BACKGROUND: Through a genome-wide search using the genetic markers(RFLP genetic markers), the familial hypertrophic cardiomyopathy(FHCM) with an autosomal dominant mode of inheritance has been firstly detected to be genetically linked to chromosome 14q1. The subsequent studies have shown that the point mutations at the exons encoding for the head and head /rod junction of the cardiac beta myosin heavy chain(beta-MHC) are the most frequent type of mutation in the FHCM families genetically implicated with a linkage to beta-MHC, whereas the alpha/beta-MHC hybrid gene and a large deletion at the 3' region of beta-MHC gene were also rarely detected. With the other families genetically implicated with the chromosomes 1,11,15,16 and 18, FHCM also manifests locus heterogeneity, a phenomenon in which abnormalities at different genes are involved in different families. In addition, a korean FHCM family with 403Arg-->Gln mutation of beta-MHC gene has been previously found by an american research group. METHODS: For clinical diagnosis, echocardiography and electrocardiography were performed on the individual members of a korean FHCM family. The microsatellite markers(MYO-I,MYO-II) located in the beta-MHC gene region were amplified by PCR(polymerase chain reaction) and the polymorphism was analyzed for the possible linkage to the phenotypic expression of FHCM. Independently, the same PCR products of the exons 13 and 23 were digested with the specific restriction enzymes for the presence of the most frequently reported point mutations of beta-MHC gene (403 and 908 amino acid mutations). Single strand conformation polymorphism(SSCP) of the exon 13 and 23 of the beta-MHC gene was also analyzed of the mobility shift expected if any point mutation is present at these two exons. RESULTS: The inheritance pattern of HCM(hypertrophic cardiomyopathy) in the family is considered as autosomal dominant. In this family(KU 101), one of the microsatellite markers(MYO-II) indicated the possible cosegregation between the allele was also present in the 32-year-old brother of the proband, who reveals no clinical signs of the disease. The other microsatellite genetic marker(MYO-I) was uninformative, without giving the discriminating power to verify the linkage to beta-MHC gene. In the analysis for two common mutations of beta-MHC gene by PCR-RFLP and PCR-SSCP, no evidence was found for 403 and 908 amino acid mutations and any point mutation in the exons 13 and 23. CONCLUSIONS: Based on the linkage analysis using microsatellite genetic markers, there was a possibility that the disease could be linked to an abnormality in the beta-MHC gene of the chromosome 14q1.
Adult ; Alleles ; Cardiomyopathy, Hypertrophic, Familial* ; Diagnosis ; Echocardiography ; Electrocardiography ; Exons ; Genetic Markers ; Head ; Humans ; Inheritance Patterns ; Mass Screening* ; Microsatellite Repeats ; Point Mutation ; Polymerase Chain Reaction ; Population Characteristics ; Siblings ; Ventricular Myosins* ; Wills

