2.Systematic Review and Meta-Analysis of Pulmonary Hypertension Specific Therapy for Exercise Capacity in Chronic Obstructive Pulmonary Disease.
Jinkyeong PARK ; Ju Hee SONG ; Dong Ah PARK ; Jae Seoung LEE ; Sang Do LEE ; Yeon Mok OH
Journal of Korean Medical Science 2013;28(8):1200-1206
		                        		
		                        			
		                        			Some patients with chronic obstructive pulmonary disease (COPD) have pulmonary hypertension (PH) that adversely affects survival. We performed a systematic review and meta-analysis to assess whether PH-specific therapies have an effect for stable COPD. Data sources were Medline, EMBASE, Cochrane Central Register of Controlled Trials, Korea med and references from relevant publications. Randomized prospective trials that compared PH specific therapy in COPD for more than 6 weeks with placebo were included. The outcomes were the exercise capacity and adverse events. Four randomized controlled trials involving 109 subjects were included in the analysis. Two trials involved bosentan, one sildenafil and one beraprost. The studies varied in duration of treatment from 3 to 18 months. In a pooled analysis of four trials, exercise-capacity was not significantly improved with PH-specific treatment for COPD (risk ratio, -5.1; 95% CI, -13.0 to 2.8). COPD with overt PH significantly improved the exercise capacity (mean difference, 111.6; 95% CI, 63.3 to 159.9) but COPD with PH unknown did not (mean difference, 26.6; 95% CI, -24.3 to 77.5). There was no significant difference in hypoxemia (mean difference, 2.6; 95% CI, -3.7 to 8.8). PH specific treatments have a significant effect in improving exercise capacity in COPD with overt PH.
		                        		
		                        		
		                        		
		                        			Anoxia
		                        			;
		                        		
		                        			Antihypertensive Agents/adverse effects/*therapeutic use
		                        			;
		                        		
		                        			Clinical Trials as Topic
		                        			;
		                        		
		                        			Databases, Factual
		                        			;
		                        		
		                        			Epoprostenol/adverse effects/analogs & derivatives/therapeutic use
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Hypertension, Pulmonary/complications/*drug therapy
		                        			;
		                        		
		                        			Piperazines/adverse effects/therapeutic use
		                        			;
		                        		
		                        			Pulmonary Disease, Chronic Obstructive/*etiology
		                        			;
		                        		
		                        			Purines/adverse effects/therapeutic use
		                        			;
		                        		
		                        			Questionnaires
		                        			;
		                        		
		                        			Risk Factors
		                        			;
		                        		
		                        			Sulfonamides/adverse effects/therapeutic use
		                        			;
		                        		
		                        			Sulfones/adverse effects/therapeutic use
		                        			
		                        		
		                        	
3.Phosphodiesterase Inhibitor Improves Renal Tubulointerstitial Hypoxia of the Diabetic Rat Kidney.
Hui Kyoung SUN ; Yun Mi LEE ; Kum Hyun HAN ; Han Seong KIM ; Seon Ho AHN ; Sang Youb HAN
The Korean Journal of Internal Medicine 2012;27(2):163-170
		                        		
		                        			
		                        			BACKGROUND/AIMS: Renal hypoxia is involved in the pathogenesis of diabetic nephropathy. Pentoxifyllin (PTX), a nonselective phosphodiesterase inhibitor, is used to attenuate peripheral vascular diseases. To determine whether PTX can improve renal hypoxia, we investigated its effect in the streptozocin (STZ)-induced diabetic kidney. METHODS: PTX (40 mg/kg, PO) was administered to STZ-induced diabetic rats for 8 weeks. To determine tissue hypoxia, we examined hypoxic inducible factor-1alpha (HIF-1alpha), heme oxygenase-1 (HO-1), vascular endothelial growth factor (VEGF), and glucose transporter-1 (GLUT-1) levels. We also tested the effect of PTX on HIF-1alpha in renal tubule cells. RESULTS: PTX reduced the increased protein creatinine ratio in diabetic rats at 8 weeks. HIF-1alpha, VEGF, and GLUT-1 mRNA expression increased significantly, and the expression of HO-1 also tended to increase in diabetic rats. PTX significantly decreased mRNA expression of HIF-1alpha and VEGF at 4 and 8 weeks, and decreased HO-1 and GLUT-1 at 4 weeks. The expression of HIF-1alpha protein was significantly increased at 4 and 8 weeks in tubules in the diabetic rat kidney. PTX tended to decrease HIF-1alpha protein expression at 8 weeks. To examine whether PTX had a direct effect on renal tubules, normal rat kidney cells were stimulated with CoCl2 (100 microM), which enhanced HIF-1alpha mRNA and protein levels under low glucose conditions (5.5 mM). Their expressions were similar even after high glucose (30 mM) treatment. PTX had no effect on HIF-1alpha expression. CONCLUSIONS: PTX attenuates tubular hypoxia in the diabetic kidney.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Anoxia/*drug therapy/enzymology/etiology/genetics
		                        			;
		                        		
