PURPOSE: The purposes of this study are to evaluate clinical characteristics of malnourished patients who received nutritional therapy and to compare their clinical courses according to nutritional support team (NST) consultation in tertiary referral hospital in Korea. METHODS: From June 2014 to May 2015, 43,954 admitted patients who were more than 18 years old were retrospectively investigated. Characteristics of patients who received enteral nutrition (EN) or parenteral nutrition (PN) for more than 3 days (nutritional therapy group) were compared to the patients without nutritional therapy (control group). In addition, clinical courses according to NST consultation (NST group and non-NST group) were compared through propensity score matching (PSM). RESULTS: EN or PN was applied in 4,599 patients for more than 3 days (nutritional therapy group: 10.5%). For characteristics, there were significant differences between two groups (nutritional therapy group vs. control group) with age, male proportion, body weight, body mass index. All laboratory data at admission were significantly worse in nutritional therapy group. And for clinical courses, there were significant differences in length of stay (LOS), rate of intensive care unit (ICU) admission, LOS in ICU, Acute Physiology and Chronic Health Enquiry (APACHE II) score, days of nutritional therapy, mortality rate. NST consultation was made in 39% of nutritional therapy group. Among departments, Thoracic Surgery showed the highest rate of NST consultation (68.5%) otherwise Neurosurgery showed the lowest rate (18.7%). When PSM between NST group vs. non-NST group were made, significant differences was shown only in the rate of ICU admission, EN or PN support days, cholesterol at discharge. CONCLUSION: In tertiary referral hospital in Korea, more than 10% of patients still needed active nutritional therapy. NST consultation rate varies among departments. We failed to find significant differences between NST group and non-NST group.
Body Mass Index ; Body Weight ; Cholesterol ; Enteral Nutrition ; Humans ; Intensive Care Units ; Korea* ; Length of Stay ; Male ; Mortality ; Neurosurgery ; Nutrition Therapy ; Nutritional Support ; Parenteral Nutrition* ; Physiology ; Propensity Score ; Retrospective Studies ; Tertiary Care Centers* ; Thoracic Surgery ; Treatment Outcome

BACKGROUND AND PURPOSE: The positive effects of galantamine on cognition and activities of daily living (ADL) in Alzheimer's disease (AD) are thought to be mediated via improvements in attention. The purpose of this study was to determine the effect of galantamine on attention in AD patients using a computerized attention test and to elucidate the relationship between improvements in attention and change in cognition and ADL. METHODS: In this multicenter, open-label, prospective study, patients with mild to moderate AD received galantamine and then submitted to computerized attention tests, the Alzheimer's Disease Assessment Scale-cognitive subscale, and instrumental ADL (IADL) at baseline, 4 weeks, and 12 weeks. The differences in reaction time on computerized tests were explored relative to the changes in cognition and IADL. RESULTS: After 12 weeks of taking the trial medication there was a significant reduction from baseline levels in the choice reaction time (baseline, 5,216+/-3,650 sec; 12 weeks, 4,139+/-2,920 sec; p<0.01) and the simple reaction time (baseline, 1,089+/-782 sec; 12 weeks, 908+/-606 sec; p<0.01). Correlation analyses of changes in choice or simple reaction times relative to cognition and ADL measures yielded no significant associations. The improvement in attention observed at 4 weeks of galantamine treatment was not associated with any significant changes in outcome measures at the end of trial. CONCLUSIONS: This study found no significant association between the improvement in attention after treatment with galantamine and changes in cognition and ADL in patients with mild to moderate AD, despite the significant improvement in attention over the course of the treatment.
Activities of Daily Living* ; Alzheimer Disease* ; Cognition* ; Galantamine* ; Humans ; Outcome Assessment (Health Care) ; Prospective Studies ; Reaction Time