BACKGROUND: Through a genome-wide search using the genetic markers(RFLP genetic markers), the familial hypertrophic cardiomyopathy(FHCM) with an autosomal dominant mode of inheritance has been firstly detected to be genetically linked to chromosome 14q1. The subsequent studies have shown that the point mutations at the exons encoding for the head and head /rod junction of the cardiac beta myosin heavy chain(beta-MHC) are the most frequent type of mutation in the FHCM families genetically implicated with a linkage to beta-MHC, whereas the alpha/beta-MHC hybrid gene and a large deletion at the 3' region of beta-MHC gene were also rarely detected. With the other families genetically implicated with the chromosomes 1,11,15,16 and 18, FHCM also manifests locus heterogeneity, a phenomenon in which abnormalities at different genes are involved in different families. In addition, a korean FHCM family with 403Arg-->Gln mutation of beta-MHC gene has been previously found by an american research group. METHODS: For clinical diagnosis, echocardiography and electrocardiography were performed on the individual members of a korean FHCM family. The microsatellite markers(MYO-I,MYO-II) located in the beta-MHC gene region were amplified by PCR(polymerase chain reaction) and the polymorphism was analyzed for the possible linkage to the phenotypic expression of FHCM. Independently, the same PCR products of the exons 13 and 23 were digested with the specific restriction enzymes for the presence of the most frequently reported point mutations of beta-MHC gene (403 and 908 amino acid mutations). Single strand conformation polymorphism(SSCP) of the exon 13 and 23 of the beta-MHC gene was also analyzed of the mobility shift expected if any point mutation is present at these two exons. RESULTS: The inheritance pattern of HCM(hypertrophic cardiomyopathy) in the family is considered as autosomal dominant. In this family(KU 101), one of the microsatellite markers(MYO-II) indicated the possible cosegregation between the allele was also present in the 32-year-old brother of the proband, who reveals no clinical signs of the disease. The other microsatellite genetic marker(MYO-I) was uninformative, without giving the discriminating power to verify the linkage to beta-MHC gene. In the analysis for two common mutations of beta-MHC gene by PCR-RFLP and PCR-SSCP, no evidence was found for 403 and 908 amino acid mutations and any point mutation in the exons 13 and 23. CONCLUSIONS: Based on the linkage analysis using microsatellite genetic markers, there was a possibility that the disease could be linked to an abnormality in the beta-MHC gene of the chromosome 14q1.
Adult ; Alleles ; Cardiomyopathy, Hypertrophic, Familial* ; Diagnosis ; Echocardiography ; Electrocardiography ; Exons ; Genetic Markers ; Head ; Humans ; Inheritance Patterns ; Mass Screening* ; Microsatellite Repeats ; Point Mutation ; Polymerase Chain Reaction ; Population Characteristics ; Siblings ; Ventricular Myosins* ; Wills

PURPOSE: To report the clinical efficacy and safety of progressive keratoconic eyes in Korean patients treated with accelerated corneal cross-linking. METHODS: This retrospective study focused on progressive keratoconic eyes in Korean patients that underwent accelerated corneal cross-linking from February 2015 to October 2015. Keratoconus was diagnosed in 45 eyes in 30 patients. After accelerated corneal cross-linking with VibeX rapid solution, best corrected visual acuity, maximum keratometry, mean keratometry, corneal thickness, corneal astigmatism, and endothelial cell count were measured at the preoperative visit and post operation 1 week, 1 month, 3 months, and 6 months. RESULTS: Best corrected visual acuity (log MAR) was 0.51 ± 0.23 at pre operation and 0.51 ± 0.26 at post operation 6 months, showing no improvement. The maximum keratometry measured with Auto K, Pentacam, and Orbscan II at pre operation was 49.11 ± 4.5 D, 48.37 ± 3.31 D, and 48.98 ± 4.88 D and changed to 49.29 ± 4.34 D, 46.99 ± 3.63 D, and 47.01 ± 3.62 D postoperatively, respectively. Only Pentacam and Orbscan II measurements showed a statistically significant decrease (p < 0.05). Corneal thickness (at the thinnest area) was measured with Pentacam and Orbscan II; pre-operative and post-operative 6 month data showed changes from 485 ± 26.27 and 479.24 ± 27.89 to 471.64 ± 27.12 and 472.52 ± 25.36, respectively. Only the Pentacam method resulted in a statistically significant decrease. Endothelial cell count was measured with confocal microscopy and showed a statistically significant difference between pre-operative 2,857 ± 390.49/mm² and post-operative 6 month 2,639.21 ± 249.92/mm². CONCLUSIONS: This 6-month follow-up study of Korean keratoconus patients who underwent accelerated corneal cross-linking indicates that the method is effective in stabilizing the progression of keratoconus, according to maximum keratometry change. With regard to endothelial cell count change, further long-term evaluation is required. Other than endothelial cell count change, this procedure is expected to show long-term safety comparable to that of conventional corneal cross-linking.
Astigmatism ; Collagen* ; Endothelial Cells ; Follow-Up Studies ; Humans ; Keratoconus* ; Methods ; Microscopy, Confocal ; Retrospective Studies ; Treatment Outcome ; Visual Acuity

