BACKGROUND: Skin grafts are required in numerous clinical procedures, such as reconstruction after skin removal and correction of contracture or scarring after severe skin loss caused by burns, accidents, and trauma. The current standard for skin defect replacement procedures is the use of autologous skin grafts. However, donor-site tissue availability remains a major obstacle for the successful replacement of skin defects and often limits this option. The aim of this study is to effectively expand full thickness skin to clinically useful size using an automated skin reactor and evaluate auto grafting efficiency of the expanded skin using Yucatan female pigs. METHODS: We developed an automated bioreactor system with the functions of real-time monitoring and remote-control, optimization of grip, and induction of skin porosity for effective tissue expansion. We evaluated the morphological, ultra-structural, and mechanical properties of the expanded skin before and after expansion using histology, immunohistochemistry, and tensile testing. We further carried out in vivo grafting study using Yucatan pigs to investigate the feasibility of this method in clinical application. RESULTS: The results showed an average expansion rate of 180%. The histological findings indicated that external expansion stimulated cellular activity in the isolated skin and resulted in successful grafting to the transplanted site. Specifically, hyperplasia did not appear at the auto-grafted site, and grafted skin appeared similar to normal skin. Furthermore, mechanical stimuli resulted in an increase in COL1A2 expression in a suitable environment. CONCLUSION: These findings provided insight on the potential of this expansion system in promoting dermal extracellular matrix synthesis in vitro. Conclusively, this newly developed smart skin bioreactor enabled effective skin expansion ex vivo and successful grafting in vivo in a pig model.
Bioreactors ; Burns ; Cicatrix ; Contracture ; Extracellular Matrix ; Female ; Hand Strength ; Humans ; Hyperplasia ; Immunohistochemistry ; In Vitro Techniques ; Methods ; Models, Animal ; Porosity ; Skin Transplantation ; Skin* ; Swine ; Tissue Expansion ; Tissue Expansion Devices ; Transplants

Proliferation activity has already been established as a prognostic marker or as a marker for anticancer drug sensitivity. In gastric cancer, however, the prognostic significance of proliferation activity is still being debated. Several studies evaluating proliferation activity using Ki-67 have shown controversial results in terms of the relationship between proliferation activity and overall survival (OS) or drug sensitivity in gastric cancer patients. Because cytoskeleton-associated protein 2 (CKAP2) staining has recently been introduced as a marker of proliferation activity, we analyzed 437 gastric cancer tissues through CKAP2 immunohistochemistry, and we evaluated the chromatin CKAP2-positive cell count (CPCC) for proliferation activity. Although the CPCC did not show any significant correlation with OS in the male, female or total number of cases, it did show a significant correlation in the T1 or T2 male patient subgroup, according to log-rank tests (P=0.001) and univariate analysis (P=0.045). Additionally, multivariate analysis with the Cox proportional hazard regression model showed a significant correlation between the CPCC and OS (P=0.039) for the co-variables of age, gender, T stage, N stage, histology, tumor location, tumor size and adjuvant chemotherapy. In male gastric cancer cell lines, faster-growing cancer cells showed higher sensitivity to cisplatin than slow-growing cells. Thus our study indicates that CPCC-measured proliferation activity demonstrates a significantly worse prognosis in T1 or T2 male gastric cancer patients. The CPCC will help to more precisely classify gastric cancer patients and to select excellent candidates for adjuvant chemotherapy, which in turn will facilitate further clinical chemotherapeutic trials.
Aged ; Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor/analysis ; Cell Proliferation ; Cisplatin/therapeutic use ; Cytoskeletal Proteins/*analysis ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Multivariate Analysis ; Prognosis ; Proportional Hazards Models ; Stomach/drug effects/*pathology ; Stomach Neoplasms/diagnosis/drug therapy/*pathology ; Survival Analysis