V. vulnificus is an estuarine bacterium which causes septicemia and shock in susceptible patients. The organism produces a hemolytic cytolysin (VvH), which has a membrane damaging effect on erythrocytes. To clarify the mechanisms by which VvH might contribute to virulence, we examined its effect on macrophages. When mouse peritoneal macrophages were harvested and co-cultured with hemolysin-positive V. vulnificus strains (100 bacteria/ cell), about 60% of the macrophages were killed; macrophages were not killed when co-cultured V. vulnificus strain CVD 707, a VvH-negative deletion mutant. Exposure of macrophages to filtered culture supernatants (2.5 HU/ml) and purified VvH (3 HU/ml) resulted in an increase in dead cells (80 and 90%, respectively), as determined by the trypan blue dye exclusion method and LDH release from macrophages was also increased (70 and 65.5%, respectively). The cytotoxic effect of VvH on macrophages was both the dose- and time-dependent. The VvH caused damage to the macrophage membrane and was blocked significantly by preincubation with cholesterol (p<0.01). Fetal bovine serum showed remarkable inhibition of VvH synthesis by V. vulnificus and inhibited VvH activity in culture supernatant. Cell viability was increased by 35% (p<0.01) and LDH release decreased by 28% (P<0.01) when macrophages were incubated with V. vulnificus (100 bacteria/ cell) in DMEM-10% FBS for 2 hr. Bacterial clearance activity of mice against V. vulnificus CVD 707 was decreased by pretreatment with 10 HU of VvH. This result suggests that the VvH can impair the membrane of macrophages and may play a role in the pathogenesis of V. vulnificus septicemia.
Animals ; Cell Survival ; Cholesterol ; Erythrocytes ; Humans ; Macrophages ; Macrophages, Peritoneal* ; Membranes ; Mice* ; Perforin ; Sepsis ; Shock ; Trypan Blue ; Vibrio vulnificus* ; Vibrio* ; Virulence

The tyrosine-protein kinase Tec (TEC) is a member of non-receptor tyrosine kinases and has critical roles in cell signaling transmission, calcium mobilization, gene expression, and transformation. TEC is also involved in various immune responses, such as mast cell activation. Therefore, we hypothesized that TEC polymorphisms might be involved in aspirin-exacerbated respiratory disease (AERD) pathogenesis. We genotyped 38 TEC single nucleotide polymorphisms in a total of 592 subjects, which comprised 163 AERD cases and 429 aspirin-tolerant asthma controls. Logistic regression analysis was performed to examine the associations between TEC polymorphisms and the risk of AERD in a Korean population. The results revealed that TEC polymorphisms and major haplotypes were not associated with the risk of AERD. In another regression analysis for the fall rate of forced expiratory volume in 1 second (FEV1) by aspirin provocation, two variations (rs7664091 and rs12500534) and one haplotype (TEC_BL2_ht4) showed nominal associations with FEV1 decline (p = 0.03-0.04). However, the association signals were not retained after performing corrections for multiple testing. Despite TEC playing an important role in immune responses, the results from the present study suggest that TEC polymorphisms do not affect AERD susceptibility. Findings from the present study might contribute to the genetic etiology of AERD pathogenesis.
Aspirin ; Asthma ; Calcium ; Forced Expiratory Volume ; Gene Expression ; Haplotypes ; Logistic Models ; Mast Cells ; Phosphotransferases ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Tyrosine

PURPOSE: The human WD repeat-containing protein 46 (WDR46; also known as C6orf11), located at the disease-relevant centromere side of the class II major histocompatibility complex region, is hypothesized to be associated with risk of aspirin-exacerbated respiratory disease (AERD) as well as a decline in forced expiratory volume in the first second (FEV1), an important diagnostic marker of asthma. METHODS: To investigate the association between WDR46 and AERD, five single-nucleotide polymorphisms (SNPs) were genotyped in 93 AERD cases and 96 aspirin-tolerant asthma controls of Korean ethnicity. Three major haplotypes were inferred from pairwise comparison of the SNPs, and one was included in the association analysis. Differences in the frequency distribution of WDR46 SNPs and haplotype were analyzed using logistic and regression models via various modes of genetic inheritance. RESULTS: Depending on the genetic model, the logistic and regression analyses revealed significant associations between rs463260, rs446735, rs455567, rs469064, and WDR46_ht2 and the risk of AERD (P=0.007-0.04, Pcorr=0.01-0.04) and FEV1 decline after aspirin provocation (P=0.006-0.03, Pcorr=0.01-0.03). Furthermore, functional analysis in silico showed that the G>A allele of rs463260 located in the 5' untranslated region potentially matched a nucleotide sequence within an upstream open reading frame of WDR46. CONCLUSIONS: These findings show for the first time that WDR46 is an important genetic marker of aspirin-induced airway inflammation and may be useful for formulating new disease-management strategies.
5' Untranslated Regions ; Alleles ; Aspirin ; Asthma ; Base Sequence ; Centromere ; Computer Simulation ; Forced Expiratory Volume ; Genetic Markers ; Haplotypes ; Humans ; Inflammation ; Major Histocompatibility Complex ; Models, Genetic ; Open Reading Frames ; Polymorphism, Single Nucleotide ; Risk Factors