Purpose: To study the risk factors for steroid-induced glaucoma patients requiring glaucoma surgery, despite being fully treated with medications and laser trabeculoplasty. Methods: The charts of 50 eyes diagnosed with steroid-induced glaucoma from January 2012 to December 2015 were reviewed retrospectively. 28 eyes required surgery and 22 eyes were successfully treated with medications and laser trabeculoplasty. The demographic information as well as ocular parameters, presence of ocular/systemic comorbidities, and past history of steroid use were evaluated to determine the risk factors associated with the need for glaucoma surgery. Results: For the 7 factors that were statistically significant by univariate regression analysis, multivariate regression analysis showed that the average retinal nerve fiber layer thickness and duration of steroid use were not statistically significant (p = 0.876 and p = 0.068, respectively), whereas age and initial intraocular pressure were only statistically significant in some of the analysis models (p = 0.040-0.278, p = 0.016-0.201, respectively). Myopia, vertical cup-to-disc ratio, and systemic comorbidities had statistically significant correlations (p = 0.019, p = 0.011-0.03, p = 0.022, respectively) with surgical decision by multivariate regression analysis. Conclusions The risk factors for requiring glaucoma surgery in steroid-induced glaucoma patients were young age, myopia, initial optic nerve damage, systemic disease (systemic lupus erythematosus, rheumatoid arthritis, and atopy), and duration of steroid use. These results may be helpful in predicting the prognosis of patients with steroid-induced glaucoma and in screening for patients who require a more aggressive treatment at the time of disease presentation.

BACKGROUND: It has been hypothesized that early atherosclerosis may be related to the pathogenesis of coronary vasospasm. This study was designed to investigate the relationship between early atherosclersosis and coronary vasospasm or vasoconstriction in response to axetylcholine utilizing intravascular ultrasonography. METHOD: Total 43 segments were analyzed from subjects who were composed of 10 patients with and 7 patients without coronary vasospasm in response to intra coronary acetylcholine infusion. Spasm segment(Sp) was defined as total or subtotal occlusion, constriction segment(C) as diameter decrease>/=10%, and normal segment(N) as diameter decrease<10% compared to baseline coronary angiogram. Atherosclerotic plaque thickness was defined as the sum of thickness of intimal leading edge and sonolucent zone. Atherosclerosis was defined as atherosclerotic plaque thickness > 0.5mm. RESULTS: The atherosclerotic plaques of spasm segments were significantly thicker than those of normal and constriction segments(spasm segments : 1.19+/-0.21mm, constrict segments : 0.58+/-0.11mm, normal segment : 0.37+/-0.11, p<0.05). Atherosclerosis was present in 90% of spasm segments. Among normal of constriction segments, atherosclerotic plaque thickness of patients with vasospasm was thicker than that of patients without vasospasm, although it was statistically insignificant(patients with vasospasm : 0.65+/-0.51mm, patients without vasospasm 0.36+/-0.39mm, p=0.07). Frequency of atherosclerosis in normal or constriction segments was significantly higher in patients with vasospasm than patients without vasospasm(patients with vasospasm 47%, patients without vasospasm : 11%, p<0.05). CONCLUSION: Atherosclerosis is present at segments of vasospasm in response to intracoronary acetylcholine. Even among normal or constriction segments, the artherosclerotic plaque thickness of patients with vasospasm was thicker than that of patients without vasospasm which may indicates that coronary vasospasm is a diffuse early atherosclerotic disease.
Acetylcholine ; Atherosclerosis ; Constriction ; Coronary Vasospasm* ; Humans ; Plaque, Atherosclerotic ; Spasm ; Ultrasonography* ; Ultrasonography, Interventional ; Vasoconstriction*

