Genome-wide association studies for educational attainment have been limited to Europeans, but genetic factors might be largely related to cultural environments and thus dependent on populations. We aimed to identify genetic associations with educational attainment in Koreans. We analyzed genome-wide associations with the schooling years of 8770 individuals who participated in the Korea Association Resource cohort employing a mixed model. The analysis revealed two nucleotide variants (rs6467024 and rs16951883) using a genome-wide significance threshold (P < 5 × 10–8), and six variants (rs9844107, rs11114203, rs12273277, rs16869287, rs1526390, and rs6856418) using a suggestive threshold (5 × 10–8 < P < 1 × 10–6). They are located in proximity to the genes that encode GRIN2A, SLIT2, AGTR1, PAWR, and TBC1D1, which are involved in cognitive functions and/or psychiatric diseases. We found two novel genetic associations with educational attainment, which largely corresponded to associations with cognitive functions and psychiatric diseases.

Selection signals of Korean cattle might be attributed largely to artificial selection for meat quality. Rapidly increased intragenic markers of newly annotated genes in the bovine genome would help overcome limited findings of genetic markers associated with meat quality at the selection signals in a previous study. The present study examined genetic associations of marbling score (MS) with intragenic nucleotide variants at selection signals of Korean cattle. A total of 39 092 nucleotide variants of 407 Korean cattle were utilized in the association analysis. A total of 129 variants were selected within newly annotated genes in the bovine genome. Their genetic associations were analyzed using the mixed model with random polygenic effects based on identical-by-state genetic relationships among animals in order to control for spurious associations produced by population structure. Genetic associations of MS were found (P<3.88×10-4) with six intragenic nucleotide variants on bovine autosomes 3 (cache domain containing 1, CACHD1), 5 (like-glycosyltransferase, LARGE), 16 (cell division cycle 42 binding protein kinase alpha, CDC42BPA) and 21 (snurportin 1, SNUPN; protein tyrosine phosphatase, non-receptor type 9, PTPN9; chondroitin sulfate proteoglycan 4, CSPG4). In particular, the genetic associations with CDC42BPA and LARGE were confirmed using an independent data set of Korean cattle. The results implied that allele frequencies of functional variants and their proximity variants have been augmented by directional selection for greater MS and remain selection signals in the bovine genome. Further studies of fine mapping would be useful to incorporate favorable alleles in marker-assisted selection for MS of Korean cattle.

Genetic associations of nucleotide sequence variants with carcass traits in beef cattle were investigated using a genome-wide single nucleotide polymorphism (SNP) assay. Three hundred and thirteen Korean cattle were genotyped with the Illumina BovineSNP50 BeadChip, and 39,129 SNPs from 311 animals were analysed for each carcass phenotype after filtering by quality assurance. Five sequence markers were associated with one of the meat quantity or quality traits; rs109593638 on chromosome 3 with marbling score, rs109821175 on chromosome 11 and rs110862496 on chromosome 13 with backfat thickness (BFT), and rs110228023 on chromosome 6 and rs110201414 on chromosome 16 with eye muscle area (EMA) (P < 1.27 × 10(-6) , Bonferonni P < 0.05). The ss96319521 SNP, located within a gene with functions of muscle development, dishevelled homolog 1 (DVL1), would be a desirable candidate marker. Individuals with genotype CC at this gene appeared to have increased both EMA and carcass weight. Fine-mapping would be required to refine each of the five association signals shown in the current study for future application in marker-assisted selection for genetic improvement of beef quality and quantity.