This study was undertaken to evaluate the present status of intestinal helminthic infections in Koreans, from April 1967 through May 1969. The nationwidely collected stool specimens and scotch-tape anal swabs from primary schoolchildren, middle school students, draftees to army recruitment camp, soldiers and inhabitants of various parts of Korea were examined. The methods employed were Kato's cellophane thick smear technique and formalin-ether sedimentation technique in 40,581 for the prevalence rate of various intestinal helminths, scotch-tape anal swab technique in 8,585 for the prevalence rate of Enterobius vermicularis and by Stoll's dilution egg counting technique in 1,174 for the evaluation of the worm burden of some helminths. The results are as follows. Result of stool examination: The positive rate of intesinal helminthes of any kind was 90.5% among 40,581. In rural people, it was 92.3% in average in contrast to 85.0% in Seoul inhabitants. The infection rate of A. lumbricoides in 40,581 was 58.2%. It was higher in rural people 62.9% than in Seoul inhabitants and highest in 5-9 year-old group by age. The infection of Trichocephalus trichiurus showed the highest prevalence rate in Koreans and it was 74.5%. No remarkable difference was observed between Seoul inhabitants(72.2%) and rural people(75.2%). The tendency of higher prevalence rate with the older age group was observed. The infection rates of hookworm and Trichostrongylus orientalis in 40,581 examinations by cellophane thick smear were 5.1% and 5.8% respectively. But in 4,949 examinations for which refined cellophane thick smear technique and formalin-ether sedimentation technique were employed, the infection rates were turned out 17.6% in hookworm and 15.9% in T. orientalis. Although rural people showed higher infection rate of hookworm(18.8%) than Seoul inhabitants(13.8%), the reverse was true in T. orientalis infection rate(14.5% : 20.3%). Both kinds of infections were tend to be higher with the increase of age. The infection rates of Clonorchis sinensis and Metagonimus yokogawai were 4.7% and 0.4% respectively. In both kinds of infections male showed higher infection rates than female and the tendencies of higher infection rate in the older age group were observed. The provinces which showed the higher infection rate of C. sinensis were South and North Kyongsang Do and North Cholla Do, all of which are provinces of southern part of Korea. Some endemic foci of M. yokogawai were noticed in South Kyongsang Do and South Cholla Do. The infection rate of Taenia spp. by applying only the stool examination was 0.7% throughout the survey. No sex difference in infection rate of Taenia spp. was noticed, but in older age group it was increased. Cheju Do, the island of extreme southern part of Korea seemed the most endemic area and South and North Cholla Do were next in ranking of Taenia infection rate. The ova of Hymenolepis nana were observed in 0.2% and all of them were under the age of 20 except only one caes. The infection rate seemed higher in female (0.3%: 0.1%). No geographical difference was noticed except 1.1% of schoolchilderen and students of Cheju Do. Result of Scotch-tape anal swab technique for E. vermicularis infection. The infection rate of E. vermicularis in 8,585 urban and rural schoolchildren and rural inhabitants was 46.6%. Female (57.9%) had definitely higher infection rate than male (41.4%). The infection rate was significantly higher in rural people than Seoul schoolchildren. The exteme example was 79.7% in schoolchildren of South Cholla Do. Result of worm burden examination by Stoll's dilution egg-counting technique: Among 1,174 examinations, countable(E.P.G.> 100) cases of A. lumbricoides were 745(63.5%) and the mean E.P.G. was 9,723. The mean E.P.G. in Seoul inhabitants was 5,835 in contrast to 10,820 in rural people. The age group of 5-9 showed the heaviest mean E.P.G., 11,337. 70.6% of 745 cases were less than 10,000 in E.P.G. which means light infection. Countable cases by Stoll's technique for T. trichiurus ova were 63.5% and mean E.P.G. was 649. No difference between Seoul and rural inhabitants was observed. Grade I and II in which E.P.G. is less than 5,000 involve 99.3% of positive cases. 91 cases (7.9%) in 1,174 were positive for hookworm ova by Stoll's technique and mean E.P.G. was 501. All cases were in Grade I and II which were less than 5,000 in E.P.G. Trichostrongylus orientalis was positive only in 25 cases (2.1%) by Stoll's technique and mean E.P.G. was 340. No cases were found to have more than 5,000 in T. orientalis E.P.G. The mean E.P.G. of Clonorchis sinensis among the referred cases of clonorchiasis to Department of Parasitology, Seoul National University, was 9,416. On the other hand mean E.P.G. of C. sinensis was 21,376 among cases in the hyperendemic area of Kimhae, South Kyongsang Do, and 3,073 in cases from other various localities. Among referred clonorchiasis cases to our Department, 21.6% were turned out to have the E.P.G. more than 10,000. The cases who have the E.P.G. more than 10,000 in hyperendemic area, Kimhae were 40.7% and in other various localities were 9.1%
parasitology-helminth-nematoda-trematoda-cestoda ; epidemiology ; Ascaris lumbricoides ; Trichocephalus trichiurus ; Trichostrongylus orientalis ; Clonorchis sinensis ; Metagonimus yokogawai ; Taenia sp. ; Hymenolepis nana ; Enterobius vermicularis