BACKGROUND AND OBJECTIVES: The correlation between brain natruretic peptide (BNP) level and cardiac autonomic function has been studied in type 2 diabetic patients. However, there is limited data from patients with normal systolic function. We evaluated the association between heart rate recovery (HRR) representing autonomic dysfunction and three plasma BNP levels: pre-exercise, post-exercise, and change during exercise in patients with normal systolic function. SUBJECTS AND METHODS: Subjects included 105 patients with chest pain and normal systolic function. HRR was defined as the difference between the peak heart rate and the rate measured two minutes after completion of a treadmill exercise test. We measured plasma BNP levels before exercise, 5 minutes after completion of exercise, and during exercise (absolute value of difference between pre- and post-exercise BNP levels). RESULTS: Patients with abnormal HRR values (< or =24 beats for the first 2 minutes of HRR) had lower high-density lipoprotein, lower peak heart rates, and higher pre- and post-exercise BNP levels than patients with normal HRR values. The patients with coronary artery disease (CAD) had abnormal HRR. However, no significant differences were found between the two groups in terms of history of hypertension (HTN), diabetes, and peak systolic blood pressure (SBP) and diastolic blood pressure (DBP). HRR was significantly associated with pre-exercise BNP (r=-0.36, p=0.004) and post-exercise BNP (r=-0.27, p=0.006), but not BNP changes. Further, pre-exercise BNP levels showed a greater association with HRR than post-exercise BNP levels. CONCLUSION: HRR is independently associated with pre-exercise and post-exercise BNP levels, even in patients with normal systolic function.
Blood Pressure ; Brain ; Chest Pain ; Coronary Artery Disease ; Exercise Test ; Heart ; Heart Rate ; Humans ; Hypertension ; Lipoproteins ; Plasma ; Stroke Volume ; Thorax

BACKGROUND: Microalbuminuria (MA) is independent predictor of cardiovascular disease and it cause mortality regardless of the presence of diabetes (DM) and hypertension (HTN). However, few published studies on this topic have been reported in Korea. Therefore, we investigated the MA prevalence and relationship between MA, insulin resistance and cardiovascular risk factor. METHODS: A total of 5,915 (3,053 men and 2,852 women) health screen examinees were enrolled in this study. We measured the anthropometric and biochemical parameters of the atherogenic indexes. RESULTS: The MA prevalence was 7.7% in all participants. The prevalence of MA in the men and women was 9.5% and 5.7%, respectively. Elevated levels of serum fasting glucose, serum fasting insulin, HOMA index, total cholesterols, LDL cholesterol, TG, Body Mass Index (BMI) and the systolic and diastolic blood pressure were significantly associated with MA. The results of multiple logistic regression analysis about MA showed that frequent drinking, low BMI, newly diagnosed DM and elevated levels of HOMA index and blood pressure were significantly associated with MA prevalence. Also, excluding newly diagnosed diabetic and hypertensive subjects, the MA prevalence was 5.7% (6.9% in men, 4.7% in women) and in multiple logistic regression analysis, the MA prevalence significantly increased in the individuals with pre-HTN rather than in the normotensives. CONCLUSIONS: The MA prevalence was 7.7% in all subjects. Except the newly diagnosed diabetic and hypertensive subjects, it was 5.7%. The MA prevalence was significantly increased in the individuals with pre-HTN rather than in the normotensives and MA was related with insulin resistance.
Blood Pressure ; Body Mass Index ; Cardiovascular Diseases ; Cholesterol ; Cholesterol, LDL ; Cross-Sectional Studies* ; Drinking ; Fasting ; Female ; Glucose ; Humans ; Hypertension ; Insulin ; Insulin Resistance ; Korea ; Logistic Models ; Male ; Mortality ; Prehypertension ; Prevalence* ; Risk Factors

BACKGROUND AND OBJECTIVES: Heart rate variability (HRV) illustrates the autonomic integration of the heart. Depressed HRV has been proven to be associated with an increased risk of cardiac death, whereas heart rate turbulence (HRT) is believed to reflect baroreflex sensitivity and it was recently introduced as another noninvasive tool for risk stratification. The aim of this study was to determine the relationship between the HRT and HRV parameters in Korean adults with a structurally normal heart. SUBJECTS AND METHODS: We studied 61 adults (males: 31) who showed ventricular premature complexes on 24 hour Holter recording and who were found to have normal hearts on full noninvasive investigation. We calculated the mean heart rate (RR interval), the number of VPBs, the time- and frequency-domain HRV parameters and two HRT parameters: turbulence onset (To) and turbulence slope (Ts). RESULTS: Ts showed a strong correlation with the HRV parameters (LF/HF ratio: r=0.35, p=0.006; VLF: r=0.32, p=0.013; LF: r=0.27, p=0.035; SDNN: r=0.28, p=0.029; SDANN: r=0.32, p=0.012), but To showed no significant correlation with the HRV parameters. CONCLUSION: The HRT parameters, and especially Ts, correlate strongly with the HRV parameters; therefore, Ts should be considered as a parameter that reflects the overall cardiac autonomic tone.
Adult* ; Baroreflex ; Death ; Heart Rate* ; Heart* ; Humans ; Ventricular Premature Complexes