7503 Background: Downstaging via NACRT is a significant prognostic factor for better survival in patients (pts) with NSCLC. Thus, identification of N2 clearing after NACRT is a critical factor for patient selection for thoracotomy. We evaluated the usefulness of FDG- PET in predicting N2 clearing after NACRT and survival after surgical resection in pts with N2 positive NSCLC. Methods: From November 2002 to October 2006, 45 pts with biopsy-proven N2 positive NSCLC were enrolled for NACRT. Thirty-four pts who had FDG-PET data before and after NACRT and underwent surgical resection were analyzed. They received 6 weekly chemotherapy with paclitaxel (50mg/m2)/cisplatin (20mg/m2) and concurrent radiotherapy (1.8Gy/day x 5/week, 45 Gy) during 5 weeks. FDG-PET scan was repeated before and 3 weeks after NACRT. Maximum standardized uptake values (SUVmax) of primary tumor and N2 nodes were measured, and percent changes in SUVmax were calculated. After surgery, the pathology of N2 nodes was assessed. Results: After NACRT, overall mean SUVmax of primary mass and N2 nodes decreased from 7.02±3.68, 6.78±4.18 to 1.80±1.27, 1.52±1.74 (74%, 78% reduction, respectively) and 17/34 pts had metabolic N2 clearing (including 8 false negative) and 17/34 pts had remained positive N2 (including 10 false positive) by FDG-PET. Mean percentage changes of SUVmax of primary mass and N2 nodes in pathologic N2 clearing group (n=19) were 75% and 76% and those with remained N2 group (n=15) were 67% and 78%, with no significant difference between two groups. Median progression-free survival (PFS) and overall survival (OS) of all 34 pts were 38 months and 45 months with median follow-up duration of 34 months (range 9–56). Median PFS in pts who achieved a reduction in SUVmax of N2 nodes of more than 60% and in pts who achieved one of less than 60% were 38 months and 14 months (log-rank test, p=0.044). OS between two groups had no significant difference. Conclusions: FDG-PET before and 3 weeks after NACRT could not predict pathologic N2 clearing. Patients who had a reduction in SUVmax of N2 nodes of more than 60% showed better PFS in patients with NSCLC treated with NACRT followed surgical resection. No significant financial relationships to disclose.

13031 Background: FLT has been developed as a PET tracer for imaging tumor proliferation. We evaluated whether FLT-PET could predict tumor response only after 3 days of gefitinib treatment. Methods: Nonsmokers with adenocarcinoma of the lung were eligible for this study. FLT-PET was performed at 1 day before and 3 days after the start of gefitinib (250 mg/d) therapy. The maximum standardized uptake value (SUVmax) of the main lung mass was measured, and changes in tumor SUVmax were calculated. After 6 weeks of therapy, response was assessed by chest CT according to WHO criteria. The cutoff value predicting subsequent CT response was obtained by receiver operating characteristic curve analysis. Results: Between Jun. 2005 and Nov. 2005, 22 patients were enrolled. CT response was partial response in 12 (54%), stable disease in 5 (23%), and progressive disease in 5 (23%). As early as 3 days after the initiation of therapy, significant difference in % changes of tumor SUVmax on FLT-PET was observed between responders and nonresponders (−32% v −2.3%, P = .002) ( Table ). When a reduction of tumor SUVmax ≥ 20% was used as a cutoff value for FLT-PET response, CT response could be predicted with positive and negative predictive values of 100% and 83%, respectively. Time to progression was significantly longer in FLT-PET responders than nonresponders (median 5.1 v 1.4 months, P = .011). Conclusions: Using FLT-PET obtained on days 0 and 3 of gefitinib therapy, the response could be early predicted in patients with NSCLC. [Table: see text] No significant financial relationships to disclose.

While candidaemia that develops during systemic antifungal prophylaxis or therapy [breakthrough (BT) candidaemia] has been reported increasingly, the risk factors and outcome of BT candidaemia are not yet known definitely. We evaluated a consecutive series of cancer patients with candidaemia at Asan Medical Center during 6 years to identify risk factors and outcome in BT candidaemia comparing with non-BT candidaemia. Fifty-four episodes of candidaemia in cancer patients diagnosed during this period were reviewed retrospectively. There were 10 episodes (18.5%) of BT candidaemia in which the species distribution and frequency of catheter-related infection in the BT and non-BT groups were similar. BT candidaemia had a tendency to occur more frequently in patients with haematological than non-haematological diseases. Profound neutropenia and disseminated candidiasis were more common in the BT group; however, these differences were not statistically significant (P = 0.17 and 0.07 respectively). The duration of prior antibiotic therapy and duration of profound neutropenia (<100 mm(-3)) were identified as risk factors for BT candidaemia (P < 0.01 and 0.02 respectively) in univariate analysis and the latter was the only risk factor in multivariate analysis. The death rates due to candidaemia were 85.7% in the BT group and 42.9% in the non-BT group (P = 0.08); however, BT candidaemia alone did not increase mortality rate.

The isolation of carbapenem-resistant Klebsiella pneumoniae (CRKP) has been increasingly reported. However, no study analyzing potential risk factors for the acquisition of CRKP has been published as of now. We therefore performed a case-control study to determine the risk factors for the acquisition of CRKP. CRKP was nosocomially isolated from 30 patients between January 1997 and August 2003. Control patients were randomly selected at a ratio of 4:1 from the same medical or surgical services from which patients were receiving care when isolation of CRKP occurred. Risk factors for CRKP were previous use of carbapenem (adjusted odds ratio [AOR], 28.68; 95% confidence interval [CI], 9.08-90.55) and cephalosporin (AOR, 4.10; 95% CI, 1.35-12.43). In contrast, previous use of fluoroquinolone was negatively associated with isolation of CRKP (AOR, 0.26; 95% CI 0.07-0.97); however, the possibility of selection bias cannot be ruled out. Our results suggest that the nosocomial isolation of CRKP is strongly favored by the selection pressure of carbapenem.

