[Show abstract][Hide abstract] ABSTRACT: Objective:
Biological markers for Alzheimer's disease (AD) will help clinicians make objective diagnoses early during the course of dementia. Previous studies have suggested that cell cycle dysregulation begins earlier than the onset of clinical manifestations in AD.
We examined the lymphocyte expression of cell cycle proteins in AD patients, dementia controls (DC), and normal controls (NC). One-hundred seventeen subjects (36 AD, 31 DC, and 50 NC) were recruited. The cell cycle proteins CDK2, CDK4, CDK6, cyclin B, and cyclin D were measured in peripheral lymphocytes. Cell cycle protein expression in the three groups was compared after adjusting for age and sex.
The levels of cell cycle proteins CDK2, CDK4, CDK6, cyclin B, and cyclin D were significantly higher in AD patients than in the NC subjects. The DC group manifested intermediate levels of cell cycle proteins compared with the AD patients and the NC subjects. The present study indicates that cell cycle proteins are upregulated in the peripheral lymphocytes of AD patients.
Cell cycle dysregulation in peripheral lymphocytes may present a promising starting point for identifying peripheral biomarkers of AD.
Preview · Article · Jan 2016 · Psychiatry investigation
[Show abstract][Hide abstract] ABSTRACT: Objective To report the nationwide prevalence of dizziness and vestibular dysfunction in the Korean population and determine the associated factors.
Design Cross-sectional analysis of a nationwide health survey.
Methods We obtained data from the 2009 to 2010 Korea National Health and Nutrition Examination Surveys, which were cross-sectional surveys of the South Korean civilian, non-institutionalised population aged 40 years and older (N=3267). A field survey team performed interviews and physical examinations. Structured questionnaires were handed out and balance function tests using the modified Romberg test of standing balance on firm and compliant support surfaces were performed on participants. Failure on the modified Romberg test was regarded to indicate vestibular dysfunction.
Results The prevalence of dizziness during the past year was 16.70% (95% CI 14.65% to 18.76%). The presence of vestibular dysfunction was noted in 1.84% (95% CI 1.18% to 2.51%). In addition, the prevalence of experiencing falls and positional dizziness were 1.46% (95% CI 0.87% to 2.06%) and 1.73% (95% CI 1.17% to 2.29%), respectively. Multivariable analysis revealed that dizziness was associated with increased age, female gender, hearing loss and stress. Vestibular dysfunction was associated with increased age, history of dizziness and hearing loss.
Conclusions Vertigo and dizziness are the greatest contributors to the burden of disability in the aged population. Screening for dizziness and vestibular dysfunction, and management of associated factors might be important for improving compromised quality of life due to postural imbalance caused by vestibular problems.
[Show abstract][Hide abstract] ABSTRACT: Background:
Improving gastric accommodation and gastric emptying is an attractive physiological treatment target in patients with functional dyspepsia (FD). We evaluated the effect of DA-9701, a new drug for FD, on gastric motor function after a meal in healthy volunteers using magnetic resonance imaging (MRI).
Forty healthy volunteers were randomly allocated to receive either DA-9701 or placebo. After 5 days of treatment, subjects underwent gastric MRI (60 min before and 15, 30, 45, 60, 90, and 120 min after a liquid test meal). Gastric volume was measured through 3-dimensional reconstruction from MRI data. We analyzed 4 outcome variables including changes in total gastric volume (TGV), proximal TGV, and proximal to distal TGV ratio after a meal and gastric emptying rates after adjusting values at the pre-test meal.
Changes in TGV and proximal TGV after a meal did not differ between the DA-9701 and placebo groups (difference between groups -25.9 mL, 95% confidence interval [CI] -54.0 to 2.3 mL, P = 0.070 and -2.9 mL, 95% CI -30.3 to 24.5 mL, P = 0.832, respectively). However, pre-treatment with DA-9701 increased postprandial proximal to distal TGV ratio more than placebo (difference between groups 0.93, 95% CI 0.08 to 1.79, P = 0.034). In addition, pre-treatment with DA-9701 significantly increased gastric emptying as compared with placebo (mean difference between groups 3.41%, 95% CI 0.54% to 6.29%, P = 0.021, by mixed model for repeated measures).
Our results suggested that DA-9701 enhances gastric emptying and does not significantly affect gastric accommodation in healthy volunteers. Further studies to confirm whether DA-9701 enhances these gastric motor functions in patients with FD are warranted.