		                        			Cell Line
		                        			;
		                        		
		                        			Cobalt/pharmacology
		                        			;
		                        		
		                        			Diabetes Mellitus, Experimental/*complications
		                        			;
		                        		
		                        			Diabetic Nephropathies/*drug therapy/enzymology/etiology/genetics
		                        			;
		                        		
		                        			Disease Models, Animal
		                        			;
		                        		
		                        			Gene Expression Regulation/drug effects
		                        			;
		                        		
		                        			Glucose/metabolism
		                        			;
		                        		
		                        			Glucose Transporter Type 1/genetics
		                        			;
		                        		
		                        			Heme Oxygenase (Decyclizing)/genetics/metabolism
		                        			;
		                        		
		                        			Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism
		                        			;
		                        		
		                        			Kidney Tubules/*drug effects/enzymology
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Pentoxifylline/*pharmacology
		                        			;
		                        		
		                        			Phosphodiesterase Inhibitors/*pharmacology
		                        			;
		                        		
		                        			RNA, Messenger/metabolism
		                        			;
		                        		
		                        			Rats
		                        			;
		                        		
		                        			Rats, Sprague-Dawley
		                        			;
		                        		
		                        			Streptozocin
		                        			;
		                        		
		                        			Time Factors
		                        			;
		                        		
		                        			Vascular Endothelial Growth Factor A/genetics
		                        			
		                        		
		                        	
5.Microenvironments and Cellular Proliferation Affected by Oxygen Concentration in Non-Small Cell Lung Cancer Cell Line.
Jong Wook SHIN ; Eun Ju JEON ; Hee Won KWAK ; Ju Han SONG ; Young Woo LEE ; Jae Woo JEONG ; Jae Cheol CHOI ; Jae Yeol KIM ; In Won PARK ; Byoung Whui CHOI
Tuberculosis and Respiratory Diseases 2007;63(3):242-250
		                        		
		                        			
		                        			BACKGROUND: Abnormal angiogenesis can induce hypoxia within a highly proliferating tumor mass, and these hypoxic conditions can in turn create clinical problems, such as resistance to chemotherapy. However, the mechanism by which hypoxia induces these changes has not yet been determined. Therefore, this study was conducted to determine how hypoxia induces changes in cell viability and extracellular microenvironments in an in vitro culture system using non-small cell lung cancer cells. METHODS: The non-small cell lung cancer cell line, A549 was cultured in DMEM or RPMI-1640 media that contained fetal bovine serum. A decrease in the oxygen tension of the media that contained the culture was then induced in a hypoxia microchamber using a CO2-N2 gas mixture. A gas analysis and an MTT assay were then conducted. RESULTS: (1) The decrease in oxygen tension was checked the anaerobic gas mixture for 30 min and then reoxygenation was induced by adding a 5% CO2-room air gas mixture to the chamber. (2) Purging with the anaerobic gas mixture was found to decrease the further oxygen tension of cell culture media. (3) The low oxygen tension resulted in a low pH, lactic acidosis and a decreased glucose concentration in the media. (4) The decrease in glucose concentration that was observed as a result of hypoxia was markedly different when different types of media were evaluated. (5) The decrease in oxygen tension inhibited proliferation of A549 cells. CONCLUSION: These data suggests that tumor hypoxia is associated with acidosis and hypoglycemia, which have been implicated in the development of resistance to chemotherapy and radiotherapy.
		                        		