OBJECTIVESWe investigated the trends of nalidixic acid resistance in human non-typhoid Salmonella enterica in a Korean population, and examined some possible mechanisms involved in this resistance.METHODSA total of 261 clinical strains were tested. For all strains, the MICs of nalidixic acid were determined. Nalidixic acid-resistant strains underwent further analysis, including determination of MICs of other antibiotics, mutation analysis within the topoisomerase genes, organic solvent tolerance test, western blotting for AcrA, marOR mutation analysis, ciprofloxacin accumulation test, and PCR for the qnr gene. The clonal relationships of Salmonella strains were examined by random amplified polymorphic DNA analysis.RESULTSThe incidence of nalidixic acid resistance increased from 1.8% in 1995-96 to 21.8% in 2000-02. The resistance rate was higher in S. enterica serotype Enteritidis (21.6%) than in serotype Typhimurium (12.1%). The nalidixic acid resistance rates in Salmonella Enteritidis varied according to the phage type (PT) and Salmonella Enteritidis PT 1 was most commonly associated with resistance to nalidixic acid. Several cases of clonal spread, especially by Salmonella Enteritidis PT 1, were identified. Of the 46 nalidixic acid-resistant strains, 43 had single mutations in the gyrA gene. Four strains were organic solvent-tolerant and were associated with decreased ciprofloxacin accumulation; three of these showed increased expression of AcrA and had novel mutations in marOR (84L). The qnr gene was not identified.CONCLUSIONSRecently, the rate of nalidixic acid resistance in Korean clinical Salmonella strains markedly increased and it was partly due to the clonal spread of Salmonella Enteritidis, especially PT 1. The main mechanism of nalidixic acid resistance was a mutation in the gyrA region.

Intravenous polyspecific immunoglobulin G (IVIG) has been reported to be efficacious as adjunctive therapy in patients with toxic shock syndrome caused by group A streptococci (GAS). GAS is also an important cause of necrotizing fasciitis, for which an early and extensive surgical intervention is currently advocated. Here we report on the use of an aggressive medical regimen including high-dose IVIG together with a conservative surgical approach in severe GAS soft tissue infection. We describe 7 patients with severe soft tissue infection caused by GAS, who all were treated with effective antimicrobials and high-dose IVIG. Surgery was either not performed or only limited exploration was carried out. Six of the patients had toxic shock syndrome. All patients survived. Immunostaining of tissue biopsies from 2 of the patients revealed high levels of GAS, superantigen and pro-inflammatory cytokines initially, which were dramatically reduced in a repeat biopsy of the initial operative site collected from 1 of the patients 66 h post-IVIG administration. The study suggests that the use of a medical regimen including IVIG in patients with severe GAS soft tissue infections may allow an initial non-operative or minimally invasive approach, which can limit the need to perform immediate wide debridements and amputations in unstable patients.

To characterize the phenotypes and genotypes of erythromycin-resistant clinical isolates of Streptococcus pneumoniae in Korea and to evaluate the in vitro activity of telithromycin against these erythromycin-resistant isolates, we tested a total of 676 isolates of S. pneumoniae collected from 1997 to 2002 in a tertiary hospital in Seoul, Republic of Korea. MICs for erythromycin and telithromycin were determined by the agar dilution method. The macrolide resistance phenotypes of erythromycin-resistant isolates were determined by the erythromycin- clindamycin-rokitamycin triple disk (ECRTD) and MIC induction tests, whereas their macrolide resistance genotypes were determined by PCR for the erm(B), erm(A), subclass erm(TR), and mef genes. To discriminate between mef(A) and mef(E), PCR-restriction fragment length polymorphism (RFLP) analyses were performed. Of the 676 S. pneumoniae isolates, 459 (67.9%) were resistant to erythromycin. Of the 459 erythromycin-resistant isolates, 343 (74.7%) were assigned to the cMLS phenotype, 48 (10.4%) to the iMcLS phenotype, 4 (0.9%) to the iMLS phenotype, and 64 (14.0%) to the M phenotype. The erm(B) gene was detected in 251 (54.6%) isolates, the mef gene was detected in 64 (14.0%), and both the erm(B) and mef genes were detected in 144 (31.4%) isolates. All of the mef genes detected were identified as mef(E). Of the 459 erythromycin- resistant isolates, all but one were susceptible to telithromycin. The MIC(50)/MIC(90) to telithromycin of isolates carrying erm(B), mef(E), and both genes was 0.06/0.5 microg/ml, 0.03/0.125 microg/ml, and 0.5/1.0 microg/ml, respectively. Although the MICs of telithromycin for the erythromycin-resistant isolates varied according to genotype, telithromycin was very active against these erythromycin-resistant S. pneumoniae.

