Surgical Trends of Shoulder Arthroplasty: Nationwide Epidemiologic Study in South Korea

Background@#The aim of this study was to determine the nationwide shoulder arthroplasty trends in South Korea based on an analysis of nationwide data acquired from the Korean Health Insurance Review and Assessment Service (HIRA). @*Methods@#We analyzed a nationwide database acquired from the HIRA that covered 2008 to 2017. International Classification of Diseases, 10th Revision (ICD-10) codes and procedure codes were used to identify patients who underwent shoulder arthroplasty, including total shoulder arthroplasty (TSA), hemiarthroplasty (HA), and revision shoulder arthroplasty. @*Results@#From 2008 to 2017, a total of 19,831 shoulder arthroplasties were performed; there were 16,162 TSAs and 3,669 hemiarthroplasties. During the 10-year study period, there was an exponential increase in the incidence of TSA (from 513 cases in 2008 to 3,583 cases in 2017), while the number of hemiarthroplasties remained steady. The most common diagnoses for TSA were rotator cuff tears (6,304 cases, 39.0%) and osteoarthritis (6,589 cases, 40.8%) for all 9 years. Osteoarthritis was the most common reason for TSA during the first 3 years (2008–2010), but rotator cuff tears ultimately surpassed osteoarthritis during the last 3 years (2015–2017). HA was performed to treat proximal humerus fracture (1,770 cases, 48.2%) and osteoarthritis (774 cases, 21.1%). In terms of hospital types, the rate of TSA in hospitals with 30–100 inpatient beds increased from 21.83% to 46.27%, while the rates of the other types of surgery decreased. A total of 430 revision surgeries were performed during the study period, and infection (152 cases, 35.3%) was the most common reason for revision surgery. @*Conclusions@#Overall, the total count and incidence of TSA, unlike HA, increased rapidly between 2008 and 2017 in South Korea. Moreover, at the end of the study period, nearly half of the TSAs were performed in small hospitals (30 to 100 beds). Rotator cuff tears were the leading cause of TSA at the end of the study period. These findings revealed an explosive increase in reverse TSA surgery.

Safety and Efficacy of Biodegradable Polymer-biolimus-eluting Stents (BP-BES) Compared with Durable Polymer-everolimus-eluting Stents (DP-EES) in Patients Undergoing Complex Percutaneous Coronary Intervention

BACKGROUND AND OBJECTIVES: There are no data comparing clinical outcomes of complex percutaneous coronary intervention (PCI) between biodegradable polymer-biolimus-eluting stents (BP-BES) and durable polymer-everolimus-eluting stents (DP-EES). We sought to evaluate the safety and efficacy of BP-BES compared with DP-EES in patients undergoing complex PCI. METHODS: Patients enrolled in the SMART-DESK registry were stratified into 2 categories based on the complexity of PCI. Complex PCI was defined as having at least one of the following features: unprotected left main lesion, ≥2 lesions treated, total stent length >40 mm, minimal stent diameter ≤2.5 mm, or bifurcation as target lesion. The primary outcome was target lesion failure (TLF), defined as a composite of cardiac death, target vessel-related myocardial infarction (TV-MI), or target lesion revascularization (TLR) at 2 years of follow-up. RESULTS: Of 1,999 patients, 1,145 (57.3%) underwent complex PCI: 521 patients were treated with BP-BES and 624 with DP-EES. In propensity-score matching analysis (481 pairs), the risks of TLF (3.8% vs. 5.2%, adjusted hazard ratio [HR], 0.578; 95% confidence interval [CI], 0.246–1.359; p=0.209), cardiac death (2.5% vs. 2.5%, adjusted HR, 0.787; 95% CI, 0.244–2.539; p=0.689), TV-MI (0.5% vs. 0.4%, adjusted HR, 1.128; 95% CI, 0.157–8.093; p=0.905), and TLR (1.1% vs. 2.9%, adjusted HR, 0.390; 95% CI, 0.139–1.095; p=0.074) did not differ between 2 stent groups after complex PCI. CONCLUSIONS: Clinical outcomes of BP-BES were comparable to those of DP-EES at 2 years after complex PCI. Our data suggest that use of BP-BES is acceptable, even for complex PCI.

