Trends in the incidence of hospitalized acute myocardial infarction and stroke in Korea, 2006-2010.

This study attempted to calculate and investigate the incidence of hospitalized acute myocardial infarction (AMI) and stroke in Korea. Using the National Health Insurance claim data, we investigated patients whose main diagnostic codes included AMI or stroke during 2006 to 2010. As a result, we found out that the number of AMI hospitalized patients had decreased since 2006 and amounted to 15,893 in 2010; and that the number of those with stroke had decreased since 2006 and amounted to 73,501 in 2010. The age-standardized incidence rate of hospitalized AMI, after adjustment for readmission, was 41.6 cases per 100,000-population in 2006, and had decreased to 29.4 cases in 2010 (for trend P < 0.001). In the case of stroke was estimated at 172.8 cases per 100,000-population in 2006, and had decreased to 135.1 cases in 2010 (for trend P < 0.001). In conclusion, the age-standardized incidence rates of both hospitalized AMI and stroke in Korea had decreased continuously during 2006 to 2010. We consider this decreasing trend due to the active use of pharmaceuticals, early vascular intervention, and the national cardio-cerebrovascular disease care project as the primary and secondary prevention efforts.

Influenza-related mortality among adults aged 25-54 years with AIDS in South Africa and the United States of America.

BACKGROUND: Data are limited on human immunodeficiency virus (HIV)-associated influenza burden in sub-Saharan Africa and the impact of highly active antiretroviral therapy (HAART). We compared influenza-related mortality in adults with AIDS in South Africa and the United States in the pre-HAART era and evaluated mortality trends after HAART introduction in the United States. METHODS: Monthly all-cause and pneumonia and influenza (P&I) mortality rates were compiled for adults with AIDS aged 25-54 years in South Africa (1998-2005) and the United States (pre-HAART era, 1987-1994; HAART era, 1997-2005). We estimated influenza-related deaths as excess mortality above a model baseline during influenza epidemic periods. Influenza-related mortality rates in adults with AIDS were compared with rates for age peers in the general population and adults ≥65 years old. RESULTS: In the United States before HAART, influenza-related mortality rates in adults with AIDS were 150 (95% confidence interval [CI], 49-460) and 208 (95% CI, 74-583) times greater than in the general population for all-cause and P&I deaths, respectively, and 2.5 (95% CI, 0.9-7.2) and 4.1 (95% CI, 1.4-13) times higher than in elderly adults. After HAART introduction , influenza-related mortality in adults with AIDS dropped 3-6-fold but remained elevated compared with the general population (all-cause relative risk [RR], 44 [95% CI, 16-121]); P&I RR, 73 [95% CI, 47-113]). Influenza-related mortality in South African adults with AIDS in recent years was similar to that in the United States in the pre-HAART era. CONCLUSIONS: Adults with AIDS experience substantially elevated influenza-associated mortality, which declines with widespread HAART introduction but does not disappear. These data support increased access to HAART and influenza vaccination for HIV-infected adults.

The 8-hydroxydeoxyguanosine concentrations according to hormone therapy and S326C polymorphism of OGG1 gene in postmenopausal women.

BACKGROUND: The 8-hydroxydeoxyguanosine (8-OHdG) is widely used for determination of DNA damage since it is excised from oxidative damaged DNA with endonuclease repair enzymes coded by 8-oxoguanine DNA N-glycosylase gene (OGG1). The present study aimed at investigating whether hormone therapy (HT) may influence on the blood/urinary 8-OHdG levels and whether the level of 8-OHdG is different according to OGG1 S326C polymorphism in postmenopausal women receiving HT. METHODS: In 102 postmenopausal women receiving HT, the 8-OHdG levels were measured in the blood and urine using high performance liquid chromatography (HPLC) before HT and 3 months after HT. The genotyping of the S326C polymorphism of the OGG1 was performed by polymerase chain reaction (PCR) and restriction enzyme fragment length polymorphism (RFLP) analysis. RESULTS: After HT, mean blood 8-OHdG level significantly decreased compared to those before HT (P=0.003), while urinary 8-OHdG level did not show any difference according to HT. Pre-HT level of 8-OHdG was not different according to OGG1 genotypes and similar finding was demonstrated in post-HT 8-OHdG concentration. CONCLUSIONS: These findings imply that hormone therapy can reduce blood 8-OHdG concentration, one of the markers of oxidative damage. Further study is needed to confirm this association in larger population.