BACKGROUND AND OBJECTIVES: Regular exercise protects us against numerous chronic diseases, and reduces the risk of cardiovascular disease. Also, C-reactive protein, a marker of inflammation, is known to be associated with the risk and prognosis of cardiovascular disease. The present study was designed to assess the effects of regular exercise on the level of high sensitive C-reactive protein (hsCRP). SUBJECTS AND METHODS: The serum level of hsCRP and the anthropometric indices of adiposity, metabolic variables, blood pressure (BP) and several cardiovascular risk factors were measured in 18445 subjects. A prospective study of 42 subjects with high baseline levels of hsCRP was conducted. After 3 months of regular aerobic exercise their hsCRP levels were rechecked and the association between regular exercise and hsCRP analyzed using a cross sectional and prospective study. RESULTS: Age, smoking, hypertension, diabetes and body mass index were found to be independent determinants of an elevated hsCRP level, but exercise was not found to be associated with a decreased hsCRP level in the cross-sectional study. In the prospective study, the mean serum hsCRP value was significantly reduced after 3 months in the exercise group (3.02+/-1.06 vs. 2.05+/-1.23 p=0.015), but not in the controls (3.03+/-1.09 vs. 2.57+/-1.11 p=0.104). However, the interval changes in hsCRP levels were not different in the exercise compared to the control group (p=0.660). CONCLUSION: These results suggest that exercise is not an independent determinant of the CRP level. Three months of regular aerobic exercise show a tendency to be associated with a reduction in the hsCRP level, but this putative effect of exercise on the hsCRP level was not significant in healthy subjects. Further larger sample, prospective cohort studies will be required to establish the effect of exercise on the hsCRP level.
Adiposity ; Blood Pressure ; Body Mass Index ; C-Reactive Protein* ; Cardiovascular Diseases ; Chronic Disease ; Cohort Studies ; Cross-Sectional Studies ; Exercise ; Hypertension ; Inflammation ; Prognosis ; Prospective Studies ; Risk Factors ; Smoke ; Smoking

BACKGROUND AND OBJECTIVES: Recent studies have implicated inflammation as playing an important role in the occurrence, persistence and recurrence of atrial fibrillation and that C-reactive protein is a useful marker of the inflammation. The purpose of this study is to evaluate the association between serum CRP levels and the risk of atrial fibrillation. SUBJECTS AND METHODS: This study was performed on 9,487 subjects (5,263 men and 4,224 women; mean age: 58.8+/-6.6 years) who underwent medical check-ups at the Health Promotion Center in Kanbuk Samsung Hospital. 9,438 normal control subjects and 49 atrial fibrillation patients were included in the study. The CRP was measured using a highly sensitive Behring Nephelometer II. RESULTS: When comparing the two groups, there were significant differences in age, gender and the presence of hypertension and cerebrovascular accident, and these are the previously known risk factors for atrial fibrillation. After adjustment was made for the clinical significant variables of atrial fibrillation, multiple regression analysis revealed that the hsCRP levels were not associated with the risk for atrial fibrillation (p=0.52). CONCLUSION: The inflammatory markers (CRP, WBC count) were not predictive of a higher risk for atrial fibrillation in the Korean population.
Adult* ; Atrial Fibrillation* ; C-Reactive Protein* ; Female ; Health Promotion ; Humans ; Hypertension ; Inflammation ; Male ; Recurrence ; Risk Factors ; Stroke

BACKGROUND AND OBJECTIVES: Apolipoprotein B (Apo-B) has been reported to be a better predictor of the coronary artery disease (CAD) than the cholesterol indexes. The aim of this study was to examine the concordance/discordance between the apolipoprotein B levels and the cholesterol indexes, and to assess the factors affecting the discordance. SUBJECTS AND METHODS: A total of 11,816 participants (6,965 men and 4,851 women) were enrolled in this study from all the individuals who participated in medical screening examinations at the health promotion center in Kangbuk Samsung Hospital from January to December 2002. All the participants had no history of coronary artery disease. We assessed the concordance between the biochemical parameters of the atherogenic indexes, and we evaluated the factors affecting the discordance. RESULTS: Despite the fact that the Apo-B and the various cholesterol indexes were highly correlated, the concordance rate was merely 47-56%. Multinomial logistic regression analysis showed the possibility of an increased risk for the group of discordance in whom Apo-B level was disproportionately higher than LDL cholesterol in the elderly, the smokers, the men and the people having a larger waist circumference, a lower total cholesterol level, a higher triglyceride level and a higher HDL-C level. CONCLUSION: The measurement of apo B, along with the measurement of the standard lipid profile, could be a great help in evaluating the CAD risk and for aiding in the treatment of dyslipidemia in the elderly, the smokers, men and the people having a larger waist circumference, a lower total cholesterol level, a higher triglyceride level and a higher HDL-C level.
Aged ; Apolipoproteins B ; Apolipoproteins* ; Cholesterol* ; Cholesterol, LDL ; Coronary Artery Disease ; Dyslipidemias ; Health Promotion ; Humans ; Logistic Models ; Male ; Mass Screening ; Triglycerides ; Waist Circumference