Purpose: We performed this study to determine whether the degree of neutropenia after the first chemotherapy cycle can be used as a surrogate marker of individual susceptibility to chemotherapeutic agents affecting treatment outcome in patients with neuroblastoma. Materials and Methods: The study included 313 patients who received the first cycle chemotherapy with a CEDC (cisplatin+etoposide+doxorubicin+cyclophosphamide) regimen and had absolute neutrophil count (ANC) data available. The cumulative incidences of progression and treatment-related mortality (TRM) were estimated. To identify genetic variations associated with the ANC, a genome-wide association study (GWAS) was performed. Results: An ANC of 32.5/μL was determined as the cutoff point to categorize patients into the good and poor prognosis subgroups in terms of progression. Patients with a high nadir ANC had a higher cumulative incidence of progression than those with a low nadir ANC (p < 0.001). In multivariate analysis, high nadir ANC, age, bone marrow involvement, and unfavorable histology were poor prognostic factors. With regard to the TRM, patients with a low nadir ANC (ANC < 51.0/μL) had a higher cumulative incidence of TRM than those with a high nadir ANC (p=0.010). In GWAS, single-nucleotide polymorphisms of LPHN2 and CRHR1 were significantly associated with the nadir ANC. Conclusion In neuroblastoma patients, the degree of neutropenia after the first chemotherapy cycle can be used as a surrogate marker to predict an individual’s susceptibility to chemotherapeutic agents. Tailoring of treatment based on the degree of neutropenia needs to be considered.

Purpose: Neuroblastoma (NB) is the most common extracranial solid tumor found in children. To identify significant genetic factors for the risk of NB, several genetic studies was conducted mainly for Caucasians and Europeans. However, considering racial differences, there is a possibility that genetic predispositions that contribute to the development of NB are different, and GWAS study has not yet been conducted on Korean NB patients. Materials and Methods: To identify the genetic variations associated with the risk of pediatric NB in Korean children, we performed a genome-wide association analysis with 296 NB patients and 1000 unaffected controls (total n = 1,296) after data cleaning and filtering as well as imputation of non-genotyped SNPs using IMPUTE v2.3.2. Results: After adjusting for multiple comparisons, we found 21 statistically significant SNPs associated with the risk of NB (Pcorr < 0.05) within 12 genes (RPTN, MRPS18B, LRRC45, KANSL1L, ARHGEF40, IL15RA, L1TD1, ANO7, LAMA5, OR7G2, SALL4, and NEUROG2). Interestingly, out of these, 12 markers were nonsynonymous SNPs. The SNP rs76015112 was most significantly associated with the risk of NB (p = 8.1E-23, Pcorr = 2.3E-17) and was located in the RPTN gene. In addition, significant nonsynonymous SNPs in ADGRE1 were found in patients with MYCN amplification (rs7256147, p = 2.6E-05). In high-risk group, rs7256147 was observed as a significant SNP (p = 5.9E-06). Conclusion Our findings might facilitate improved understanding of the mechanism of pediatric NB pathogenesis. However, functional evaluation and replication of these results in other populations are still needed.