Melatonin promotes osteoblastic differentiation through the BMP/ERK/Wnt signaling pathways.

Although melatonin has a variety of biological actions such as antitumor, antiangiogenic, and antioxidant activities, the osteogenic mechanism of melatonin still remains unclear. Thus, in the present study, the molecular mechanism of melatonin was elucidated in the differentiation of mouse osteoblastic MC3T3-E1 cells. Melatonin enhanced osteoblastic differentiation and mineralization compared to untreated controls in preosteoblastic MC3T3-E1 cells. Also, melatonin increased wound healing and dose-dependently activated osteogenesis markers such as runt-related transcription factor 2 (Runx2), osteocalcin (OCN), bone morphogenic protein (BMP)-2 and -4 in MC3T3-E1 cells. Of note, melatonin activated Wnt 5 α/ß, ß-catenin and the phosphorylation of c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) in a time-dependent manner while it attenuated phosphorylation of glycogen synthase kinase 3 beta (GSK-3ß) in MC3T3-E1 cells. Consistently, confocal microscope observation revealed that BMP inhibitor Noggin blocked melatonin-induced nuclear localization of ß-catenin. Furthermore, Western blotting showed that Noggin reversed activation of ß-catenin and Wnt5 α/ß and suppression of GSK-3ß induced by melatonin in MC3T3-E1 cells, which was similarly induced by ERK inhibitor PD98059. Overall, these findings demonstrate that melatonin promotes osteoblastic differentiation and mineralization in MC3T3-E1 cells via the BMP/ERK/Wnt pathways.

Treatment of 10-mm-Deep or Greater Uncontained Tibial Bone Defects in Primary Total Knee Reconstruction without Metal Augmentation: Autologous Oblique Structural Peg Bone and Cancellous Chip Bone Grafting.

BACKGROUD: In this study, we report satisfactory clinical and radiological outcomes after autologous oblique structural peg bone and cancellous chip bone grafting without metal augmentation, including the use of a metal wedge, block, or additional stem, for patients with ≥ 10-mm-deep uncontained medial proximal tibial bone defects in primary total knee replacement. METHODS: The study group included 40 patients with primary total knee replacement with ≥ 10-mm-deep uncontained tibial bone defects who underwent autologous oblique structural peg bone and cancellous chip bone grafting and were followed-up for at least 1 year. Tibial cutting was performed up to a depth of 10 mm from the articular surface of the lateral tibial condyle, after which the height and area of the remaining bone defect in the medial condyle were measured. The bone defect was treated by making a peg bone and chip bone using excised segments of the tibia and femur. In all cases, the standard tibial stem and full cemented fixation techniques were used without metal augmentation. Preoperative and final follow-up radiologic changes and clinical measures were compared, and prosthesis loosening and bone union were checked radiologically at final follow-up. RESULTS: The mean depth of the bone defects was 10.9 mm, and the mean percentage of the area occupied by bone defects in the axial plane was 18.4%. The mean mechanical femorotibial angle was corrected from 19.5° varus preoperatively to 0.2° varus postoperatively (p < 0.002). There was no prosthesis loosening, and all cases showed bone union at the 1-year postoperative follow-up. CONCLUSIONS: Even in patients with uncontained tibial bone defects ≥ 10-mm deep in primary total knee replacement, if the defect occupies less than 30% of the cut surface, autologous oblique structural peg bone and cancellous chip bone grafting can be used to achieve satisfactory outcomes with a standard tibial stem and no metal augmentation.

Elevated influenza-related excess mortality in South African elderly individuals, 1998-2005.

