BACKGROUND AND OBJECTIVES: Marfan syndrome is an autosomal dominant heritable disease of connective tissue which is characterized by cardinal features mainly in the cardiovascular, ocular and skeletal systems. Aneurysms or dissections of the aorta are the major cardiovascular complications of the disorder causing early mortality. Mutations in the fibrillin-1 (FBN1) gene on chromosome 15q21.1 have been found to be major causes of Marfan syndrome. The purpose of this study was to characterize the molecular defect in Korean Marfan patients, thus contributing to the effort of correlating the genotype with the phenotype. SUBJECTS AND METHODS: We screened all 65 exons of the FBN1 gene in 14 subjects diagnosed as Marfan syndrome by the method of single strand conformation polymorphism-heteroduplex analysis. RESULTS: We found mutations in only 10 among 14 patients. This study identified 8 novel mutations and 2 previously reported mutations in 14 Korean Marfan patients. Two cases were nonsense mutations and 8 were missense mutations, including 3 frameshift. Seven cases of the mutations occurred in one of the 43 calcium binding epidermal growth factor-like domains within an FBN1 gene. Mutations in Marfan patients occurred variably over the whole field of this FBN1 gene. CONCLUSION: Our results will contribute to the establishment of a database of Korean Marfan patients. Extending this study and using the database will help early detection of the disease and prevention of complications.
Aneurysm ; Aorta ; Calcium ; Codon, Nonsense ; Connective Tissue ; Exons ; Genotype ; Humans ; Marfan Syndrome* ; Mortality ; Mutation, Missense ; Phenotype

PURPOSE: Tumor markers are often used to monitor the response to therapy and to detect recurrences in patients with resected breast cancer. Here we evaluated the prognostic value of the preoperative serum concentrations of tumor markers in patients with breast cancer. METHODS: The preoperative serum concentrations of tumor markers (CEA, CA15-3 and TPS) were measured in 670 patients who were treated via potentially curative surgical resection for breast cancer from 2001 to 2004. We investigated the association of the serum concentrations of tumor markers with the disease-free survival and overall survival at the time of the primary diagnosis in relation to the established prognostic factors such as tumor size, lymph node status, hormonal receptor status, age and menopausal status. RESULTS: The established prognostic factors and the elevated preoperative serum tumor marker values were correlated with disease-free survival (CEA: P=0.014, CA15-3: P=0.002 and TPS: P<0.001) and overall survival (CEA: P=0.045, CA15-3: P=0.002 and TPS: P<0.001) on univariate analysis. On multivariate analysis, tumor size, lymph node status, hormone receptor status and TPS (P=0.03) were independent prognostic factors for recurrence and the lymph node status, hormone receptor status and TPS serum level (P<0.001) were independent prognostic factors for overall survival. CONCLUSION: The preoperative serum concentrations of tumor makers (CEA, CA15-3 and TPS) are strong independent prognostic factors for recurrence and survival in patients with breast cancer. The tests for the preoperativeserum concentrations of tumor markers have convenient and reproducible advantages while the others require tumor tissue. Patients with elevated preoperative serum tumor marker values need appropriate adjuvant therapy, careful monitoring and detection of recurrences during the follow-up period.
Biomarkers, Tumor ; Breast Neoplasms* ; Breast* ; Diagnosis ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Lymph Nodes ; Multivariate Analysis ; Prognosis ; Recurrence

BACKGROUND AND OBJECTIVES: Acute aortic syndrome (AAS) is a heterogeneous group of disorders that often present with severe chest or back pain. It includes acute aortic dissection (AD), intramural hematoma (IMH), dissecting aneurysm, and penetrating aortic ulcer (PAU). The clinical picture of AAS and its prognosis have not been studied in a large number of Korean patients. Therefore, we organized a multi-center registry to identify the clinical characteristics and treatment patterns, as well as long-term outcomes in Korean patients with AAS. SUBJECTS AND METHODS: Five-hundred twenty-eight patients, who had been diagnosed with AAS, were enrolled into this registry from 10 centers. On a retrospective basis, we collected demographic, laboratory, imaging data, as well as follow-up clinical outcomes by reviewing medical records from individual centers. All the data were collected in core lab and analyzed in detail. RESULTS: The mean patient age was 60.1+/-14.5 years; the male-to-female ratio was M : F=297 : 231. The prevalent risk factors for AAS included hypertension (361, 68.4%) and diabetes (52, 11.1%). The components of AAS that are included in this study are acute AD (446, 84.5%), IMH (57, 10.7%), and PAU (11, 2.1%). By type of AAS, patients diagnosed with Stanford A were 45.6% of enrolled patients, whereas those with Stanford B were 54.4% of enrolled patients. Among nearly half of the patients were treated with medicine (55.7%) alone, whereas 40.0% underwent surgery and 4.3% underwent endovascular treatment. Overall, the in-hospital event rate was 21.2% and the in-hospital death rate was 8.1%. The mean follow-up duration was 42.8 months and there showed 22.9% of total event and 10.1% of death during this period. CONCLUSION: By organizing a multi-center registry of AAS, we could identify the characteristics of AAS in real-world Korean patients. Further, prospective study is warranted with a larger number of patients.
Aneurysm, Dissecting ; Aortic Diseases ; Back Pain ; Follow-Up Studies ; Hematoma ; Humans ; Hypertension ; Medical Records ; Population Characteristics ; Prognosis ; Pyridines ; Retrospective Studies ; Risk Factors ; Thiazoles ; Thorax ; Ulcer