Proteome Analysis of Alkylhydroxide Peroxidase-Deficient Isogenic Mutant of Helicobacter pylori 26695

In order to investigate the antioxidant effect of alkylhydroxide peroxidase (ahpC) of Helicobacter pylori (H. pylori) 26695, an ahpC-deficient mutant (H. pylori 26695 ahpC::cat) was generated. ahpC-deficient mutant was grown slowly at lower pressure of oxygen (5% oxygen) compared to the H. pylori 26695. Whole cell proteins isolated form H. pylori 26695 and H. pylori 26695 ahpC::cat were analyzed by MALDI-TOF and tandem-MS. The expression of 15 proteins, including Ppa, HypB, GrpE, Elp, RecA, GroES, Mda66, RibE, NapA, GlnA, BioB, TrxB, Tsf, FumC and Icd, was more than doubled in H. pylori 26695 ahpC::cat. Production of 10 proteins such as UreG, FabE, Adk, Pnp, OorC, AtpA, AtpD, Nqq3, Pfr, and TagD decreased below 50% in H. pylori 26695 ahpC::cat compared to the H. pylori 26695. In microarray analysis, 9 genes including sul1, amiE, frxA, fecA, hyuA, and katA increased in transcription level in H. pylori 26695 ahpC::cat compared to H. pylori 26695. A total of 24 genes, including flaB, protein kinase C inhibitor, cag16, pabC, and sabA, reduced in transcription. 27 genes, including HP0889, showed common expression changes in ahpC, katA, and sodB-deficient mutations. As a result of this study, there were not many genes whose expression was commonly changed by the deletion of each of the three major antioxidant enzymes of H. pylori. These results showed the functions and regulation of the three antioxidant enzymes were different in H. pylori.

Safety and Efficacy of Biodegradable Polymer-biolimus-eluting Stents (BP-BES) Compared with Durable Polymer-everolimus-eluting Stents (DP-EES) in Patients Undergoing Complex Percutaneous Coronary Intervention

BACKGROUND AND OBJECTIVES@#There are no data comparing clinical outcomes of complex percutaneous coronary intervention (PCI) between biodegradable polymer-biolimus-eluting stents (BP-BES) and durable polymer-everolimus-eluting stents (DP-EES). We sought to evaluate the safety and efficacy of BP-BES compared with DP-EES in patients undergoing complex PCI.@*METHODS@#Patients enrolled in the SMART-DESK registry were stratified into 2 categories based on the complexity of PCI. Complex PCI was defined as having at least one of the following features: unprotected left main lesion, ≥2 lesions treated, total stent length >40 mm, minimal stent diameter ≤2.5 mm, or bifurcation as target lesion. The primary outcome was target lesion failure (TLF), defined as a composite of cardiac death, target vessel-related myocardial infarction (TV-MI), or target lesion revascularization (TLR) at 2 years of follow-up.@*RESULTS@#Of 1,999 patients, 1,145 (57.3%) underwent complex PCI: 521 patients were treated with BP-BES and 624 with DP-EES. In propensity-score matching analysis (481 pairs), the risks of TLF (3.8% vs. 5.2%, adjusted hazard ratio [HR], 0.578; 95% confidence interval [CI], 0.246–1.359; p=0.209), cardiac death (2.5% vs. 2.5%, adjusted HR, 0.787; 95% CI, 0.244–2.539; p=0.689), TV-MI (0.5% vs. 0.4%, adjusted HR, 1.128; 95% CI, 0.157–8.093; p=0.905), and TLR (1.1% vs. 2.9%, adjusted HR, 0.390; 95% CI, 0.139–1.095; p=0.074) did not differ between 2 stent groups after complex PCI.@*CONCLUSIONS@#Clinical outcomes of BP-BES were comparable to those of DP-EES at 2 years after complex PCI. Our data suggest that use of BP-BES is acceptable, even for complex PCI.

Risk Scoring System to Assess Outcomes in Patients Treated with Contemporary Guideline-Adherent Optimal Therapies after Acute Myocardial Infarction

BACKGROUND AND OBJECTIVES: A risk prediction is needed even in the contemporary era of acute myocardial infarction (AMI). We sought to develop a risk scoring specific for patients with AMI being treated with guideline-adherent optimal therapies, including percutaneous coronary intervention and all 5 medications (aspirin, thienopyridine, β-blocker, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, and statin). METHODS: From registries, 12,174 AMI patients were evaluated. The primary outcome was 1-year all-cause death or AMI. The Korea Working Group in Myocardial Infarction (KorMI) system was compared with the Assessment of Pexelizumab in Acute Myocardial Infarction (APEX AMI), Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC), and Global Registry of Acute Coronary Events scores (GRACE) models. RESULTS: Ten predictors were identified: left ventricular dysfunction (hazard ratio [HR], 2.3), bare-metal stent (HR, 2.0), Killip class ≥II (HR, 1.9), renal insufficiency (HR, 1.8), previous stroke (HR, 1.6), regional wall-motion- score >20 on echocardiography (HR, 1.5), body mass index ≤24 kg/m2 (HR, 1.4), age ≥70 years (HR, 1.4), prior coronary heart disease (HR, 1.4), and diabetes (HR, 1.4). Compared with the previous models, the KorMI system had good discrimination (time-dependent C statistic, 0.759) and showed reasonable goodness-of-fit by Hosmer-Lemeshow test (p=0.84). Moreover, the continuous-net reclassification improvement varied from −27.3% to −19.1%, the integrated discrimination index varied from −2.1% to −0.9%, and the median improvement in risk score was from −1.0% to −0.4%. CONCLUSIONS: The KorMI system would be a useful tool for predicting outcomes in survivors treated with guideline-adherent optimal therapies after AMI.