BACKGROUND: Although essential to guide control measures, published estimates of influenza-related seasonal mortality for low- and middle-income countries are few. We aimed to compare influenza-related mortality among individuals aged ≥65 years in South Africa and the United States. METHODS: We estimated influenza-related excess mortality due to all causes, pneumonia and influenza, and other influenza-associated diagnoses from monthly age-specific mortality data for 1998-2005 using a Serfling regression model. We controlled for between-country differences in population age structure and nondemographic factors (baseline mortality and coding practices) by generating age-standardized estimates and by estimating the percentage excess mortality attributable to influenza. RESULTS: Age-standardized excess mortality rates were higher in South Africa than in the United States: 545 versus 133 deaths per 100,000 population for all causes (P<.001) and 63 vs 21 deaths per 100,000 population for pneumonia and influenza (P=.03). Standardization for nondemographic factors decreased but did not eliminate between-country differences; for example, the mean percentage of winter deaths attributable to influenza was 16% in South Africa and 6% in the United States (P<.001). For all respiratory causes, cerebrovascular disease, and diabetes, age-standardized excess death rates were 4-8-fold greater in South Africa than in the United States, and the percentage increase in winter deaths attributable to influenza was 2-4-fold higher. CONCLUSIONS: These data suggest that the impact of seasonal influenza on mortality among elderly individuals may be substantially higher in an African setting, compared with in the United States, and highlight the potential for influenza vaccination programs to decrease mortality.

Influence of NQO1, ALDH2, and CYP2E1 genetic polymorphisms, smoking, and alcohol drinking on the risk of lung cancer in Koreans.

OBJECTIVES: We investigated the association of genetic polymorphisms of NQO1, ALDH2, CYP2E1, and the combined genotype of these genes on lung cancer risk, and also evaluated the association after stratification by cumulative smoking amounts and alcohol drinking levels. METHODS: The case-control study was performed in 387 lung cancer patients and 387 age- and sex-matched cancer-free controls. Direct interview was conducted and the genotypes of NQO1, ALDH2, and CYP2E1 were investigated using PCR-RFLP or 5'-nuclease activity assay. RESULTS: The proportion of individuals with occupational history of mining was significantly higher in cases than in controls. The risk of lung cancer was significantly lower in light-drinkers (<108 g/week) than non-drinkers. The NQO1 Pro/Ser + Ser/Ser genotype showed an increased risk for lung cancer with a marginal significance (OR = 1.35, 95% CI = 0.99-1.86) compared with NQO1 Pro/Pro genotype. In heavy-smokers, the combination of NQO1 Pro/Ser + Ser/Ser and CYP2E1 c1/c1 genotype was associated with a significantly increased risk for lung cancer (OR = 2.25, 95% CI = 1.14-4.43) compared with those of NQO1 Pro/Pro and CYP2E1 c1/c2 + c2/c2 genotype. We found a significant interaction between alcohol drinking level and the CYP2E1 genotype (P = 0.0227). CONCLUSIONS: Our result suggests that the risk of lung cancer is affected by smoking, alcohol drinking, and the genetic polymorphism of NQO1. In particular, genetic polymorphisms for NQO1, CYP2E1, and ALDH2 synergistically with cumulative smoking amounts and alcohol drinking levels interact in the carcinogenesis of lung cancer in Koreans.

Influence of Atlantoaxial Fusion on Sagittal Alignment of the Occipitocervical and Subaxial spines in Os Odontoideum with Atlantoaxial Instability.

Study Design: Retrospective case analysis. Purpose: We hypothesized that larger the C1-C2 fusion angle, greater the severity of the sagittal malalignment of C0-C1 and C2- C7. Overview of Literature: In our experience, instances of sagittal malalignment occur at C0-C1 and C2-C7 following atlantoaxial fusion in patients with Os odontoideum (OO). Methods: We assessed 21 patients who achieved solid atlantoaxial fusion for reducible atlantoaxial instability secondary to OO. The mean patient age at the time of the operation was 42.8 years, and the mean follow-up duration was 4.9 years. Radiographic parameters were preoperatively measured and at the final follow-up. The patients were divided into two groups (A and B) depending on the C1-C2 fusion angle. In group A (n=11), the C1-C2 fusion angle was ≥22°, whereas in group B, it was <22°. The differences in the radiographic parameters of the two groups were evaluated. Results: At the final follow-up, the C1-C2 angle was increased. However, this increase was not statistically significant (18° vs. 22°, p=0.924). The C0-C1 angle (10° vs. 5°, p<0.05) and C2-C7 angle (22° vs. 13°, p<0.05) significantly decreased. The final C1-C2 angle was negatively correlated with the final C0-C1 and C2-C7 angles. The final C0-C1 angle (4° vs. 6°, p<0.05) and C2-C7 angle (8° vs. 20°, p<0.05) were smaller in group A than in group B. After atlantoaxial fusion, the C0-C1 range of motion (ROM; 17° vs. 9°, p<0.05) and the C2-C7 ROM (39° vs. 31°, p<0.05) were significantly decreased. Conclusions: We found a negative association between the sagittal alignment of C0-C1 and C2-C7 after atlantoaxial fusion and the C1-C2 fusion angle along with decreased ROM. Therefore, overcorrection of C1-C2 kyphosis should be avoided to maintain good physiologic cervical sagittal alignment.