PURPOSE: Thiazolidinediones (TZDs) are known to inhibit the proliferation of vascular smooth muscle cell (VSMC) by increasing the activity of p27(Kip1) and retinoblastoma protein (RB). However, the upstream signaling mechanisms associated with this pathway have not been elucidated. The Akt-mTOR-P70S6 kinase pathway is the central regulator of cell growth and proliferation, and increases cell proliferation by inhibiting the activities of p27(Kip1) and retinoblastoma protein (RB). Therefore, we hypothesized in this study that rosiglitazone inhibits VSMC proliferation through the inhibition of the Akt-TOR-P70S6K signaling pathway. MATERIALS and METHODS: Rat aortic smooth muscle cells (RAoSMCs) were treated with 10microM of rosiglitazone 24 hours before the addition of insulin as a mitogenic stimulus. Western blot analysis was performed to determine the inhibitory effect of rosiglitazone treatment on the Akt-mTOR-P70S6K signaling pathway. Carotid balloon injury was also performed in Otsuka Long-Evans Tokushima Fatty (OLETF) diabetic rats that were pretreated with 3 mg/kg of rosiglitazone. RESULTS: Western blot analysis demonstrated significant inhibition of activation of p-Akt, p-m-TOR, and p-p70S6K in cells treated with rosiglitazone. The inhibition of the activation of the p-mTOR-p-p70S6K pathway seemed to be mediated by both the upstream PI3K pathway and MEK-ERK complex. CONCLUSION: The inhibitory effect of rosiglitazone on RAoSMC proliferation in vitro and in vivo is mediated by the inhibition of the Akt-mTOR-P70S6K pathway.
Animals ; Cell Proliferation/drug effects ; Cells, Cultured ; Cytoprotection/drug effects ; Enzyme Activation/drug effects ; Insulin/*pharmacology ; Male ; Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors/metabolism ; Muscle, Smooth, Vascular/drug effects/*metabolism ; Myocytes, Smooth Muscle/drug effects/*metabolism ; Phosphorylation ; Protein Kinase Inhibitors/pharmacology ; Protein Kinases/*metabolism ; Proto-Oncogene Proteins c-akt/antagonists & inhibitors/*metabolism ; Rats ; Ribosomal Protein S6 Kinases, 70-kDa/*metabolism ; Signal Transduction/drug effects ; Thiazolidinediones/*pharmacology

BACKGROUND AND OBJECTIVES: Adiponectin is known for its anti-inflammatory and anti-atherogenic effects. The purpose of this study is to characterize the relationships among serum adiponectin, essential hypertension (EH), left ventricular mass index (LVMI), and LV diastolic function. SUBJECTS AND METHODS: Serum adiponectin by RIA and body mass index were measured in 275 patients (M: F=137: 138). We calculated LVMI, E/A ratio, deceleration time (DT), and isovolumetric relaxation time (IVRT) by using echocardiograms. RESULTS: The serum adiponectin level of the hypertensive group was significantly lower than that of the non-hypertensive group (9.9+/-9.8 ug/mL vs. 12.9+/-9.5 ug/mL, p<0.05). Plasma adiponectin was negatively correlated with LVMI (r=-0.329, p<0.001), BMI (r=-0.290, p<0.001), and IVRT (r=-0.485, p<0.05), but was positively correlated with E/A (r=+0.359, p<0.001). CONCLUSION: These results suggest that a decrease in serum adiponectin is associated with an increase in blood pressure and BMI, progress of LVH, and decrease in LV diastolic function.
Adiponectin* ; Blood Pressure ; Body Mass Index ; Deceleration ; Humans ; Hypertension* ; Hypertrophy, Left Ventricular ; Plasma ; Relaxation