BACKGROUND: Hemopoiesis and erythropoiesis have been studied mainly in immortalized cell lines and semisolid medium. But cell lines do not represent normal erythropoiesis, besides, in semisolid medium the cells are immobilized that it is difficult to do additional immunologic, biochemical, and molecular biologic experiments. In the present study we used a two-phase liquid culture system to isolate and quantify erythroid progenitors from peripheral blood and cord blood. METHODS: Peripheral and cord blood were obtained from three healthy donors and three full-term deliveries, respectively. Mononuclear cells were separated by density gradient centrifugation and were cultured in the first phase at a density of 5x106/mL in alpha- minimal essential medium ( -MEM). After 5~7 days of incubation at 37degrees C in an atmosphere of 5% CO2 with extra humidity, the nonadherent cells were harvested and recultured in the original volume of -MEM containing 10ng/mL stem cell factor and 1U/mL erythropoietin (EPO). Cellular morphology was observed by preparing cytocentrifuge slides stained with Wright Giemsa. On days 8, 10, 12, and 16 of the second phase, hemoglobin (Hb)- containing cells were counted on hemocytometer after staining with acid benzidine and glycophorin A-positive erythroid cells were scored by a flow cytometer. RESULTS: Pronormoblasts first started to appear on days 4~5 in the secondary culture. On day 10 basophilic normoblasts could be seen and on days 12~14 orthochromatic normoblasts were present. Both from peripheral and cord blood the maximum number of benzidine and glycophorin A-positive cells were achieved after 10 days and the total erythroid cell yield was approximately 1x106/mL. CONCLUSION: Using two-phase liquid culture, erythroid cell yield reached 1x106/mL both from peripheral and cord blood. In addition, this culture system permits the study of the effect of various culture conditions and components without terminating the culture, therefore it might provide us a useful experimental tool for studying pathogenesis and therapeutic modalities in genetic erythroid disorders as well as erythroid cell development.
Atmosphere ; Basophils ; Cell Line ; Centrifugation, Density Gradient ; Erythroblasts ; Erythroid Cells ; Erythropoiesis ; Erythropoietin ; Fetal Blood ; Glycophorin ; Humans ; Humidity ; Stem Cell Factor ; Tissue Donors

Integrins are transmembrane receptor proteins that mediate cell-cell adhesion and cell-extracellular matrix (ECM) adhesion. The deregulation of cell-ECM adhesion and the abnormal expression of beta1 (beta1) integrins (ITGB1s) are involved in tumor development and metastasis. In the liver, the expression of integrins and ECM proteins can be a cause of hepatocellular carcinoma (HCC) development. We performed direct DNA sequencing of 24 individuals, and identified 23 sequence variants of ITGB1 polymorphisms. Among these 23 variants, 7 common variants were selected based on frequencies and linkage disequilibrium, and then genotyped in a larger-scale group of subjects (n=1,103). The genetic associations of ITGB1 polymorphisms with the clearance of HBV and HCC outcome of HBV patients were analyzed using logistic regression models and Cox relative hazard models. Although there was no significant association observed between the polymorphisms and the HCC outcome of HBV patients, the second most common haplotype (ITGB1 haplotype-2 [C-C-C-C-T-C-T]) was putatively associated with HBV clearance (OR=0.75, p=0.008 and P(corr)=0.05). The minor allele frequency (MAF) of ITGB1 haplotype-2 of the spontaneously recovered (SR) group was significantly higher than that of the chronic carrier group (CC) (freq. = 0.248 vs. 0.199). The information derived from this study could be valuable for understanding the genetic factors involved in the clearance of HBV.
Carcinoma, Hepatocellular ; Gene Frequency ; Haplotypes ; Humans ; Integrins ; Linkage Disequilibrium ; Liver ; Logistic Models ; Neoplasm Metastasis ; Proportional Hazards Models ; Proteins ; Sequence Analysis, DNA