Risk Scoring System to Assess Outcomes in Patients Treated with Contemporary Guideline-Adherent Optimal Therapies after Acute Myocardial Infarction

BACKGROUND AND OBJECTIVES@#A risk prediction is needed even in the contemporary era of acute myocardial infarction (AMI). We sought to develop a risk scoring specific for patients with AMI being treated with guideline-adherent optimal therapies, including percutaneous coronary intervention and all 5 medications (aspirin, thienopyridine, β-blocker, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, and statin).@*METHODS@#From registries, 12,174 AMI patients were evaluated. The primary outcome was 1-year all-cause death or AMI. The Korea Working Group in Myocardial Infarction (KorMI) system was compared with the Assessment of Pexelizumab in Acute Myocardial Infarction (APEX AMI), Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC), and Global Registry of Acute Coronary Events scores (GRACE) models.@*RESULTS@#Ten predictors were identified: left ventricular dysfunction (hazard ratio [HR], 2.3), bare-metal stent (HR, 2.0), Killip class ≥II (HR, 1.9), renal insufficiency (HR, 1.8), previous stroke (HR, 1.6), regional wall-motion- score >20 on echocardiography (HR, 1.5), body mass index ≤24 kg/m2 (HR, 1.4), age ≥70 years (HR, 1.4), prior coronary heart disease (HR, 1.4), and diabetes (HR, 1.4). Compared with the previous models, the KorMI system had good discrimination (time-dependent C statistic, 0.759) and showed reasonable goodness-of-fit by Hosmer-Lemeshow test (p=0.84). Moreover, the continuous-net reclassification improvement varied from −27.3% to −19.1%, the integrated discrimination index varied from −2.1% to −0.9%, and the median improvement in risk score was from −1.0% to −0.4%.@*CONCLUSIONS@#The KorMI system would be a useful tool for predicting outcomes in survivors treated with guideline-adherent optimal therapies after AMI.

Characterization of Specific IgA Response to Antigenic Determinants of Helicobacter pylori Urease Encoded by ureA and ureB in Children

Helicobacter pylori (H. pylori), a causative agent of chronic gastritis and gastric cancer, has several virulent factors for own survival and progression toward gastric diseases in human stomach. Of those, H. pylori produces mainly urease (10~15% total protein weight) that neutralize the gastric acid for survival. Here, we identified the antigenic epitope of urease and then developed an ELISA using the antigen including the epitope of urease. We identified the antigenic epitope of urease that induces IgA antibodies in human using truncated mutants. Eight kinds of serially-truncated mutant of UreA and UreB were prepared and subjected to immunoblot using pooled sera of patients with gastric disorders. UreBEnd protein containing UreB epitope was produced and investigated its diagnostic value via ELISA in children. As a result, mutants having last 24 amino acid residues of UreB carboxyl terminus deleted did not show IgA-reactive band. The clones that contained the downstream of 448(th) amino acid in UreB showed IgA-reactive band. The serodiagnostic value of the UreBEnd recombinant protein including identified epitope was confirmed via IgA ELISA and shown to have 97% sensitivity and 100% specificity. These results demonstrated that carboxyl terminal region of UreB carries an antigenic epitope for IgA response in human. It may be useful for detecting H. pylori infection with improved test accuracy and minimum use of endoscopy.