Posterior Sublaminar Wiring and/or Transarticular Screw Fixation for Reducible Atlantoaxial Instability Secondary to Symptomatic Os Odontoideum: A Neglected Technique?

STUDY DESIGN: Retrospective case analysis. PURPOSE: We retrospectively evaluated the clinical and radiological outcomes of posterior sublaminar wiring (PSLW) and/or transarticular screw fixation (TASF) for reducible atlantoaxial instability (AAI) secondary to os odontoideum. OVERVIEW OF LITERATURE: Limited information is available about the surgical outcomes of symptomatic os odontoideum with AAI. METHODS: We examined 23 patients (12 women and 11 men) with os odontoideum and reducible AAI. The average age of the patients at the time of the operation was 44.2 years. The average follow-up duration was 4.5 years. Thirteen patients with anterior AAI underwent PSLW alone, while 10 patients with combined (anterior+posterior) AAI underwent PSLW and TASF. An autogenous iliac bone graft was used for all patients. Nine patients complained of neck or suboccipital pain, and 14 complained of myelopathy. RESULTS: Angulational instability (preoperative 18.7°±8.9° vs. postoperative 2.1°±4.6°, p<0.001), translational instability (16.3±4.9 mm vs. 1.8±2.2 mm, p<0.001), and segmental angle of the C1-C2 joint (23.7°±7.2° vs. 28.4°±3.8°, p<0.05) showed significant improvement postoperatively. Neck Visual Analog Scale score (6.2±2.4 vs. 2.5±1.8, p<0.05) and the modified Japanese Orthopedic Association (9.1±3.1 vs. 13.2±2.6, p<0.05) score also improved, with a recovery rate of 51.8%. Among the three patients who developed nonunion and/or wire breakage, one underwent revision surgery with repeat PSLW and was finally able to achieve fusion. The final fusion rate was 91.3%. CONCLUSIONS: PSLW and/or TASF provided satisfactory clinical and radiological outcomes in reducible AAI secondary to os odontoideum without significant neurological complications. Our results suggest that PSLW and/or TASF can be considered a viable surgical option over segmental fixation in highly selected cases of os odontoideum with reducible AAI.

Aryl hydrocarbon receptor gene polymorphisms affect lung cancer risk.

To evaluate the role of genetic polymorphisms of AhR related to the carcinogen metabolism and cell proliferation, genotypes of three AhR polymorphisms Ex1+185A>G, IVS7+33T>G and Ex10+501G>A were determined in 616 lung cancer cases and 616 lung cancer-free controls. When the effect of each AhR allele on lung cancer risk was evaluated, any AhR genotype did not show the association with lung cancer risk. However, when haplotypes were composed of three AhR SNP sites, non-smokers with GGG haplotype (adjusted OR=1.7, 95% CI, 1.06-2.71) and smokers without GGG haplotype (adjusted OR=2.5, 95% CI, 1.64-3.74) showed significantly increased risk of lung cancer compared to non-smokers without GGG haplotype. Moreover, smokers with GGG haplotype showed the highest risk (adjusted OR=3.2, 95% CI, 2.10-4.74). Particularly, the synergistic effect between AhR haplotype and smoking was more apparent in squamous cell carcinoma (adjusted OR=6.1, 95% CI, 2.53-14.68). This result suggests that haplotypes of AhR gene play an important role in the development of lung cancer and there is a synergistic interaction between AhR gene and smoking for lung cancer risk.

Ethanol-induced oxidative DNA damage and CYP2E1 expression in liver tissue of Aldh2 knockout mice.

