1.IL28B Is Associated with Outcomes of Chronic HBV Infection.
Xiaodong SHI ; Xiumei CHI ; Yu PAN ; Yanhang GAO ; Wanyu LI ; Chen YANG ; Jin ZHONG ; Damo XU ; Manna ZHANG ; Gerald MINUK ; Jing JIANG ; Junqi NIU
Yonsei Medical Journal 2015;56(3):625-633
PURPOSE: The role of IL28B gene variants and expression in hepatitis B virus (HBV) infections are not well understood. Here, we evaluated whether IL28B gene expression and rs12979860 variations are associated with HBV outcomes. MATERIALS AND METHODS: IL28B genetic variations (rs12979860) were genotyped by pyrosequencing of DNA samples from 137 individuals with chronic HBV infection [50 inactive carriers (IC), 34 chronic hepatitis B (CHB), 27 cirrhosis, 26 hepatocellular carcinoma (HCC)], and 19 healthy controls. IL28A/B mRNA expression in peripheral blood mononuclear cells was determined by qRT-PCR, and serum IL28B protein was measured by ELISA. RESULTS: Patients with IL28B C/C genotype had greater IL28A/B mRNA expression and higher IL28B protein levels than C/T patients. Within the various disease stages, compared to IC and healthy controls, IL28B expression was reduced in the CHB, cirrhosis, and HCC cohorts (CHB vs. IC, p=0.02; cirrhosis vs. IC, p=0.01; HCC vs. IC, p=0.001; CHB vs. controls, p<0.01; cirrhosis vs. controls, p<0.01; HCC vs. controls, p<0.01). When stratified with respect to serum HBV markers in the IC and CHB cohorts, IL28B mRNA and protein levels were higher in HBeAg-positive than negative individuals (p=0.01). Logistic regression analysis revealed that factors associated with high IL28B protein levels were C/C versus C/T genotype [p=0.016, odds ratio (OR)=0.25, 95% confidence interval (CI)=0.08-0.78], high alanine aminotransferase values (p<0.001, OR=8.02, 95% CI=2.64-24.4), and the IC stage of HBV infection (p<0.001). CONCLUSION: Our data suggest that IL28B genetic variations may play an important role in long-term development of disease in chronic HBV infections.
Adult
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Aged
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Alanine Transaminase/blood
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Asian Continental Ancestry Group/*genetics
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Biological Markers/blood
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Carcinoma, Hepatocellular/genetics
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Case-Control Studies
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China
;
DNA, Viral/blood
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Enzyme-Linked Immunosorbent Assay
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Female
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Genotype
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Hepatitis B virus/genetics
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Hepatitis B, Chronic/ethnology/*genetics/immunology/*virology
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Humans
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Interleukins/blood/*genetics/metabolism
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Leukocytes, Mononuclear
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Liver Cirrhosis/blood
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Liver Neoplasms/genetics
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Male
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Middle Aged
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RNA, Messenger/*genetics
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Reverse Transcriptase Polymerase Chain Reaction
2.Metabolic syndrome criteria as predictors of subclinical atherosclerosis based on the coronary calcium score.
Mi Hae SEO ; Eun Jung RHEE ; Se Eun PARK ; Cheol Young PARK ; Ki Won OH ; Sung Woo PARK ; Won Young LEE
The Korean Journal of Internal Medicine 2015;30(1):73-81
BACKGROUND/AIMS: The aim was to determine which of three sets of metabolic syndrome (MetS) criteria (International Diabetes Federation [IDF], National Cholesterol Education Program Adult Treatment Panel III [ATP III], and European Group for the Study of Insulin Resistance [EGIR]) best predicts the coronary artery calcification (CAC) score in a cross-sectional study. This has not been evaluated in previous studies. METHODS: A total of 24,060 subjects were screened for CAC by multi-detector computed tomography. The presence of CAC was defined as a CAC score > 0. The odds ratio for the presence of CAC was analyzed for three different sets of MetS criteria and according to number of MetS components. RESULTS: CAC was observed in 12.6% (3,037) of the subjects. Patients with MetS, as defined by the IDF, ATP III, and EGIR criteria, had a CAC rate of 23.0%, 25.1%, and 29.5%, respectively (p < 0.001). Comparisons of C statistics for multivariate regression models revealed no significant difference among the three sets of criteria. After adjustment for risk factors, the ATP III criteria produced a slightly higher odds ratio for CAC compared with the other criteria, but this difference was not significant. The risk factor-adjusted odds ratio for the presence of CAC increased from 1 to 1.679 as the number of MetS components defined by ATP III increased from 0 to > or = 3 (p for trend < 0.001). CONCLUSIONS: The presence of MetS was associated with the presence of CAC. There was no significant difference among the three sets of MetS criteria in terms of the ability to predict CAC. An increase in the number of MetS components was associated with an increased odds of CAC.