Helicobacter pylori Antigens Inducing Early Immune Response in Infants

To identify the Helicobacter pylori antigens operating during early infection in sera from infected infants using proteomics and immunoblot analysis. Two-dimensional (2D) large and small gel electrophoresis was performed using H. pylori strain 51. We performed 2D immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) antibody immunoblotting using small gels on sera collected at the Gyeongsang National University Hospital from 4–11-month-old infants confirmed with H. pylori infection by pre-embedding immunoelectron microscopy. Immunoblot spots appearing to represent early infection markers in infant sera were compared to those of the large 2D gel for H. pylori strain 51. Corresponding spots were analyzed by matrix-assisted laser desorption/ionization time of flight-mass spectrometry (MALDI-TOF-MS). The peptide fingerprints obtained were searched in the National Center for Biotechnology Information (NCBI) database. Eight infant patients were confirmed with H. pylori infection based on urease tests, histopathologic examinations, and pre-embedding immunoelectron microscopy. One infant showed a 2D IgM immunoblot pattern that seemed to represent early infection. Immunoblot spots were compared with those from whole-cell extracts of H. pylori strain 51 and 18 spots were excised, digested in gel, and analyzed by MALDI-TOF-MS. Of the 10 peptide fingerprints obtained, the H. pylori proteins flagellin A (FlaA), urease β subunit (UreB), pyruvate ferredoxin oxidoreductase (POR), and translation elongation factor Ts (EF-Ts) were identified and appeared to be active during the early infection periods. These results might aid identification of serological markers for the serodiagnosis of early H. pylori infection in infants.

Role of Quantitative Wall Motion Analysis in Patients with Acute Chest Pain at Emergency Department

BACKGROUND: Evaluation of acute chest pain in emergency department (ED), using limited resource and time, is still very difficult despite recent development of many diagnostic tools. In this study, we tried to determine the applicability of new semi-automated cardiac function analysis tool, velocity vector imaging (VVI), in the evaluation of the patients with acute chest pain in ED. METHODS: We prospectively enrolled 48 patients, who visited ED with acute chest pain, and store images to analyze VVI from July 2005 to July 2007. RESULTS: In 677 of 768 segments (88%), the analysis by VVI was feasible among 48 patients. Peak systolic radial velocity (V(peak)) and strain significantly decreased according to visual regional wall motion abnormality (V(peak), 3.50 ± 1.34 cm/s for normal vs. 3.46 ± 1.52 cm/s for hypokinesia, 2.51 ± 1.26 for akinesia, p < 0.01; peak systolic radial strain -31.74 ± 9.15% fornormal, -24.33 ± 6.28% for hypokinesia, -20.30 ± 7.78% for akinesia, p < 0.01). However, the velocity vectors at the time of mitral valve opening (MVO) were directed outward in the visually normal myocardium, inward velocity vectors were revealed in the visually akinetic area (V(MVO), -0.85 ± 1.65 cm/s for normal vs. 0.10 ± 1.46 cm/s for akinesia, p < 0.001). At coronary angiography, V(MVO) clearly increased in the ischemic area (V(MVO), -0.88+1.56 cm/s for normal vs. 0.70 + 2.04 cm/s for ischemic area, p < 0.01). CONCLUSION: Regional wall motion assessment using VVI showed could be used to detect significant ischemia in the patient with acute chest pain at ED.

Isolation and Genetic Characterization of Orientia tsutsugamushi from Scrub Typhus Patients in Gyeongsangnam-do, Korea

Orientia tsutsugamushi (O. tsutsugamushi), which is endemic to an Asia-Pacific region, has increased its incidence and caused annually around 10 thousand patients infected with scrub typhus in Korea in the past several years. In the present study, we isolated 44 O. tsutsugamushi from the patients with febrile illness accompanied with or without an eschar in Gyeongsangnam-do, Korea. These isolates were characterized by genetic analysis of the major outer membrane protein, the 56-kDa type-specific antigen (tsa56), which is unique to O. tsutsugamushi. Two types of sequences of tsa56, designated by JJ1 and JJ2, were determined from 37 and 7 isolates of the 44 isolates, respectively. JJ1 and JJ2 showed 74.7~90.8% identity in nucleotide sequence and 66.1~90.5% identity in amino acid sequence with 33 reference strains except for Boryong and Kuroki. JJ1 and JJ2 had 100 and 99.9% nucleotide identity to Boryong strain, and 99.9 and 99.8% to Kuroki, which has been known to be similar to Boryong, respectively. In addition, they showed 77.9~ 81.4% nucleotide identity with the cluster of Gilliam-related genotypes, whereas they showed higher nucleotide identity (89.6~90.8%) with the cluster of Karp-related genotypes. To our knowledge, this is the first report to isolate O. tsutsugamushi and characterize their genotype as the Boryong in Jinju and West Gyeongsangnam-do, Korea, even though it has been reported that the Boryong was the predominant genotype in isolates from chiggers, domestic rodents, and patients in the southern part of Korea. Furthermore, our isolates could be useful source to study on the pathophysiology and epidemiology of scrub typhus in Korea.