[Show abstract][Hide abstract] ABSTRACT: We conducted a 3-stage genome-wide association study (GWAS) of response to antidepressant drugs in an ethnically homogeneous sample of Korean patients in untreated episodes of nonpsychotic unipolar depression, mostly of mature onset. Strict quality control was maintained in case selection, diagnosis, verification of adherence, and outcome assessments. Analyzed cases completed 6 weeks of treatment with adequate plasma drug concentrations. The overall successful completion rate was 85.5%. Four candidate single nucleotide polymorphisms (SNPs) on 3 chromosomes were identified by genome wide search in the discovery sample of 481 patients who received one of four allowed selective serotonin reuptake inhibitor (SSRI) antidepressant drugs (Stage 1). In a focused replication study of 230 SSRI-treated patients, 2 of these 4 SNP candidates were confirmed (Stage 2). Analysis of the Stage 1 and Stage 2 samples combined (n = 711) revealed GWAS significance (P = 1.60×10-8) for these two SNP candidates, which were in perfect linkage disequilibrium. These 2 significant SNPs were confirmed also in a focused cross-replication study of 159 patients treated with the non-SSRI antidepressant drug mirtazapine (Stage 3). Analysis of the Stage 1, Stage 2, and Stage 3 samples combined (n = 870) also revealed GWAS significance for these 2 SNPs, which was sustained after controlling on gender, age, number of previous episodes, age at onset and baseline severity (P = 3.57×10-8). For each SNP, the response rate decreased (odds ratio = 0.31, 95% confidence interval: 0.20 – 0.47) as a function of the number of minor alleles (non-response alleles). The 2 SNPs significantly associated with antidepressant response are rs7785360 and rs12698828 of the AUTS2 gene, located on chromosome 7 in 7q11.22. This gene has multiple known linkages to human psychological functions and neurobehavioral disorders. Rigorous replication efforts in other ethnic populations are recommended.
[Show abstract][Hide abstract] ABSTRACT: The pathogenesis and clinicopathologic characteristics of Epstein-Barr virus (EBV)-negative lymphoepithelioma-like gastric carcinoma (LELC) are still unclear. In addition, it remains controversial whether EBV infection itself affects the prognosis of LELC.
Between 1995 and 2011, 145 LELC patients (124 patients with EBV infection and 21 patients without EBV infection) underwent radical gastrectomy with D2 lymph node dissection. The clinicopathologic features and prognosis of EBV-negative LELC cases were compared with those of EBV-positive LELC cases. The median duration of follow-up after surgery was 55 months. Microsatellite instability (MSI) analysis was performed on 20 EBV-negative LELC cases.
EBV-negative LELC accounted for 14.5 % of the total LELC cases. EBV-negative LELC was significantly associated with older age, female sex, advanced T stage, and advanced American Joint Committee on Cancer (AJCC) tumor stage compared with EBV-positive LELC. In univariate analysis, patients with EBV-negative LELC had significantly shorter overall, disease-specific, and recurrence-free survival than those with EBV-positive LELC. The 5-year overall survival rates were 81.0 % for patients with EBV-negative LELC and 96.2 % for patients with EBV-positive LELC. In a Cox proportional hazards model, EBV infection, age, and AJCC tumor stage were identified as independent predictors of overall survival. MSI-high, MSI-low, and microsatellite-stable tumors accounted for 25, 10, and 65 % of EBV-negative LELC cases, respectively. MSI status did not affect the prognosis of EBV-negative LELC cases.
EBV infection serves as an independent predictor of survival in patients with LELC. EBV-negative LELC exhibited clinicopathologic features and prognosis distinct from those of EBV-positive LELC.
[Show abstract][Hide abstract] ABSTRACT: To investigate clinical effects of equine-assisted activities and therapy (EAA/T) for treating attention-deficit/hyperactivity disorder (ADHD) in children age 6-13 years.
This 12-week, prospective, open-label trial included 24 sessions of EAA/T. Twenty participants (19 boys and 1 girl) completed 12 weeks of EAA/T. Various clinical tests were administered at baseline and after EAA/T. Assessments included the investigator-administered ADHD-Rating Scale (ARS-I), Clinical Global Impressions (CGI)-Severity Scale, Clinical Global Impressions-Improvement Scale (CGI-I), Gordon Diagnostic System, Korea-Child Behavior Checklist (K-CBCL), Self-Esteem Scale, second edition of the Bruininks-Oseretsky test of motor proficiency (BOT-2), and quantitative electroencephalography. The primary efficacy measure was the response rate.