Adult
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Asymptomatic Diseases
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Biological Markers/blood
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Calcium/*analysis
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Coronary Angiography/methods
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Coronary Artery Disease/blood/*epidemiology/radiography
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Coronary Vessels/*chemistry/radiography
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Cross-Sectional Studies
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Female
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Humans
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Male
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Metabolic Syndrome X/blood/diagnosis/*epidemiology
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Middle Aged
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Multidetector Computed Tomography
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Multivariate Analysis
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Odds Ratio
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Predictive Value of Tests
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Prevalence
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Republic of Korea/epidemiology
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Risk Assessment
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Risk Factors
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Vascular Calcification/blood/*epidemiology/metabolism/radiography
3.Avoiding or coping with severe hypoglycemia in patients with type 2 diabetes.
The Korean Journal of Internal Medicine 2015;30(1):6-16
Hypoglycemia is a major barrier to achieving the glycemic goal in patients with type 2 diabetes. In particular, severe hypoglycemia, which is defined as an event that requires the assistance of another person to actively administer carbohydrates, glucagon, or take other corrective actions, is a serious clinical concern in patients with diabetes. If severe hypoglycemia is not managed promptly, it can be life threatening. Hypoglycemia-associated autonomic failure (HAAF) is the main pathogenic mechanism behind severe hypoglycemia. Defective glucose counter-regulation (altered insulin secretion, glucagon secretion, and an attenuated increase in epinephrine during hypoglycemia) and a lack of awareness regarding hypoglycemia (attenuated sympathoadrenal activity) are common components of HAAF in patients with diabetes. There is considerable evidence that hypoglycemia is an independent risk factor for cardiovascular disease. In addition, hypoglycemia has a significant influence on the quality of life of patients with diabetes. To prevent hypoglycemic events, the setting of glycemic goals should be individualized, particularly in elderly individuals or patients with complicated or advanced type 2 diabetes. Patients at high-risk for the future development of severe hypoglycemia should be selected carefully, and intensive education with reinforcement should be implemented.
Autonomic Nervous System/physiopathology
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Biological Markers/blood
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Blood Glucose/*drug effects/metabolism
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Diabetes Mellitus, Type 2/blood/complications/diagnosis/*drug therapy/physiopathology
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Health Knowledge, Attitudes, Practice
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Humans
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Hypoglycemia/blood/chemically induced/epidemiology/physiopathology/*prevention & control
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Hypoglycemic Agents/*adverse effects
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Incidence
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Patient Education as Topic
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Prevalence
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Prognosis
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Risk Assessment
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Risk Factors
4.The Difference of Lymphocyte Subsets Including Regulatory T-Cells in Umbilical Cord Blood between AGA Neonates and SGA Neonates.
Sang Hee YOON ; Mina HUR ; Han Sung HWANG ; Han Sung KWON ; In Sook SOHN
Yonsei Medical Journal 2015;56(3):798-804
PURPOSE: This study aimed to compare the regulatory T cells in cord blood of appropriate for gestational age (AGA) neonates with those of small for gestational age (SGA) neonates. MATERIALS AND METHODS: Umbilical cord blood was collected upon labor in 108 healthy full-term (between 37 and 41 gestational weeks) neonates, who were born between November 2010 and April 2012. Among them, 77 samples were obtained from AGA neonates, and 31 samples were obtained from SGA neonates. Regulatory T cells and lymphocyte subsets were determined using a flow cytometer. Student's t-test for independent samples was used to compare differences between AGA and SGA neonates. RESULTS: Regulatory T cells in cord blood were increased in the SGA group compared with normal controls (p=0.041). However, cytotoxic T cells in cord blood were significantly decreased in the SGA group compared with normal controls (p=0.007). CONCLUSION: This is the first study to compare the distribution of lymphocyte subsets including regulatory T cells in cord blood between AGA neonates and SGA neonates.