Numbness after Transradial Cardiac Catheterization: the Results from a Nerve Conduction Study of the Superficial Radial Nerve

BACKGROUND AND OBJECTIVES: Numbness on the hand occurs infrequently after a transradial cardiac catheterization (TRC). The symptom resembles that of neuropathy. We, therefore, investigated the prevalence, the predicting factors and the presence of neurological abnormalities of numbness, using a nerve conduction study (NCS). SUBJECTS AND METHODS: From April to December 2013, all patients who underwent a TRC were prospectively enrolled. From among these, the patients who experienced numbness on the ipsilateral hand were instructed to describe their symptoms using a visual analogue scale; subsequently, NCSs were performed on these patients. RESULTS: Of the total 479 patients in the study sample, numbness occurred in nine (1.8%) following the procedure. The NCS was performed for eight out of the nine patients, four (50%) of which had an abnormal NCS result at the superficial radial nerve. A larger sheath and history of myocardial infarction (p=0.14 and 0.08 respectively) tended towards the occurrence of numbness; however, only the use of size 7 French sheaths was an independent predictor for the occurrence of numbness (odds ratio: 5.50, 95% confidence interval: 1.06-28.58, p=0.042). The symptoms disappeared for all patients but one, within four months. CONCLUSION: A transient injury of the superficial radial nerve could be one reason for numbness after a TRC. A large sheath size was an independent predictor of numbness; therefore, large sized sheaths should be used with caution when performing a TRC.

Proteome Analysis of a Catalase-deficient Isogenic Mutant of Helicobacter pylori 26695

Helicobacter pylori, a gram-negative bacterium, is a causative agent of gastroduodenal diseases of human. Human immune system produces harmful reactive oxygen species to kill this bacterium that locates the microaerophilic mucous layer. H. pylori harbors various antioxidant enzymes including SodB, KatA and AhpC to protect the oxygen toxicity. We removed the catalase gene (katA) from H. pylori 26695 genome, and the change of profile of the gene expression of the mutant was analyzed by high resolution 2-DE followed by matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), tandem MS and microarray analysis. Eleven and 37 genes were upregulated and downregulated in the mutant respectively, either transcriptionally or translationally. Expression level of pfr and hp1588 that were decreased on protein level in the mutant was confirmed by RT-PCR analysis.

Helicobacter pylori: Bacterial Strategy for Incipient Stage and Persistent Colonization in Human Gastric Niches

Helicobacter pylori (H. pylori) undergoes decades long colonization of the gastric mucosa of half the population in the world to produce acute and chronic gastritis at the beginning of infection, progressing to more severe disorders, including peptic ulcer disease and gastric cancer. Prolonged carriage of H. pylori is the most crucial factor for the pathogenesis of gastric maladies. Bacterial persistence in the gastric mucosa depends on bacterial factors as well as host factors. Herein, the host and bacterial components responsible for the incipient stages of H. pylori infection are reviewed and discussed. Bacterial adhesion and adaptation is presented to explain the persistence of H. pylori colonization in the gastric mucosa, in which bacterial evasion of host defense systems and genomic diversity are included.

Purification and Characterization of Helicobacter pylori gamma-Glutamyltranspeptidase

Gamma-glutamyltranspeptidase (GGT) was purified to electrophoretic homogeneity from the cell extract of H. pylori. The purified enzyme consisted of heavy and light subunits with molecular weights of 38 kDa and 21 kDa, respectively. N-terminal amino acid sequence of heavy and light subunits revealed that H. pylori GGT was processed into 3 parts for a signal peptide of 27 amino acid residues, a heavy subunit of 352 residues, and a light subunit of 188 residues during translation. The reaction rate for hydrolysis of gamma-GpNA was 84.4 micromol/min per milligram of protein, and that for the gamma-glutamyl transfer from gamma-GpNA to gly-gly was 23.8 micromol/min per milligram of protein. The apparent Km values of H. pylori GGT for gamma-glutamyl compounds were on the order of 10-3 to 10-4 M and those for acceptor peptides and amino acids were on the order of 10-1 to 10-2 M. The GGT protein kept approximately 80% of the initial enzymatic activity on incubation at 60degrees C for 15 min. The optimum temperature and pH for reactions of both hydrolysis and transpeptidation were 40degrees C and 9.0, respectively. The transpeptidation and hydrolysis reactions catalyzed by H. pylori GGT were strongly inhibited by L-Gln and moderately inhibited by L-Ala, L-Ser, beta-chloro-L-Ala, and L-Glu. These results demonstrated that the biochemical properties of H. pylori GGT are different from those of other bacterial GGTs. Further, H. pylori GGT might degrade glutathione in the gastric mucous layer of humans if the enzyme could be secreted in the bacterial niches.