The response rate was 90% based on a 30% or greater decline in the ARS-I score or 85% based on CGI-I scores of 1 or 2. The mean±standard deviation ARS-I score decreased from 33.65±6.42 at baseline to 16.80±6.86 after 12 weeks of EAA/T (p<0.001, paired t-test). EAA/T also resulted in significant improvement in the social problems subscale of the K-CBCL and in the manual dexterity, bilateral coordination, and total motor composite subscales of the BOT-2. The theta/beta ratio on electroencephalography was decreased significantly at the Pz electrode after 12 weeks of EAA/T.
This is the first study demonstrating that EAA/T is effective for improving core ADHD symptoms. On the basis of these results, EAA/T could be a viable treatment strategy as a part of a multimodal therapy for children with ADHD.
No preview · Article · Jul 2015 · Journal of alternative and complementary medicine (New York, N.Y.)
[Show abstract][Hide abstract] ABSTRACT: Background:
Women are subject to a disproportionate burden from Alzheimer's disease (AD) and sex differences exist in treatment response and prognosis of the disease. Yet gender-specific risk factors have not been widely studied. We aimed to investigate gender-specific risk factors for AD in subjects with mild cognitive impairment (MCI).
Participants (n=294) with MCI were recruited from a nationwide, prospective cohort study of dementia and were followed for a median (range) of 13.8 (6.0-36.0) months. Sex-stratified associations of progression to AD with baseline characteristics were explored.
Seventy-four individuals (25.2%) developed incident dementia (67AD) during follow-up. Significant risk factors for probable AD differed by sex. In men, the significant risk factors were severe periventricular white matter hyperintensities, and poorer global cognitive function. In women, older age, clinically significant depressive symptoms at baseline, and positive APOE ε4 alleles were the significant risk factors.
Risk factors for progression from MCI to probable AD differed in men and women. These results may translate to gender-specific preventative or therapeutic strategies for patients with MCI.
[Show abstract][Hide abstract] ABSTRACT: We investigated the vitamin D status of Korean women during pregnancy and assessed the effects of vitamin D deficiency on two pregnancy outcomes; preterm births and the births of small for gestational age. We measured the serum 25-hydroxyvitamin D levels in 220 pregnant Korean women who were recruited prospectively and compared these levels with those of 500 healthy non-pregnant women. We analyzed vitamin D status according to patient demographics, season, and obstetrical characteristics; moreover, we also assessed pregnancy outcomes. The overall prevalence of vitamin D deficiency(<20 ng/mL) in pregnant women and healthy non-pregnant women was 77.3% and 79.2%; respectively; and the prevalence of severe vitamin D deficiency (<10 ng/mL) was 28.6% and 7.2%; respectively (p < 0.05). Vitamin D deficiency was more prevalent in the winter (100%) than in the summer (45.5%) in pregnant Korean women. A higher risk of vitamin D deficiency was observed in the first trimester than in the third trimester (adjusted OR 4.3; p < 0.05). No significant association was observed between vitamin D deficiency and any of the pregnancy outcomes examined. Further research focusing on the long-term consequences of vitamin D deficiency during pregnancy in Korean women is warranted.
[Show abstract][Hide abstract] ABSTRACT: In clinical studies, patients are often classified into high or low risk groups based on prognostic factors related to survival outcomes. Using maximally selected linear rank statistics, several methods have been developed to determine a cutoff value of the prognostic factor. We propose an extension of these methods for the circumstances that competing risks are encountered in conjunction with an event outcome of interest. A simulation study is carried out to demonstrate the performance of the proposed method using some commonly used measures such as bias, precision, and power. We also apply our method to two real datasets involving lung cancer and hepatocellular carcinoma, illustrating optimal determinations of cutoff values for binary decisions on prognosis.
No preview · Article · Apr 2015 · Computational Statistics
[Show abstract][Hide abstract] ABSTRACT: The risk factors for venous thromboembolism (VTE) in diffuse large B-cell lymphoma (DLBCL) are not clear although thrombosis can be associated with host status, tumor burden and inflammatory activity. We assessed the effect of those factors on VTE in a cross-sectional study of patients enrolled in a prospective cohort study.
We analyzed the occurrence of VTE in 322 patients with newly diagnosed DLBCL who received R-CHOP (rituximab cyclophosphamide, doxorubicin, vincristine, and prednisone) between 2008 and 2011. Serum levels of inflammatory cytokines were measured from serum samples archived at diagnosis.
With a median follow-up duration of 41.9 months, VTE was documented in 34 patients (10.6%). A comparison of baseline characteristics indicated the group with VTE had higher percentage of old age, stage III/IV and extranodal involvements than the group without VTE (P < 0.05). Thus, the International Prognostic Index was significantly associated with VTE, but the Khorana score was not. A univariate competing risk factor analysis for VTE revealed that increased levels of inflammatory cytokines such as interleukin (IL)-6 and IL-10 were also associated with VTE (P < 0.05) in addition to host and tumor burden. However, a multivariate analysis showed that two host factors including age ( 60 years) and poor performance were independent risk factors for VTE.
s Among potential risk factors for VTE including tumor burden and inflammatory activity, age and performance status had a strong impact on the occurrence of VTE in patients with DLBCL who received R-CHOP.