Biological Markers/metabolism
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Female
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Fetal Blood/*immunology
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Gestational Age
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Humans
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Infant, Newborn/*blood
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Infant, Small for Gestational Age/*blood
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Lymphocyte Count
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T-Lymphocytes, Cytotoxic/metabolism
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T-Lymphocytes, Regulatory/*metabolism
5.Dual ectopic thyroid presenting with an anterior neck mass.
Hannah SEOK ; Su Jin OH ; Won Chul HA ; Hyun Shik SON ; Tae Seo SOHN
The Korean Journal of Internal Medicine 2015;30(1):129-130
No abstract available.
Adult
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Biological Markers/blood
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Female
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Humans
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Mouth Floor
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*Neck/radiography/radionuclide imaging/ultrasonography
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Predictive Value of Tests
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Radiopharmaceuticals/diagnostic use
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Sodium Pertechnetate Tc 99m/diagnostic use
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Thyroid Dysgenesis/blood/*diagnosis/drug therapy
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Thyroid Function Tests
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*Thyroid Gland/drug effects/metabolism/radiography/radionuclide imaging/ultrasonography
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Thyrotropin/blood
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Thyroxine/blood/therapeutic use
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Tomography, X-Ray Computed
6.An insulinoma with an aberrant feeder from the splenic artery detected by super-selective arterial calcium stimulation with venous sampling.
Joon Ho MOON ; Eun Ky KIM ; Ah Reum KHANG ; Hyo Cheol KIM ; Jin Young JANG ; Young Min CHO
The Korean Journal of Internal Medicine 2015;30(1):118-121
No abstract available.
Biopsy
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Blood Glucose/metabolism
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C-Peptide/blood
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Calcium Gluconate/administration & dosage/*diagnostic use
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Female
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Humans
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Immunohistochemistry
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Injections, Intra-Arterial
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Insulin/blood
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Insulinoma/blood/*blood supply/pathology/surgery
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Middle Aged
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Pancreatic Neoplasms/blood/*blood supply/pathology/surgery
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Pancreaticoduodenectomy
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Splenic Artery/*radiography
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*Tomography, X-Ray Computed
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Treatment Outcome
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Tumor Markers, Biological/blood
7.A mild decrease of renal function is related to increased hemoglobin level during 5-year follow-up period.
Nara SHIN ; Hyunsuk KIM ; Hyo Jin KIM ; Miyeun HAN ; Sunhwa LEE ; Hyungah JO ; Huh HYUK ; Ho Jun CHIN
The Korean Journal of Internal Medicine 2014;29(3):341-351
BACKGROUND/AIMS: We analyzed chronological changes in hemoglobin according to renal function changes over a 5-year follow-up period. METHODS: We enrolled 5,266 adults with a glomerular filtration rate (GFR) > or = 60 mL/min/1.73 m2 at an initial examination at a routine health check-up; a follow-up examination was conducted 5 years later. We categorized the subjects according to GFR ratio (groups 1, 2, and 3, defined as GFRratio > or = 1.00, 0.75 to 0.99, and < 0.75, respectively). RESULTS: The mean hemoglobin level in subjects with a GFR of 60 to 74 was higher than in those with a GFR of 75 to 89 or > or = 90 mL/min/1.73 m2 at the initial examination (all p < 0.001). Among females and males, the frequencies of increased hemoglobin were 46.8% and 40.6% in the GFRratio group 1, 52.4% and 46.1% in group 2, and 59.6% and 52.5% in group 3 over the 5-year period, respectively (all p < 0.001). With multiple logistic regression, group 3 showed 1.594-fold (95% confidence interval [CI], 1.127 to 2.225) and 1.353-fold (95% CI, 1.000 to 1.830) higher likelihoods of increased hemoglobin over the 5-year follow-up period in females and males, respectively. The estimated difference in hemoglobin level was highest in group 3 in both genders. These findings were more evident in subgroups without metabolic syndrome, diabetes mellitus, hypertension, or GFR less than 90 mL/min/1.73 m2. CONCLUSIONS: Among a population with GFR > or = 60 mL/min/1.73 m2, a mild decrease in GFR over a 5-year follow-up period was associated with an increase in hemoglobin levels.