Usefulness of Quantitative Analysis of Computed Tomography Pulmonary Angiography as a Predictor of Prognosis of Acute Pulmonary Embolism

PURPOSE: We evaluated the usefulness of quantitative analysis of computed tomography (CT) pulmonary angiography as a predictor of the prognosis of acute pulmonary embolism (PTE). METHODS: We performed a retrospective analysis of 55 patients who visited our emergency department from January 2000 to November 2007 who were confirmed with PTE by CT pulmonary angiography. Two radiologists blinded to patient outcome measured CT parameters including the diameter of vessels and chambers, and the quantified pulmonary artery (PA) clot load score on the basis of embolus size and location. CT parameters and other clinical predictors were analyzed to determine their ability to predict major adverse event (MAE). RESULTS: Of the 55 patients, 16 (29.1%) had a MAE PTE related shock, intubation, death, thrombolysis, right ventricular (RV) dysfunction within 30 days). Geneva score (odds ratio 2.5, 95% CI 1.18-5.29, p=0.02) and PA clot load score (odds ratio 1.64, 95% CI 1.18-2.27, p<0.01) were strong independent predictors of MAE. The cut-off value of Geneva and PA clot load scores were 4.5 and 19.0, respectively, and the area under the ROC curve were 0.697 (0.546~0.848) and 0.908 (0.828-0.988), respectively. CONCLUSION: Geneva and PA clot load score are significant predictors of PTE related shock, intubation, death, thrombolysis, and RV dysfunction within 30 days. CT pulmonary angiography is a useful predictor for the prognosis of PTE as well as a useful diagnostic tool.

The Relationship of P2Y1 ADP Receptor Polymorphisms and Ischemic Vascular Disease

BACKGROUND: The platelet ADP receptor P2Y1 plays a key role in platelet aggregation. METHODS: We tested eight sites of P2Y1 and studied the possible link between the presence of P2Y1 polymorphisms and the risk of is chemic vascular disease in a case-control study. The polymorphisms A1622G, C647G and C2259G were selected according to linkage disequilibrium. We evaluated 275 patients with is chemic cerebrovascular disease and 275 control subjects. We also evaluated 171 patients with acute myocardial infarction (AMI), 166 patients with unstable angina (UA), 173 patients with stable angina (SA) and 188 control subjects. RESULTS: For the cerebrovascular disease patients, A1622G AA, AG [odds ratio (OR), 1.170; 95% confidence interval (CI), 0.784 to 1.748] and GG (OR, 1.031; 95% CI, 0.554 to 1.918) did not show any difference between the case and control subjects. C647G CC, CG (OR, 0.995; 95% CI, 0.639 to 1.550) and GG (OR, 1.012; 95% CI, 0.450 to 2.277) did not show any difference between the case and control subjects. C2259G CC, CG (OR, 0.619; 95% CI, 0.354 to 1.082) and GG did not show any difference between the case and control subjects. For coronary artery disease patients, C2259G GG, CG (for AMI patients OR, 0.880, 95% CI, 0.384 to 2.016; for UA patients, OR, 0.885, 95% CI, 0.410 to 1.911; for SA patients, OR, 1.156, 95% CI, 0.534 to 2.501) and CC did not show any difference between AMI, UA and SA patients and each control subject. C647G GG, CG (for AMI patients OR, 1.351, 95% CI, 0.731 to 2.497; for UA patients OR, 1.292, 95% CI, 0.723 to 2.309; for SA patients OR, 0.977, 95% CI, 0.530 to 1.803) and CC (for AMI patients OR, 0.355, 95% CI, 0.093 to 1.358; for UA patients OR, 0.645, 95% CI, 0.205 to 2.028; for SA patients OR, 0.385, 95% CI, 0.113 to 1.311) did not show any difference between AMI, UA and SA patients and each control subject. A1622G AA, AG (for AMI patients OR, 1.416, 95% CI, 0.786 to 2.549; for UA patients OR, 1.079, 95% CI, 0.611 to 1.904; for SA patients OR, 0.958, 95% CI, 0.529 to 1.732) and GG (for AMI patients OR, 0.525, 95% CI, 0.195 to 1.411; for UA patients OR, 0.568, 95% CI, 0.231 to 1.401; for SA patients OR, 0.441, 95% CI, 0.169 to 1.154) did not show any difference between AMI, UA and, SA patients and the control subjects. CONCLUSION: The distribution of P2Y1 polymorphisms did not show any association with ischemic vascular disease.