Excessive alcohol consumption is associated with increased risks of many diseases including cancer. We evaluated oxidative DNA damage in Aldh2 +/+ and Aldh2 -/- mice after they had been subjected to acute ethanol exposure. Olive tail moment, which was measured using a comet assay, was not increased by ethanol treatment in both Aldh2 +/+ and Aldh2 -/- mice. However, after controlling for the effect of ethanol exposure, the Aldh2 genotype was a significant determinant for Olive tail moments. Although the ethanol treatment significantly increased the hepatic 8-OHdG generation in only Aldh2 +/+ mice, the level of 8-OHdG was the highest in Aldh2 -/- ethanol treated mice. The increase in the level of 8-OHdG was associated with hepatic expression of cytochrome P450 2E1 (CYP2E1). The levels of Olive tail moment and the hepatic 8-OHdG in the Aldh2 -/- control group were significantly higher than those of the Aldh2 +/+ control group. The level of CYP2E1 in liver tissue showed a similar pattern to those of the oxidative DNA damage markers. This study shows that acute ethanol consumption increases oxidative DNA damage and that expression of CYP2E1 protein may play a pivotal role in the induction of oxidative DNA damage. The finding that oxidative DNA damage was more intense in Aldh2 -/- mice than in Aldh2 +/+ mice suggests that ALDH2-deficient individuals may be more susceptible than wild-type ALDH2 individuals to ethanol-mediated liver disease, including cancer.

Psychological Vulnerability of Residents of Communities Affected by the Hebei Spirit Oil Spill.

OBJECTIVE: Psychological health is an important issue after disasters. This study aimed to investigate the prevalence of psychological symptoms among 993 residents of Taean District in South Korea after the Hebei Spirit oil spill and to examine determinants of vulnerability in residents' psychological symptoms. METHODS: Symptoms of post-traumatic stress (PTS), depression, suicidal ideation, and anxiety were assessed by questionnaires, and the responses were analyzed by using the survey analysis considering the sampling frame. RESULTS: Among the study subjects, the symptom prevalences of PTS, depression, suicidal ideation, and anxiety were 19.5%, 22.0%, 2.3%, and 4.2%, respectively, and symptoms were higher in people who were female, were older, were less educated, and had lower family income. People with fishery or related occupations compared to those with unrelated livelihoods and people residing in the vicinity of the oil band in the contaminated coastline showed additively increased symptom risks of PTS. Risk of suicidal ideation was predominantly increased in people with fishery or related occupations compared with those with unrelated livelihoods. CONCLUSIONS: Social supports, including compensation for income loss and community mental health programs, and longer follow-up studies are needed for residents in the communities affected by the Hebei Spirit oil spill.

Kimchi and soybean pastes are risk factors of gastric cancer.

AIM: This case-control study investigated the effects of kimchi, soybean paste, fresh vegetables, nonfermented alliums, nonfermented seafood, nonfermented soybean foods, and the genetic polymorphisms of some metabolic enzymes on the risk of gastric cancer in Koreans. METHODS: We studied 421 gastric cancer patients and 632 age- and sex-matched controls. Subjects completed a structured questionnaire regarding their food intake pattern. Polymorphisms of cytochrome P450 1A1 (CYP1A1), cytochrome P450 2E1 (CYP2E1), glutathione S-transferase mu 1 (GSTM1), glutathione S-transferase theta 1 (GSTT1) and aldehyde dehydrogenase 2 (ALDH2) were investigated. RESULTS: A decreased risk of gastric cancer was noted among people with high consumption of nonfermented alliums and nonfermented seafood. On the other hand, consumption of kimchi, and soybean pastes was associated with increased risk of gastric cancer. Individuals with the CYP1A1 Ile/Val or Val/Val genotype showed a significantly increased risk for gastric cancer. Increased intake of kimchi or soybean pastes was a significant risk factor for the CYP1A1 Ile/Ile, the CYP2E1 c1/c1, the GSTM1 non-null, the GSTT1 non-null, or the ALDH2 *1/*1 genotype. In addition, eating soybean pastes was associated with the increased risk of gastric cancer in individuals with the GSTM1 null type. Nonfermented alliums were significant in individuals with the CYP1A1 Ile/Ile, the CYP2E1 c1/c2 or c2/c2, the GSTT1 null, the GSTT1 non-null, or the ALDH2 *1/*2 or *2/*2 genotype, nonfermented seafood was those with the CYP1A1 Ile/Ile, the CYP2E1 c1/c1, the ALDH2 *1/*1 genotype or any type of GSTM1 or GSTT1. In homogeneity tests, the odds ratios of eating kimchi for gastric cancer according to the GSTM1 or GSTT1 genotype were not homogeneous. CONCLUSION: Kimchi, soybean pastes, and the CYP1A1 Ile/Val or Val/Val are risk factors, and nonfermented seafood and alliums are protective factors against gastric cancer in Koreans. Salt or some chemicals contained in kimchi and soybean pastes, which are increased by fermentation, would play important roles in the carcinogenesis of stomach cancer. Polymorphisms of the CYP1A1, CYP2E1, GSTM1, GSTT1, and ALDH2 genes could modify the effects of some environmental factors on the risk of gastric cancer.