BACKGROUND AND OBJECTIVES: During coronary angioplasty, a distal embolization of the intracoronary thrombus is associated with an increased risk of myocardial infarction and mortality. Recently, distal protection devices have been tested for distal embolization with varying success. Here we report the experiences with one of the distal protection devices, Percusurge(r). SUBJECTS AND METHODS: From January 2001 to August 2001, 5 cases of a Percusurge(r) being used in patients with intracoronary thrombus were experienced during the angioplasty (male:4, female:1). Both the pre- and post-procedural clinical findings of the patients, the angiographic findings, the number of acute complications, the presence of biochemical marker such as CK-MB, and any in-hospital cardiac events were reviewed. RESULTS: Percusurge(r) was used in the right coronary artery (RCA) in 4 cases and in the saphenous vein graft in 1. The clinical diagnosis included stable angina (2 patients), non-Q wave myocardial infarction (1 patient), and Q-wave myocardial infarction (2 patients). The patients showed a TIMI 0 or 1 flow in 4 patients with a RCA lesion and TIMI 3 flow in 1 patient with a saphenous vein graft lesion. However, the TIMI 3 flow was recovered in all cases after the intervention. The CK-MB level did not show any significant changes between the pre- and post-procedure in 4 cases (11.2 +/- 3.2 U/L vs 10.2 +/- 2.1 U/L). However, one of the distal branchs was totally occluded by the distal embolization of the thrombus, and the CK-MB level increased from 2.1 U/L to 22.7 U/L. Otherwise, no procedure-related complications or major in-hospital cardiac events were observed. CONCLUSION: The use of the distal protection device, Percusurge(r), may reduce both the procedural and clinical complications during a coronary intervention in the thrombus-containing lesion. However, a large prospective study is needed to define the role of the distal protection device.
Angina, Stable ; Angioplasty ; Biomarkers ; Coronary Thrombosis ; Coronary Vessels ; Diagnosis ; Humans ; Mortality ; Myocardial Infarction ; Saphenous Vein ; Thrombosis* ; Transplants

BACKGROUND AND OBJECTIVES: This study was performed to investigate the antiproliferative effect of lovastatin on vascular smooth muscle cell, especially to determine whether lovastatin induces apoptosis in vascular smooth muscle cell and the products of mevalonate pathway can reverse the antiproliferative effect of lovastatin. METHODS AND MATERIALS: Lovastatin only and lovastatin with one of the products of mevalonate pathway such as isopentenyl adenine, farnesol, mevalonate, cholesterol were added respectively in cultured rat vascular smooth muscle cells stimulated with 10% fetal calf serum. DNA synthesis was measured by tritiated-thymidine incorporation. Cell number was determined by hemocytometric counting. Cells were Giemsa-stained to evaluate morphological changes of apoptosis. Extracted DNA from the cells treated with lovastatin was assessed by gel electrophoresis. RESULTS: 1)Lovastatin inhibited DNA synthesis and cell proliferation in a dose-dependent manner. 2)The inhibitory effects of lovastatin could be reversed almost completely by mevalonate, partially by farnesol. 3)Lovastatin-treated vascular smooth muscle cells showed typical morphological changes of apoptosis. 4)A distinct ladder of DNA bands was visualized by gel electrophoresis of the DNA from the cells treated with lovastatin. CONCLUSION: Mevalonate metabolism is essential for vascular smooth muscle cell proliferation. The antiproliferative effect of lovastatin may result from the induction of apoptosis in vascular smooth muscle cells.
Adenine ; Animals ; Apoptosis ; Cell Count ; Cell Proliferation ; Cholesterol ; DNA ; Electrophoresis ; Farnesol ; Lovastatin* ; Metabolism ; Mevalonic Acid ; Muscle, Smooth, Vascular* ; Rats

BACKGROUND AND OBJECTIVES: Neurocardiogenic syncope is believed to be caused by a transient imbalance of autonomic nervous system. Actually, there were significant differences in heart rate variability (HRV) indices during head-up tilt test between patients with neurocardiogenic syncope and normal controls. But there was no definite evidence for it during daily activity. So, we tried to evaluate HRV during daily activity with 24-hour ambulatory electrocardiography monitoring. MATERIALS AND METHODS: 27 patients with neurocardiogenic syncope or presyncope (mean age 45+/-3) and 25 normal volunteers (mean age 47+/-2) comparable for age and sex underwent 24-hour ambulatory electrocardiography. Head-up tilt test was used to diagnose neurocardiogenic syncope or presyncope in patients group. HRV was analysed over the whole 24 hours, using time and frequency domain parameters. Student's t-test was applied. ResultsThere were no significant differences in HRV measures between two groups, over 24-hour period and day-time and night-time period. But the hourly HRV measures showed a transient decrease of LF, LFnorm and LF/HF ratio in patients group compared to normal control group. CONCLUSIONS: These results indicate that patients with neurocardiogenic syncope or presyncope suffer from temporarily decreased sympathetic tone with normal parasympathetic tone. So, transient additive change of autonomic nervous tone may cause syncope or presyncope in these patients. (Korean Circulation J 2000;30 (6):716-723)
Autonomic Nervous System ; Electrocardiography, Ambulatory ; Healthy Volunteers ; Heart Rate* ; Heart* ; Humans ; Syncope* ; Syncope, Vasovagal*