Journal of Pediatric Gastroenterology and NutritionVolume 39, Issue S1 p. S160-S160 ABSTRACTS: Poster Session Abstracts P0269 HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS PRESENTING AS SEVERE ACUTE LIVER DYSFUNCTION J. Ryu, J. Ryu Pediatrics, Asan Medical Center, Seoul, South KoreaSearch for more papers by this authorS. Chang, S. Chang Pediatrics, Asan Medical Center, Seoul, South KoreaSearch for more papers by this authorK. Kim, K. Kim Pediatrics, Asan Medical Center, Seoul, South KoreaSearch for more papers by this authorM. Lee, M. Lee Pediatrics, Asan Medical Center, Seoul, South KoreaSearch for more papers by this authorJ. Seo, J. Seo Pediatrics, Asan Medical Center, Seoul, South KoreaSearch for more papers by this authorH. Moon, H. Moon Pediatrics, Asan Medical Center, Seoul, South KoreaSearch for more papers by this authorT. Ghim, T. Ghim Pediatrics, Asan Medical Center, Seoul, South KoreaSearch for more papers by this authorH. Chi, H. Chi Laboratory Medicine, Asan Medical Center, Seoul, South KoreaSearch for more papers by this author J. Ryu, J. Ryu Pediatrics, Asan Medical Center, Seoul, South KoreaSearch for more papers by this authorS. Chang, S. Chang Pediatrics, Asan Medical Center, Seoul, South KoreaSearch for more papers by this authorK. Kim, K. Kim Pediatrics, Asan Medical Center, Seoul, South KoreaSearch for more papers by this authorM. Lee, M. Lee Pediatrics, Asan Medical Center, Seoul, South KoreaSearch for more papers by this authorJ. Seo, J. Seo Pediatrics, Asan Medical Center, Seoul, South KoreaSearch for more papers by this authorH. Moon, H. Moon Pediatrics, Asan Medical Center, Seoul, South KoreaSearch for more papers by this authorT. Ghim, T. Ghim Pediatrics, Asan Medical Center, Seoul, South KoreaSearch for more papers by this authorH. Chi, H. Chi Laboratory Medicine, Asan Medical Center, Seoul, South KoreaSearch for more papers by this author First published: 01 June 2004 https://doi.org/10.1002/j.1536-4801.2004.tb12699.x Submitted by: [email protected] Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume39, IssueS1June 2004Pages S160-S160 RelatedInformation

Two hundred and forty-nine patients with monomicrobial bacteraemia due to third-generation cephalosporin (TGC)-resistant Citrobacter freundii (42), E. aerogenes (23), E. cloacae (143), and Serratia marcescens (41) were analyzed for antibiotic therapy used and outcome. For isolates with resistance to any of the TGCs, all β-lactams, except imipenem, were considered ineffective. Of 152 patients given appropriate treatment, the mortality rates were 10.9% for 128 patients given monotherapy and 25.0% for 24 patients given combination therapy (P=0.09). Of patients given monotherapy, there were no significant differences in mortality between imipenem, aminoglycoside, and ciprofloxacin treatment groups (P=0.57). Only shock was associated with mortality in multivariate analysis. In conclusion, for patients with TGC-resistant Gram-negative bacteraemia, no significant difference in outcome was observed between single antibiotic therapy groups or monotherapy and combination therapy groups.

Background: This studywas performed to characterize the clinical features and toidentify the risk factors for resistance to extended-spectrumcephalosporins (ESCs) and for mortality in patients withCitrobacter freundiibacteremia.