		                        		
		                        		
		                        			Acidosis
		                        			;
		                        		
		                        			Acidosis, Lactic
		                        			;
		                        		
		                        			Anoxia
		                        			;
		                        		
		                        			Carcinoma, Non-Small-Cell Lung*
		                        			;
		                        		
		                        			Cell Culture Techniques
		                        			;
		                        		
		                        			Cell Line*
		                        			;
		                        		
		                        			Cell Proliferation*
		                        			;
		                        		
		                        			Cell Survival
		                        			;
		                        		
		                        			Drug Therapy
		                        			;
		                        		
		                        			Glucose
		                        			;
		                        		
		                        			Hydrogen-Ion Concentration
		                        			;
		                        		
		                        			Hypoglycemia
		                        			;
		                        		
		                        			Oxygen*
		                        			;
		                        		
		                        			Radiotherapy
		                        			
		                        		
		                        	
6.The Effects of Midazolam or Propofol Combined with Remifentanil Infusion for Central Venous Catheterization in Children.
Sang Hun RYU ; Jae Young KWON ; Hyeon Jeong LEE
Korean Journal of Anesthesiology 2007;52(6):669-674
		                        		
		                        			
		                        			BACKGROUND: Midazolam or propofol has been used for the procedural sedation in children. However, the combined use of remifentanil have not been widely investigated. The purpose of this study was to evaluate the effectiveness and safety of remifentanil infusion with intravenous anesthetics during the central venous catheterization in children. METHODS: After institutional review board approval and written informed consent from patients' parent, 20 children planned central venous catheterization for chemotherapy were randomly assigned into two groups. All patients were infused with remifentanil 0.1microng/kg/min. In M group, 0.3 mg/kg of midazolam bolus was injected and 0.1 mg/kg bolus were injected intermittently if the sedation was inadequate. In P group, 1.0 mg/kg of propofol bolus and 150microng/kg/min were infused. 0.5 mg/kg of propofol was given intermittently if the sedation was inadequate. Hemodynamic variables, end-tidal CO2 (EtCO2), bispectral index score (BIS) were monitored throughout the procedure. RESULTS: There were no significant differences in hemodynamic variables, sedation and recovery times. Oxygen saturation (SpO2) in P group was significantly lower than that of M group at 15 min after the start of infusion. EtCO2 in P group was significantly higher than that of M group at 10 min after the start of infusion. Hypoxemia (SpO2< 90%) were occurred in three patients of P group.  There was no significant difference in BIS among the groups. CONCLUSIONS: The combined infusion of remifentanil 0.1microng/kg/min with midazolam provided successful sedation without airway assistance during the central venous catheterization in children.
		                        		
		                        		
		                        		
		                        			Anesthetics, Intravenous
		                        			;
		                        		
		                        			Anoxia
		                        			;
		                        		
		                        			Catheterization, Central Venous*
		                        			;
		                        		
		                        			Central Venous Catheters*
		                        			;
		                        		
		                        			Child*
		                        			;
		                        		
		                        			Drug Therapy
		                        			;
		                        		
		                        			Ethics Committees, Research
		                        			;
		                        		
		                        			Hemodynamics
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Informed Consent
		                        			;
		                        		
		                        			Midazolam*
		                        			;
		                        		
		                        			Oxygen
		                        			;
		                        		
		                        			Parents
		                        			;
		                        		
		                        			Propofol*
		                        			
		                        		
		                        	
7.Two Cases of Fatal Hypoxemia after Talc Pleurodesis for Recurrent Malignant Pleural Effusion.
Shin Ae PARK ; Han Hee LEE ; Dae Jun KIM ; Byoung Yong SHIM ; So Hyang SONG ; Chi Hong KIM ; Myeong Im AHN ; Deog Gon CHO ; Kyu Do CHO ; Hoon Kyo KIM
Tuberculosis and Respiratory Diseases 2007;62(3):217-222
		                        		