A Prospective Randomized Clinical Trial Comparing Bone Union Rate Following Anterior Cervical Discectomy and Fusion Using a Polyetheretherketone Cage: Hydroxyapatite/B-Tricalcium Phosphate Mixture versus Hydroxyapatite/Demineralized Bone Matrix Mixture.

STUDY DESIGN: Prospective randomized noninferiority trial. PURPOSE: To evaluate whether the union rate of anterior cervical discectomy and fusion (ACDF) using a polyetheretherketone (PEEK) cage filled with a mixture of hydroxyapatite (HA) and demineralized bone matrix (DBM) is inferior to that of a mixture of ß-tricalcium phosphate (ß-TCP) and HA. OVERVIEW OF LITERATURE: There have been no clinical trials investigating the outcomes of a mixture of HA and DBM in a PEEK cage in ACDF. METHODS: Eighty-five eligible patients were randomly assigned to group B (n=43), in which a PEEK cage with a mixture of HA and DBM was used, or group C (n=42), in which a PEEK cage with a mixture of HA and ß-TCP was used. The primary study endpoint was the fusion rate, which was assessed with dynamic radiographs and computed tomography (CT) scans. Secondary endpoints included pain intensity using a visual analogue scale, functional outcome using a neck disability index score, laboratory tests of inflammatory profiles, and the infection rate. RESULTS: Seventy-seven patients (38 in group B and 39 in group C) were included in the final analysis. One year postoperatively, bone fusion was achieved in 87% of group B patients and 87% of group C patients on dynamic radiographs, and 87% of group B patients and 72% of group C patients on CT scans (p=1.00 and 0.16, respectively). There were also no between-groups differences with respect to the secondary endpoints. CONCLUSIONS: A HA/DBM mixture inside a PEEK cage can provide noninferior outcomes compared to a HA/TCP mixture in ACDF.

Regional differences in age at menopause between Korean-Korean and Korean-Chinese.

OBJECTIVE: To evaluate the difference in age at menopause between Korean-Korean (KK) women and Korean-Chinese (KC) women. DESIGN: A total of 1,972 participants were recruited: 961 postmenopausal women living in Korea, and 1,011 second- or third-generation emigrants to China. A structured questionnaire was used that included current age (at interview), age at menopause, weight, height, duration of education, socioeconomic status (SES), smoking, alcohol intake, number of children and abortions, etc. For every independent variable, the effect of regional difference (ie, living in Korea or China) on age at menopause was analyzed. Student's t test and chi2 test were applied as appropriate, and multiple regression analyses were performed for significant variables. RESULTS: Age at menopause was significantly higher in KK than KC (49.3 +/- 3.5 y vs 48.9 +/- 3.1 y, P = 0.011). Body mass index (BMI) and number of abortions were also higher in KK (23.3 +/- 2.7 vs 23.1 +/- 2.6, P = 0.021; 1.3 +/- 1.7 vs 0.2 +/- 0.7, P = 0.0001). Duration of education was significantly longer in KK. Smokers showed a significantly earlier menopause onset. BMI was significantly and positively correlated with age at menopause, whereas current SES was negatively correlated. When regional differences were assessed in each categorized subgroup, age at menopause showed a significant difference, too. After adjusting for age, SES, BMI, smoking, and number of children, onset of menopause was still earlier in KC (P = 0.0001, R = 0.037). CONCLUSION: KK women were found to have a later onset of menopause than KC women, and our results suggest that, apart from the well-known genetic influence, environmental effects play a significant role in determining age at menopause.