The clinical significance and virulence potential of Enterococcus casseliflavus/flavescens and Enterococcus gallinarum are still uncertain. We retrospectively analyzed 56 cases of significant bacteremia caused by E. casseliflavus or E. gallinarum. Of these cases, 25 (44.6%) were associated with polymicrobial bacteremia, and 43 (76.8%) were associated with entry via the biliary tract. Resistance to vancomycin was observed in 17 (30.4%) of these 56 patients, and this resistance was significantly associated with E. gallinarum bacteremia (adjusted odds ratio [AOR], 10.56; 95% confidence interval [CI], 2.41-46.27) and bacteremia without biliary tract origin (AOR, 6.74; 95% CI, 1.44-31.67). The crude mortality rate was 13%, and the bacteremia-related mortality rate was 1.9%. In conclusion, bacteremia due to E. casseliflavus and E. gallinarum is commonly associated with biliary tract disease and may be associated with a low risk of mortality.

This study was performed to determine the incidence and serogroups of meningococcal disease in the Korean Army. From August 2000 to July 2001, we identified prospective cases in the Korean Army. Meningococcal disease was confirmed by isolation of Neisseria meningitidis or detection of its antigen by latex agglutination from cerebrospinal fluid (CSF) or blood. Polymerase chain reactions (PCRs) were performed in the crgA gene to identify N. meningitidis regardless of its serogroup, and then in orf-2 (serogroup A) and siaD (serogroups B, C, Y, and W135) respectively for serogroup prediction. During the study period, twelve patients (four meningitis and eight septicaemia) were identified. The annual incidence was 2.2 per 100,000 (95% confidence interval, 1.3-3.8) among 550,000 private soldiers. Latex agglutinations were positive to A/C/Y/W135 polyvalent latex, but not to B latex in all patients. PCRs of crgA gene were positive in ten patients, whose samples (2 isolates from CSF, 2 CSFs, and 6 sera) were stored. In PCRs for serogroup prediction, one isolate was serogroup A, and one isolate and two sera were serogroup C. The need for meningococcal vaccination would be considered in the Korean Army through the cost-benefit analysis based on the result of this study.

From 1991 to 2000, 125 sporadic cases of Klebsiella oxytoca bacteremia were analyzed retrospectively to review clinical features and to identify the risk factors associated with resistance to extended-spectrum cephalosporins and fatal outcome. Bacteremia was acquired nosocomially in 52% of the patients. Almost all patients (97%) had an underlying disease, with biliary and pancreatic disease occurring most frequently (55%). The biliary tract was the most common site of infection (44%). Resistance to extended-spectrum cephalosporins was identified in 22 of the 125 (18%) Klebsiella oxytoca blood isolates and resistance to ciprofloxacin in 9 (7%). Only previous antibiotic therapy was strongly associated with resistance to extended-spectrum cephalosporins in patients with Klebsiella oxytoca bacteremia (P=0.009). The mortality rate was 24% and was higher in patients infected with isolates resistant to extended-spectrum cephalosporins (41% vs. 20%; P=0.04). In multivariate analysis, fatal outcome was independently associated with septic shock, deteriorated mental status, polymicrobial bacteremia, and solid tumor. Surgical therapy had a protective effect (OR, 0.06; 95% CI, 0.005–0.7; P=0.03). In conclusion, Klebsiella oxytoca bacteremia was most commonly associated with biliary tract infection. Previous antibiotic therapy was strongly associated with resistance to extended-spectrum cephalosporins in patients with Klebsiella oxytoca bacteremia.

To identify the clinical implications of extended-spectrum beta-lactamase (ESBL) production, 162 cases of Klebsiella pneumoniae bacteraemia in 154 adults were analysed. Of these cases, 44 (27.2%) were ESBL-producing (ESBLKP). Common sources of ESBLKP bacteraemia included primary bacteraemia (34.1%) and biliary infection (29.5%). The placement of a biliary drainage catheter, nosocomial acquisition, and prior antibiotic therapy were independently associated with ESBL production in multivariate analysis. More cases of ESBLKP than non-ESBLKP received inappropriate antibiotic therapy before culture results were reported (54.5 vs. 3.4%; P = 0.001). In 19 cases of ESBLKP, no significant difference in mortality was observed between patients who received appropriate empiric antibiotic therapy and those who did not (26.3 vs. 20.8%; P = 0.67). The mean length of hospital stay after the onset of bacteraemia was longer in the cases of ESBLKP than in the cases of non-ESBLKP (39.6 vs. 23.9 days; P = 0.008). Directly related mortality was not significantly different between the cases of ESBLKP and the cases of non-ESBLKP (23.3 vs. 20.0%; P = 0.65). None of the patients with biliary infection due to ESBLKP died (0/12; P = 0.03). In conclusion, ESBL production was not significantly associated with death but it had a considerable impact on patients with K. pneumoniae bacteraemia.