		                        			
		                        			Talc pleurodesis is a safe and effective treatment for a recurrent malignant pleural effusion. However, acute hypoxemia, pulmonary edema or acute respiratory failure can develop in a small number of patients. We report 2 patients who developed fatal hypoxemia after talc pleurodesis which was necessary the control recurrent pleural effusion. The first case was an 18-year old male diagnosed with Ewing's sarcoma with bilateral lung metastases and pleural effusion. The performance status was ECOG (Eastern Cooperative Foncology Group) grade 3. Fever along with hypoxemia and leukocytosis developed 10 hours after the second talc pleurodesis on the right side for an uncontrolled pleural effusion, The patient died from respiratory failure after 13 days. The second case was a 66-year old female diagnosed with non-small cell lung cancer with a bone metastasis. Two weeks after systemic chemotherapy, she complained of dyspnea, and a pleural effusion was observed on the right side. Her performance status was ECOG grade 3. Talc pleurodesis was performed for recurrent pleural effusion, but hypoxemia developed 6 days after pleurodesis and she died from respiratory failure 10 days after pleurodesis. In conclusion, talc pleurodesis should be performed very carefully in patients with a poor performance status, in cases with repeated pleurodesis, bilateral pleural effusion, recent chemotherapy, radiotherapy and when there are parenchymal metastatic lesions present.
		                        		
		                        		
		                        		
		                        			Adolescent
		                        			;
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Anoxia*
		                        			;
		                        		
		                        			Carcinoma, Non-Small-Cell Lung
		                        			;
		                        		
		                        			Drug Therapy
		                        			;
		                        		
		                        			Dyspnea
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Fever
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Leukocytosis
		                        			;
		                        		
		                        			Lung
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Neoplasm Metastasis
		                        			;
		                        		
		                        			Pleural Effusion
		                        			;
		                        		
		                        			Pleural Effusion, Malignant*
		                        			;
		                        		
		                        			Pleurodesis*
		                        			;
		                        		
		                        			Pulmonary Edema
		                        			;
		                        		
		                        			Radiotherapy
		                        			;
		                        		
		                        			Respiratory Insufficiency
		                        			;
		                        		
		                        			Sarcoma, Ewing
		                        			;
		                        		
		                        			Talc*
		                        			
		                        		
		                        	
8.Rituximab-induced Interstitial Pneumonitis in a Young Patient: A Case Report and Review of the Literature.
Dong Mee LEE ; Sung Yong OH ; Hyun Ah YOON ; Suee LEE ; Sung Hyun KIM ; Hyuk Chan KWON ; Soo Keol LEE ; Hyo Jin KIM
Korean Journal of Hematology 2007;42(4):423-427
		                        		
		                        			
		                        			Side effects of rituximab are mild in most cases, but there have been a few cases of severe pulmonary toxicity reported in elderly patients. Here we report a case of interstitial pneumonitis following rituximab treatment in a young patient. A 35-year-old woman with diffuse large B-cell lymphoma was admitted complaining of dry cough and dyspnea without fever after the 3 treatments with rituximab-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy. Her chest CT with high-resolution CT scanning confirmed the presence of bilateral diffuse ground-glass opacities. The analysis of arterial blood gases indicated hypoxemia. The pulmonary function testing showed a restrictive pattern. There were no other findings suggesting an infection. The findings were compatible with a rituximab-induced interstitial pneumonitis. After the patient was treated with prednisolone, the symptoms resolved. Cases with rituximab-induced interstitial pneumonitis develop principally in elderly patients. However, the condition also can occur in young patients.
		                        		
		                        		
		                        		
		                        			Adult
		                        			;
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Anoxia
		                        			;
		                        		
		                        			Cough
		                        			;
		                        		
		                        			Doxorubicin
		                        			;
		                        		
		                        			Drug Therapy
		                        			;
		                        		
		                        			Dyspnea
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Fever
		                        			;
		                        		
		                        			Gases
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Lung Diseases, Interstitial*
		                        			;
		                        		
		                        			Lymphoma, B-Cell
		                        			;
		                        		
		                        			Prednisolone
		                        			;
		                        		
		                        			Respiratory Function Tests
		                        			;
		                        		
		                        			Tomography, X-Ray Computed
		                        			;
		                        		
		                        			Vincristine
		                        			;
		                        		
		                        			Rituximab
		                        			
		                        		
		                        	
9.Anesthetic Experience of Acquired Distal Tracheoesophageal Fistula: A case report.
Youn Suk SON ; Kyu Don CHUNG ; Hyun Sook CHO ; Sang Mook LEE ; Kuhn PARK ; Jong Ho LEE ; Ji Hyun CHUNG
Korean Journal of Anesthesiology 2006;50(3):346-350
		                        		