BACKGROUND: It has been suggested that all components of the renin-angiotensin-aldosterone system (RAAS) are present in the vascular wall and that the vascular RAAS modulates vascular tone and vascular hypertrophy. One of the catalytic step in the RAAS cascade is the local conversion of angiotensin I to angiotensin II (Ang II) by angiotensin converting enzyme (ACE). One of the major sources of ACE in the vasculature is vascular smooth muscle cells (VSMC). Here, we provide insight into the intrinsic mechanisms by which the components of RAAS regulate gene expression of ACE in cultured smooth muscle cells of the rat and we also investigated the effects of cytokines on ACE mRNA. METHODS: RNA was extracted from the primary cultured VSMCs. We analyzed the expression levels of ACE by competitive reverse transcription-PCR using recombinant RNA as an internal standard. RESULTS: 1) ACE mRNA level was increased markedly by aldosterone in a dose- and time-dependent manner, indicating that there exists positive feedback mechanism within RAAS. 2) The induction of ACE mRNA by aldosterone was inhibited by spironolactone. 3) Aldosterone-stimulated expression of ACE was also inhibited by Ang II, which shows that Ang II acts as a negative regulator of the expression of ACE in RAAS cascade. 4) Interleukin-1beta or TNF-alpha did not induce ACE mRNA expression. 5) However, mixture of interleukin-1betaand TNF-alpha(CytoMix) significantly increased the expression of ACE. It was also shown that CytoMix increased aldosterone-stimulated ACE mRNA expression in an additative manner. CONCLUSION: These results indicate that the expression of ACE in smooth muscle cells is modulated by the components of RAAS and cytokines. The intrinsic positive and negative feedback controls of RAAS would play an important role in the pathogenesis of vascular diseases.
Aldosterone* ; Angiotensin I ; Angiotensin II ; Angiotensins* ; Animals ; Cytokines* ; Gene Expression ; Hypertrophy ; Interleukin-1beta ; Muscle, Smooth, Vascular* ; Myocytes, Smooth Muscle ; Peptidyl-Dipeptidase A* ; Rats ; Renin-Angiotensin System ; RNA ; RNA, Messenger ; Spironolactone ; Tumor Necrosis Factor-alpha* ; Vascular Diseases

BACKGROUND AND OBJECTIVES: Heart rate variability(HRV) reflects the autonomic integration of heart. There were many reports that HRV in patients with myocardial infarction or heart failure is an independent prognostic factor to predict fatal arrhythmia and sudden cardiac death. But, the role of HRV is still controversial in stable angina patients without history of myocardial infarction. In this study, we tried to compare HRV indices between stable angina patients and normal subjects. MATERIALS AND METHODS: Twenty-one stable anginal patients without history of myocardial infarction (mean age : 57 +/- 2 years) and twenty-one relatively healthy persons without history of coronary heart disease (mean age : 53 +/- 2 years) were included in the study and underwent 24-hour ambulatory ECG monitoring. In patients group, all underwent coronary angiography after 24-hour ambulatory ECG monitoring. HRV was analyzed over the whole 24 hours, using time and frequency domain parameters, according to time phases and coronary angiographic severity. RESULTS: There were no significant differences in age, sex and cardiovascular risk factors, except hypertension (p=.001) between two groups. HRV indices such as rMSSD, pNN50, LF, HF, LFnorm and HFnorm were significantly decreased (p<0.05) in patients group. But the angiographic severity of coronary arteries did not show any significant effect on the HRV indices in patients group. CONCLUSIONS: We observed significantly reduced HRV indices in patients with stable angina without history of myocardial infarction.
Angina, Stable* ; Arrhythmias, Cardiac ; Coronary Angiography ; Coronary Disease ; Coronary Vessels ; Death, Sudden, Cardiac ; Electrocardiography ; Heart Failure ; Heart Rate* ; Heart* ; Humans ; Hypertension ; Myocardial Infarction* ; Risk Factors