with the preceding PFC dose. At increasing PFC doses, the change in the elastic component of airway pressure (Ppause after minus Ppause before) was negative until the dose of 9 mL/kg, but was positive at doses of 12 mL/kg and above. The change in the resistive component ([Ppeak minus Ppause] after minus [Ppeak minus Ppause] before) was negative until the dose of 6 mL/kg, but was positive at the doseor = 9 mL/kg.Respiratory mechanics during PLV for dependent lung-dominant lung injury were optimal at a PFC dose less than the FRC.