Effects of genetic polymorphisms in metabolic enzymes on the relationships between 8-hydroxydeoxyguanosine levels in human leukocytes and urinary 1-hydroxypyrene and 2-naphthol concentrations.

This study was designed to investigate the relationship between environmental exposure to polycyclic aromatic hydrocarbons (PAHs) and oxidative stress, and to evaluate the effects of cigarette smoking and the genetic polymorphisms of CYP1A1, CYP2E1, GSTM1, NAT2 and UGT1A6 on the relationship. The subjects of this study were 105 healthy Korean males without occupational exposure to PAHs. The 8-hydroxydeoxyguanosine (8-OHdG) level in leukocytes, and urinary 1-hydroxypyrene (1-OHP) and 2-naphthol concentrations, were measured by high-performance liquid chromatography. Genetic polymorphisms of CYP1A1, CYP2E1, GSTM1, NAT2 and UGT1A6 were identified by PCR and PCR-RFLP methods. The 8-OHdG level showed a significant correlation with the 1-OHP concentration in all subjects (p<.001) and in smokers (p<.01), and with the 2-naphthol level in non-smokers (p<.01). The 8-OHdG level was significantly higher in smoking rapid acetylators than in smoking slow or intermediate acetylators, and in individuals with the UGT1A6 wild-type than in those with the UGT1A6 mutant genotype. Significant positive correlations between 8-OHdG and 1-OHP concentrations were found in subjects with every genotype of the CYP1A1 and CYP2E1 genes, with the GSTM1 null-type, with the NAT2 genotype of a rapid acetylator, and with the UGT1A6 wild-type, respectively. The urinary 2-naphthol level significantly correlated with the 8-OHdG level only in subjects with the GSTM1 null-type. In conclusion, there is a significant correlation between the 8-OHdG level in leukocytes and the urinary 1-OHP concentration in the population not occupationally exposed to PAHs. This relationship is affected by genetic polymorphisms in PAH metabolic enzymes.

Correlation of urinary 1-hydroxypyrene and 2-naphthol with total suspended particulates in ambient air in municipal middle-school students in Korea.

The authors investigated Korean municipal middle school students to ascertain whether urinary 1-hydroxypyrene (1-OHP) and 2-naphthol-markers for polycyclic aromatic hydrocarbon (PAH) exposure-reflect PAHs in ambient air. The authors used the beta-ray absorption method, which is an index of ambient-air PAH exposure, to collect total suspended particulate (TSP) data. The authors measured urinary 1-OHP and 2-naphthol concentrations in 137 nonsmoking students in 4 municipal middle schools within 1 km of ambient air monitoring stations. The median concentrations of urinary 1-OHP and 2-naphthol in the study were 0.09 nmole/mol creatinine and 2.19 micromol/mol creatinine, respectively, and the geometric means were 0.10 nmole/mol creatinine and 2.47 micromol/mol creatinine, respectively. Urinary 1-OHP concentration did not correlate significantly with any TSP index. There were significant correlations between urinary 2-naphthol level and the daily mean TSP level calculated for 2 days before survey, for 1 day before survey, and for the day of survey. These data suggest that urinary 2-naphthol may be a good marker for inhalation exposure to PAHs in ambient air.

Cancer risk in diagnostic radiation workers in Korea from 1996–2002.