BACKGROUND AND OBJECTIVES: Several studies have reported that Brain Natriuretic Peptide (BNP) were increased in patients with chronic atrial fibrillation (AF). The objective of this study was to assess the factors influencing plasma BNP levels in patients with chronic AF and preserved left ventricular (LV) systolic function. SUBJECTS AND METHODS: Transthoracic echocardiography was performed in 55 patients (25 men, 30 women; mean age 66.6+/-11.5 years) with chronic AF. At the same time, plasma BNP was measured with a Triage(r) kit (Biosite, San Diego, California). RESULTS: Women, long duration of AF and hypertension were more prevalent in the highest quartile group of BNP levels than in the lowest quartile group of BNP levels. Significant correlations were observed between plasma BNP levels and the following: mitral E velocity (r=0.339), mitral annular E'-velocity (r=-0.396), ratio of mitral E-velocity and mitral annular E' velocity (r=0.473), left atrium (LA) size (r=0.648), LA volume index (r=0.744), right atrium (RA) volume index (r=0.554), maximal velocity (Vmax) of mitral regurgitation (MR) (r=0.444), tricuspid regurgitation (TR) Vmax (r=0.544), MR grade (r=0.431), TR grade (r=0.427) and LV mass index (r=0.570). In stepwise multiple linear regression analysis, LA volume index (beta=0.299, p=0.014), LV mass index (beta=0.404, p<0.001) and duration of AF (beta=0.488, p<0.001) independently predicted plasma BNP levels in this study subjects. The patients with increased LA volume index exhibited longer duration of AF, larger RA volume index and LV mass index, higher MR Vmax, TR Vmax, MR and TR grade and plasma BNP level. CONCLUSION: LA volume index, LV mass index and duration of AF were independent predictors of plama BNP level in patients with chronic AF and preserved LV systolic function.
Atrial Fibrillation* ; Diastole ; Echocardiography ; Female ; Heart Atria ; Humans ; Hypertension ; Linear Models ; Male ; Mitral Valve Insufficiency ; Natriuretic Peptide, Brain ; Plasma* ; Tricuspid Valve Insufficiency

BACKGROUND AND OBJECTIVES: There is a seasonal variation in the incidence of diabetes mellitus and cardiovascular disease. Insulin resistance is important in the development of both non-insulin dependent diabetes mellitus (Type II DM) and cardiovascular disease. Hyperinsulinemia, induced by an insulin resistant state, causes the development of a chronic inflammatory response in vascular structures, which is one of the main causes of cardiovascular disease. There have been several studies on seasonal variation in insulin resistance. Therefore, seasonal variation in insulin resistance were investigated to discover if any relationship existed. SUBJECTS AND METHODS: Korean people examined at a health care center were included. The subjects were divided into four groups, according to the season, and a homeostasis model assessment index (HOMA) calculated, as an indicator of insulin resistance, and compared between the groups. RESULTS: Using the homeostasis model assessment, the highest insulin resistance was observed during winter. Also, the body mass index and waist-hip ratio were highest during winter. CONCLUSION: Compensating for other metabolic factors (age, gender, body mass index, waist-hip ratio and season), insulin resistance was still found to be higher during winter. Seasonal variation in insulin resistance can be associated with the incidence of DM or cardiovascular disease. Therefore, a prospective study will be needed.
Body Mass Index ; Cardiovascular Diseases ; Delivery of Health Care ; Diabetes Mellitus ; Homeostasis ; Hyperinsulinism ; Incidence ; Insulin Resistance* ; Insulin* ; Seasons* ; Waist-Hip Ratio