Preview · Article · Mar 2015 · Cancer Research and Treatment
[Show abstract][Hide abstract] ABSTRACT: Genetic polymorphism contributes to variation in response to drug treatment of depression. We conducted three independent 6-week treatment studies in outpatients with major depressive disorder (MDD) to develop a pharmacogenomic model predicting response and nonresponse. We screened candidate genomic markers for association with response to selective serotonin reuptake inhibitors (SSRIs). No patients had received any antidepressant drug treatment in the current episode of depression. Outcome evaluation was blinded to drug and genotype data. The prediction model derived from a development sample of 239 completer cases treated with SSRIs comprised haplotypes and polymorphisms related to serotonin synthesis, serotonin transport, glutamate receptors, and GABA synthesis. The model was evaluated prospectively for prediction of outcome in a validation sample of 176 new SSRI-treated completer cases. The model gave a prediction in 60% of these cases. Predictive values were 85% for predicted responders and 86% for predicted nonresponders, compared to prior probabilities of 66% for observed response and 34% for observed nonresponse in those cases (both P<0.001). Convergent cross-validation was obtained through failure of the model to predict outcomes in a third independent sample of 189 completer cases who received non-SSRI antidepressants. We suggest proof of principle for genetic guidance to use or avoid SSRIs in a majority of Korean depressed patients.
[Show abstract][Hide abstract] ABSTRACT: Background
The incidence, risk factors and management strategy of paradoxical reaction to midazolam during endoscopy are yet to be clarified.
This single center prospective study included 4140 adult patients (2263 males, mean age of 57.7 ± 12.6) undergoing endoscopy under sedation with midazolam and pethidine between September 2011 and December 2011. The characteristics of patients with and without paradoxical reaction were compared. For patients who experienced paradoxical reaction and received flumazenil, their endoscopic images were reviewed to assess whether European Society of Gastrointestinal Endoscopy guidelines were met as quality indicator of endoscopy.
The incidence of paradoxical reaction was 1.4%. In multivariate analyses, male gender, unsuccessful sedation in previous endoscopy, upper endoscopy, higher dose of midazolam, and lower dose of pethidine were identified as independent risk factors for paradoxical reaction. Despite paradoxical reaction, endoscopic procedures were successfully completed in 93.3% of cases when flumazenil was administered. The rates of meeting quality indicator of endoscopy were 92.3% in patients receiving flumazenil for paradoxical reaction and 97.6% in patients without paradoxical reaction.
For patients with risk factors for paradoxical reaction, active use of pethidine with a dose reduction of midazolam might be helpful to prevent the occurrence of paradoxical reaction. Administration of flumazenil might be positively considered in cases of paradoxical reaction.
No preview · Article · Aug 2014 · Digestive and Liver Disease
[Show abstract][Hide abstract] ABSTRACT: Objective
Caregivers for patients with Alzheimer's disease (AD) suffer from psychological and financial burdens. However, the results of the relationship between burden and cognitive function, performance of activities of daily living, and depressive symptoms have remained inconsistent. Therefore, the aim of this study was to examine which factors are more significant predictors of heightened burden, cognitive impairment or functional decline, besides neuropsychiatric symptoms.
A cross-sectional study was conducted in a sample comprised of 1,164 pairs of patients with AD and caregivers from the Clinical Research of Dementia of South Korea study cohorts. The cognitive function of each sub-domain, functional impairments, depressive symptoms, and caregiver burden were assessed using the dementia version of Seoul Neuropsychological Screening Battery (SNSB-D), Barthel Index for Daily Living Activities (ADL), Seoul-Instrumental Activities of Daily Living (S-IADL), the Clinical Dementia Rating Sum of Box (CDR-SB), the Global Deterioration Scale (GDS), the Korean version of the Neuropsychiatric Inventory (K-NPI), and the 15-item Geriatric Depression Scale.
We found that higher severity (higher CDR-SB and GDS scores) and more functional impairment (lower ADL and higher S-IADL scores) were significantly associated with higher caregiver burden. In addition, depressive symptoms of patients (higher Geriatric Depression Scale scores) were associated with higher caregiver burden.
Therefore, interventions to help maintain activities of daily living in patients with AD may alleviate caregiver burden and improve caregiver well-being.