This study was aimed to examine the association between the effective radiation dose of diagnostic radiation workers in Korea and their risk for cancer. A total of 36,394 diagnostic radiation workers (159,189 person-years) were included in this study; the effective dose and cancer incidence were analyzed between the period 1996 and 2002. Median (range) follow-up time was 5.5 (0.04-7) years in males and 3.75 (0.04-7) years in females. Cancer risk related to the average annual effective dose and exposure to more than 5 mSv of annual radiation dose were calculated by the Cox proportional hazard model adjusted for occupation and age at the last follow-up. The standardized incidence ratio of cancer in radiation workers showed strong healthy worker effects in both male and female workers. The relative risk of all cancers from exposure of the average annual effective dose in the highest quartile (upper 75% or more of radiation dose) was 2.14 in male workers (95% CI: 1.48-3.10, p-trend: <0.0001) and 4.43 in female workers (95% CI: 2.17-9.04, p-trend: <0.0001), compared to those in the lower three quartiles of radiation exposure dose (less than upper 75% of radiation dose). Cancer risks of the brain (HR: 17.38, 95% CI: 1.05-287.8, p-trend: 0.04) and thyroid (HR: 3.88, 95% CI: 1.09-13.75, p-trend: 0.01) in female workers were significantly higher in the highest quartile group of radiation exposure compared to those in the lower three quartiles, and the risk of colon and rectum cancers in male workers showed a significantly increasing trend according to the increase of the average annual radiation dose (HR: 2.37, 95% CI: 0.99-5.67, p-trend: 0.02). The relative risk of leukemia in male workers and that of brain cancer in female workers were significantly higher in the group of people who had been exposed to more than 5 mSv/year than those exposed to less than 5 mSv/year (HR: 11.75, 95% CI: 1.08-128.20; HR: 63.11, 95% CI: 3.70-1,075.00, respectively). Although the present study involved a relatively young population and a short follow-up time, statistically significant increased risks of some cancers in radiation workers were found, which warrants a longer follow-up study and more intensive protective measures in this population.

Polycyclic aromatic hydrocarbon-induced oxidative stress, antioxidant capacity, and the risk of lung cancer: a pilot nested case-control study.

AIM: We conducted a pilot nested case-control study to prospectively evaluate the effects of polycyclic aromatic hydrocarbons (PAH) exposure, antioxidant capacity, and oxidative stress on lung carcinogenesis. MATERIALS AND METHODS: Thirty-five patients with lung cancer and 140 age- and sex-matched controls were selected from a sub-cohort of the Korean Multi-center Cancer Cohort. PAH metabolites (1-hydroxypyrene and 2-naphthol), oxidative stress markers, and total antioxidant capacity (TAC) were assessed using urine samples collected at baseline. RESULTS: The levels of urinary PAH metabolites and oxidative stress were not different between cases and controls. Urinary 1-hydroxypyrene and 2-naphthol levels were significantly associated with urinary oxidative stress markers only in lung cancer cases. Individuals with low urinary TAC and high urinary oxidative stress levels had significantly higher risk of lung cancer compared to those with high urinary TAC and low urinary oxidative stress levels. CONCLUSION: Oxidative stress induced by PAH exposure and TAC may be important determinants for the susceptibility to lung cancer.

Utility of fractional exhaled nitric oxide (F(E)NO) measurements in diagnosing asthma.

BACKGROUND: To facilitate the use of fractional exhaled nitric oxide (F(E)NO) as a clinical test, F(E)NO measurements need more clarification. AIM: We sought to evaluate the yield of F(E)NO measurement for the diagnosis of asthma and identify the determinants of F(E)NO in children. METHODS: Two hundred forty five consecutive steroid-naïve patients aged 8-16 years with symptoms suggestive of asthma were included. Children were evaluated using F(E)NO measurements, questionnaires, skin prick tests, spirometries, and methacholine challenge tests. RESULTS: Asthma was diagnosed in 167 children. The sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) of F(E)NO measurements for the diagnosis of asthma at the best cutoff value of 22 ppb were 56.9%, 87.2%, 90.5%, and 48.6%, respectively. At a cutoff value of 42 ppb, specificity and PPV were all 100% but at the cost of very low sensitivity (23.4%) and NPV (37.9%). Both atopy and asthma were identified as independent risk factors associated with high F(E)NO. The association of asthma with high F(E)NO was found only in atopic children because F(E)NO was low in non-atopic children regardless of asthma status. Although highest F(E)NO was observed in atopic asthmatic patients, 28% of these patients had F(E)NO values lower than 22 ppb. CONCLUSION: Atopic asthmatic patients with low F(E)NO values and non-atopic asthmatic patients were responsible for false-negative cases that might contribute to low sensitivity of F(E)NO measurements in diagnosing asthma. High specificity of F(E)NO measurements may help identify patients with atopic asthma among subjects with respiratory symptoms.