Therapeutic Angiogenesis by Intramyocardial Injection of pCK-VEGF165 in Pigs / 대한흉부외과학회지

BACKGROUND: Gene therapy is a new and promising option for the treatment of severe myocardial ischemia by therapeutic angiogenesis. The goal of this study was to elucidate the efficacy of therapeutic angiogenesis by using VEGF165 in large animals. MATERIALS AND METHOD: Twenty-one pigs that underwent ligation of the distal left anterior descending coronary artery were randomly allocated to one of two treatments: intramyocardial injection of pCK-VEGF (VEGF) or intramyocardial injection of pCK-Null (Control). Injections were administered 30 days after ligation. Seven pigs died during the trial, but eight pigs from VEGF and six from Control survived. Echocardiography was performed on day 0 (preoperative) and on days 30 and 60 following coronary ligation. Gated myocardial single photon emission computed tomography imaging (SPECT) with 99mTc-labeled sestamibi was performed on days 30 and 60. Myocardial perfusion was assessed from the uptake of 99mTc-labeled sestamibi at rest. Global and regional myocardial function as well as post-infarction left ventricular remodeling were assessed from segmental wall thickening; left ventricular ejection fraction (EF); end systolic volume (ESV); and end diastolic volume (EDV) using gated SPECT and echocardiography. Myocardium of the ischemic border zone into which pCK plasmid vector had been injected was also sampled to assess micro-capillary density. RESULT: Micro-capillary density was significantly higher in the VEGF than in Control (386+/-110/mm2 vs. 291+/-127/mm2; p <0.001). Segmental perfusion increased significantly from day 30 to day 60 after intramyocardial injection of plasmid vector in VEGF (48.4+/-15.2% vs. 53.8+/-19.6%; p <0.001), while no significant change was observed in the Control (45.1+/-17.0% vs. 43.4+/-17.7%; p=0.186). This resulted in a significant difference in the percentage changes between the two groups (11.4+/-27.0% increase vs. 2.7+/-19.0% decrease; p=0.003). Segmental wall thickening increased significantly from day 30 to day 60 in both groups; the increments did not differ between groups. ESV measured using echocardiography increased significantly from day 0 to day 30 in VEGF (22.9+/-9.9 mL vs. 32.3+/-9.1 mL; p=0.006) and in Control (26.3+/-12.0 mL vs. 36.8+/-9.7 mL; p=0.046). EF decreased significantly in VEGF (52.0+/-7.7% vs. 46.5+/-7.4%; p=0.004) and in Control (48.2+/-9.2% vs. 41.6+/-10.0%; p=0.028). There was no significant change in EDV. The interval changes (days 30~60) of EF, ESV, and EDV did not differ significantly between groups both by gated SPECT and by echocardiography. CONCLUSION: Intramyocardial injection of pCK-VEGF165 induced therapeutic angiogenesis and improved myocardial perfusion. However, post-infarction remodeling and global myocardial function were not improved.

Effect of angiotensin converting enzyme and nitric oxide synthase polymorphisms and the effect of interaction between the polymorphisms on the restensois after coronary angioplasty in Korea / 대한내과학회지

BACKGROUND: Intimal hyperplasia and vascular remodeling are major mechanisms of restenosis after coronary artery angioplasty. Angiotensin II causes restenosis by stimulating cell proliferation and vascular constriction and nitric oxide prevents restenosis by inhibiting cell proliferation and stimulating vascular dilatation. Angiotensin converting enzyme (ACE) and nitric oxide synthase (NOS) are the main determinants of the activity of the angiotensin II and the nitric oxide. In this study, we tested whether the genetic polymorphisms of the ACE and the NOS gene are the risk factors of restenosis and whether the effect of the genetic polymorphisms in stent group is different from that in balloon angioplasty group. We also tested whether there are interactions among the polymorphisms. METHODS: We determined ACE I/D polymorphism and NOS A/B and G/T polymorphism in 219patients (77 patients (81 lesions) in stent group and 142 patients (181 lesions) in balloon angioplasty group) who underwent PTCA and follow up coronary angiography in Seoul national university hospital from January 1996 to May 1999. RESULTS: Restenosis (50% of reference diameter) was observed in 78/262(30%) lesions (18/81(22%) lesions in stent group, 60/181(33%) lesions in balloon angioplasty group). ACE DD genotype is the significant risk factor for increment of late luminal loss and loss index in stent group. In stent group, means of the late luminal loss and loss index of the lesions of the DD genotype are 1.12+/-0.61mm and 74.7+/-38.3% and those of the non-DD genotype are 0.72+/-0.77mm and 44.9+/-67.5% but DD genotype is not the risk factor for restenosis after balloon angioplasty. The restenosis rate, late luminal loss and loss index are not significantly different according to NOS polymorphisms. No significant interaction among the polymorphisms is observed. CONCLUSION: ACE DD genotype is a significant risk factor for restenosis after stent insertion but is not a risk factor for restenosis after balloon angioplasty in Korean. This result reflects the different mechanism of restenosis after stent insertion and balloon angioplasty. NOS polymorphisms are not associated with restenosis and no interaction between the polymorphisms is observed.