		                        			
		                        			A tracheoesophageal fistula (TEF) was detected in a woman who received chemotherapy for acute lymphoblastic leukemia. The fistula biopsy confirmed the aspergillus infection. A large fistula was located at the lateral wall of the carina involving the proximal left main bronchus, and the orifice of left main bronchus was almost completely obstructed by white mass-like plaque. Primary repair was planned using the right thoracotomy approach. We originally planned to selectively intubate the left lung with the aid of fiberoptic bronchoscope without success. Therefore, we selectively intubated the right lung. Hypoxemia developed during surgery and the level of oxygenation was improved by selectively intubating the left bronchus from the surgical field once the defect had been exposed. We review the ventilation technique and anesthetic problems encountered in patients with a large distal TEF.
		                        		
		                        		
		                        		
		                        			Anoxia
		                        			;
		                        		
		                        			Aspergillus
		                        			;
		                        		
		                        			Biopsy
		                        			;
		                        		
		                        			Bronchi
		                        			;
		                        		
		                        			Bronchoscopes
		                        			;
		                        		
		                        			Drug Therapy
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Fistula
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Lung
		                        			;
		                        		
		                        			Oxygen
		                        			;
		                        		
		                        			Precursor Cell Lymphoblastic Leukemia-Lymphoma
		                        			;
		                        		
		                        			Thoracotomy
		                        			;
		                        		
		                        			Tracheoesophageal Fistula*
		                        			;
		                        		
		                        			Ventilation
		                        			
		                        		
		                        	
10.Expression of Hypoxia Inducible Factor-1alpha in Invasive Squamous Cell Carcinoma of Uterine Cervix Treated by Radiotherapy.
Kyung Ja LEE ; Min Sun CHO ; Seung Cheol KIM ; Hae Sung MOON ; Hyesook PARK ; Shi Nae LEE ; Sun Hee SUNG ; Ki Nam SHIM ; Kyung Eun LEE ; Sung Ae JUNG ; Kwon YOO ; Hae Young PARK ; Soo Yeun PARK ; Eun Sun YOO ; Hyun Suk SUH
Korean Journal of Pathology 2005;39(5):307-312
		                        		
		                        			
		                        			BACKGROUND: Hypoxia-inducible factor-1alpha (HIF-1alpha) is an intrinsic marker of tumor hypoxia, and this is associated with reduced radiosensitivity. Furthermore, HIF-1alpha can increase a tumor's aggressiveness by promoting neoangiogenesis, cell proliferation and survival, and invasion. METHODS: The expression of HIF-1alpha was was investigated by performing immunohistochemistry on the cervical tissue specimens obtained from 57 patients who had received radiotherapy combined with or without chemotherapy for stages I-III cervical squamous cell carcinoma. The staining results were compared with anemia, the stage, the radiotherapy response and patient survival by univariate and multivariate analysis. RESULTS: In 57 patients, the expression of HIF-1alpha was seen in the tissue specimens of 46 patients (81.7%). Among them, 25 (54.3%), 14 (30.4%), and 7 (15.2%) of the patients' tissue specimens showed weak, moderate and strong expressions, respectively. Six patients had a partial response after radiotherapy. Twelve patients (21.1%) died of cervical cancer. The increased expression of HIF-1alpha was significantly associated (p<0.05) with the disease stage and anemia. There were significant positive correlations between the increased expression of HIF-1alpha and the poor response after radiotherapy and the patients' survival. CONCLUSIONS: The present result suggests that the overexpression of HIF-1alpha in the uterine cervix could be used as a prognostic indicator for the patients treated with radiotherapy.
		                        		
		                        		
		                        		
		                        			Anemia
		                        			;
		                        		
		                        			Anoxia*
		                        			;
		                        		
		                        			Carcinoma, Squamous Cell*
		                        			;
		                        		
		                        			Cell Proliferation
		                        			;
		                        		
		                        			Cervix Uteri*
		                        			;
		                        		
		                        			Drug Therapy
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Hypoxia-Inducible Factor 1
		                        			;
		                        		
		                        			Immunohistochemistry
		                        			;
		                        		
		                        			Multivariate Analysis
		                        			;
		                        		
		                        			Radiation Tolerance
		                        			;
		                        		
		                        			Radiotherapy*
		                        			;
		                        		
		                        			Uterine Cervical Neoplasms
		                        			
		                        		
		                        	
            
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