Acute myocardial infarction (AMI) is a fatal manifestation of ischemic heart disease and remains a major public health concern worldwide despite advances in its diagnosis and management. The characteristics of patients with AMI, as well as its disease patterns,have gradually changed over time in Korea, and the outcomes of revascularization have improved dramatically. Several characteristics associated with the revascularization of Korean patients differ from those of patients in other countries. The sophisticated state of AMI revascularization in Korea has led to the need for a Korean expert consensus. The Task Force on Expert Consensus Document of the Korean Society of Myocardial Infarction has comprehensively reviewed the outcomes of large clinical trials and current practical guidelines, as well as studies on Korean patients with AMI. Based on these comprehensive reviews, the members of the task force summarize the major guidelines and recent publications, and propose an expert consensus for revascularization in patients with AMI.

Acute myocardial infarction (AMI) is a fatal manifestation of ischemic heart disease and remains a major public health concern worldwide despite advances in its diagnosis and management. The characteristics of patients with AMI, as well as its disease patterns,have gradually changed over time in Korea, and the outcomes of revascularization have improved dramatically. Several characteristics associated with the revascularization of Korean patients differ from those of patients in other countries. The sophisticated state of AMI revascularization in Korea has led to the need for a Korean expert consensus. The Task Force on Expert Consensus Document of the Korean Society of Myocardial Infarction has comprehensively reviewed the outcomes of large clinical trials and current practical guidelines, as well as studies on Korean patients with AMI. Based on these comprehensive reviews, the members of the task force summarize the major guidelines and recent publications, and propose an expert consensus for revascularization in patients with AMI.

Background and Objectives: Prior studies have shown that stroke patients treated with percutaneous left atrial appendage occlusion (LAAO) for non-valvular atrial fibrillation (NVAF) experience better outcomes than similar patients treated with warfarin. We investigated the impact of percutaneous left atrial appendage closure on post-stroke neurological outcomes in NVAF patients, compared with non-vitamin K antagonist oral anticoagulant (NOAC) therapy. Methods: Medical records for 1,427 patients in multiple registries and for 1,792 consecutive patients at 6 Korean hospitals were reviewed with respect to LAAO or NOAC treatment.Stroke severity in patients who experienced ischemic stroke or transient ischemic attack after either treatment was assessed with modified Rankin Scale (mRS) scoring at hospital discharge and at 3 and 12 months post-stroke. Results: mRS scores were significantly lower in LAAO patients at 3 (p<0.01) and 12 months (p<0.01) post-stroke, despite no significant differences in scores before the ischemic cerebrovascular event (p=0.22). The occurrences of disabling ischemic stroke in the LAAO and NOAC groups were 36.7% and 44.2% at discharge (p=0.47), 23.3% and 44.2% at 3 months post-stroke (p=0.04), and 13.3% and 43.0% at 12 months post-stroke (p=0.01), respectively.Recovery rates for disabling ischemic stroke at discharge to 12 months post-stroke were significantly higher for LAAO patients (50.0%) than for NOAC patients (5.6%) (p<0.01). Conclusions Percutaneous LAAO was associated with more favorable neurological outcomes after ischemic cerebrovascular event than NOAC treatment.

Background and Objectives: Prior studies have shown that stroke patients treated with percutaneous left atrial appendage occlusion (LAAO) for non-valvular atrial fibrillation (NVAF) experience better outcomes than similar patients treated with warfarin. We investigated the impact of percutaneous left atrial appendage closure on post-stroke neurological outcomes in NVAF patients, compared with non-vitamin K antagonist oral anticoagulant (NOAC) therapy. Methods: Medical records for 1,427 patients in multiple registries and for 1,792 consecutive patients at 6 Korean hospitals were reviewed with respect to LAAO or NOAC treatment.Stroke severity in patients who experienced ischemic stroke or transient ischemic attack after either treatment was assessed with modified Rankin Scale (mRS) scoring at hospital discharge and at 3 and 12 months post-stroke. Results: mRS scores were significantly lower in LAAO patients at 3 (p<0.01) and 12 months (p<0.01) post-stroke, despite no significant differences in scores before the ischemic cerebrovascular event (p=0.22). The occurrences of disabling ischemic stroke in the LAAO and NOAC groups were 36.7% and 44.2% at discharge (p=0.47), 23.3% and 44.2% at 3 months post-stroke (p=0.04), and 13.3% and 43.0% at 12 months post-stroke (p=0.01), respectively.Recovery rates for disabling ischemic stroke at discharge to 12 months post-stroke were significantly higher for LAAO patients (50.0%) than for NOAC patients (5.6%) (p<0.01). Conclusions Percutaneous LAAO was associated with more favorable neurological outcomes after ischemic cerebrovascular event than NOAC treatment.