eNOS gene polymorphism in patients with acute coronary syndrome or variant angina in Korean / 대한내과학회지

BACKGROUND: Nitric oxide, also known as endothelial derived relaxing factor(EDRF), regulates the vascular tone and inhibits the proliferation of vascular smooth muscle cells and platelet adhesions and endothelium-leukocyte interactions. Thus, nitric oxide may be involved in the pathogenesis of atherosclerosis and vasospasm. We analyzed the genotype distributions of two eNOS gene polymorphisms in normal healthy Koreans and compared it with those in the patients with acute coronary syndrome and variant angina. METHODS: We analyzed the two eNOS polymorphisms (eNOS A/B polymorphism is the variable numbers of tandem repeat in intron 4 and eNOS T/G polymorphism is a mis-sense mutation in exon 7) using PCR and clinical characteristics of the risk factors for coronary artery disease in 142 normal healthy Koreans and 164 patients with acute coronary syndrome and 104 patients with variant angina. RESULTS: The genotype distribution of A/B polymorphism of eNOS gene, A/A, A/B, B/B was 4.9%, 21.1%, 74% in control group and 2.4%, 12.8%, 84.8% in the patients with acute coronary syndrome(p=0.02) and 2.9%, 16.3%, 80.8% in the patients with variant angina(p=NS), respectively. The genotype distribution of T/G polymorphism of eNOS gene, T/T, T/G, G/G was 1.4%, 15.5%, 83.1% in control group and 0.6%, 21.3%, 78.1% in the patients with acute coronary syndrome(p=NS) and 0%, 18.3%,81.7% in the patients with variant angina(p=NS), respectively. The odds ratio for acute coronary syndrome of non B/B(A/A & A/B) to B/B was 0.489 (95% CI : 0.257-0.928). We found that age, sex (male), diabetes mellitus, hyperlipidemia, smoking, B/B genotype were independent risk factors for acute coronary syndrome. But, in variant angina, smoking was the only significant independent risk factor(odds ratio=5.934, 95% CI 2.843-12.388, p< 0.05). CONCLUSION: The B/B genotype frequency of eNOS gene was significantly higher in patients with acute coronary syndrome than in normal controls. But neither A/B nor T/G polymorphism of eNOS gene was associated with variant angina. These results suggest that eNOS gene may play some roles in the pathogenesis of ACS rather than vasospasm.

Effect of lipoprotein lipase gene polymorphism on lipid profile and body mass index in healthy Korean adult / 대한내과학회지

BACKGROUND: Lipoprotein lipase(LPL) plays a pivotal role in triglyceride-rich lipoprotein metabolism. It removes TG-rich lipoprotein from circulation by hydrolysing TG and produces active form of HDL. It also affects the development and maintenance of obesity by regulating the fatty acid metabolism of the adipose tissue. Many studies about the association of the genetic variation of LPL and dyslipidemia have been performed, but the results were not consistent. We tried to characterize the phenotypes of the LPL genetic variation in Korean. METHODS: Healthy Korean adults (n=110) were genotyped for Hind III/Pvu II RFLP and Ser447Ter mutation of the LPL gene by PCR-digestion method. We investigated the association of the genetic variations with the lipids, the lipoprotein concentrations and the body mass index(BMI). RESULTS: The allele frequencies of Hind III RFLP, Pvu II RFLP and Ser447Ter mutation were H1:H2=33%:67%, P1:P2=40%:60% and Ser447: Ter447=90%:10%. Ser447Ter mutation carriers had higher HDL cholesterol level than non-carriers (59+/-10mg/dl versus 53+/-11mg/dl, p=0.049) and the Pvu II RFLP is associated with increased body mass index. (P1P1:P1P2:P2P2 = 22.1+/-2.0 kg/m2: 23.5+/-2.7 kg/m2: 24.5+/-2.6 kg/m2, p=0.003) CONCLUSION: The genetic variations of the LPL gene in healthy Korean adult resulted in increased HDL cholesterol and increased BMI. These results were different from previous studies. This difference may reflect the racial difference from the diet and the linkage disequilibrium