Adult
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Aged
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Biological Markers/blood
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Chi-Square Distribution
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Disease Progression
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Female
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Follow-Up Studies
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*Glomerular Filtration Rate
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Hemoglobins/*metabolism
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Humans
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Kidney/*physiopathology
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Kidney Diseases/blood/diagnosis/*physiopathology
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Logistic Models
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Male
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Middle Aged
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Multivariate Analysis
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Republic of Korea
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Time Factors
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Up-Regulation
8.Resting energy expenditure is not associated with disease activity in women with rheumatoid arthritis: cross-sectional study.
Jung Yoon CHOE ; Sung Hoon PARK ; Hwajeong LEE ; Hyun Hee KWON ; Seong Kyu KIM
The Korean Journal of Internal Medicine 2014;29(4):516-524
BACKGROUND/AIMS: Increased resting energy expenditure (REE) in rheumatoid arthritis (RA) patients is thought to be caused by hypermetabolism associated with production of proinflammatory cytokines. Our aim in the present study was to explore the possible association between REE and disease activity in females with RA. METHODS: A total of 499 female RA patients were recruited to this cross-sectional study assessing REE scores on disease activity indices (the routine assessment of patient index data 3 [RAPID3], the disease activity score 28, and the clinical/simplified disease activity index [CDAI/SDAI]) and the levels of RA-associated autoantibodies (rheumatoid factor and anticyclic citrullinated peptide [anti-CCP] antibodies). Age-matched healthy female controls (n = 131) were also enrolled. RESULTS: REE did not differ between RA patients (all patients, and those in remission or not) and controls, or between RA patients in remission or not (p > 0.05 for all comparisons). Increased REE in total RA patients was associated with younger age and a higher body mass index (BMI) (p < 0.001 and p < 0.001, respectively), but not with disease activity index scores on any of RAPID3, CDAI, or SDAI. BMI was the only clinical parameter exhibiting a significant relationship with REE quartiles (Q1 to Q4; p < 0.001); none of disease duration, functional status, or anti-CCP antibody titer in RA patients was significantly related to REE, based on analysis of covariance. CONCLUSIONS: We found no association between REE and disease activity in RA patients, implying that energy metabolism in RA patients might be independent of RA-associated systemic inflammation.
Adult
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Age Factors
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Aged
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Arthritis, Rheumatoid/blood/diagnosis/*metabolism/physiopathology
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Biological Markers/blood
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Body Mass Index
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Case-Control Studies
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Cross-Sectional Studies
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*Energy Metabolism
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Female
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Humans
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Inflammation Mediators/blood
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Middle Aged
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Peptides, Cyclic/immunology
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Predictive Value of Tests
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*Rest
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Rheumatoid Factor/blood
;
Severity of Illness Index
9.Effect of anemia correction on left ventricular structure and filling pressure in anemic patients without overt heart disease.
In Jeong CHO ; Yeung Chul MUN ; Ki Hwan KWON ; Gil Ja SHIN
The Korean Journal of Internal Medicine 2014;29(4):445-453
BACKGROUND/AIMS: There are few data on the effects of low hemoglobin levels on the left ventricle (LV) in patients without heart disease. The objective of this study was to document changes in the echocardiographic variables of LV structure and function after the correction of anemia without significant cardiovascular disease. METHODS: In total, 34 iron-deficiency anemia patients (35 +/- 11 years old, 32 females) without traditional cardiovascular risk factors or cardiovascular disease and 34 age- and gender-matched controls were studied. Assessments included history, physical examination, and echocardiography. Of the 34 patients with anemia enrolled, 20 were followed and underwent echocardiography after correction of the anemia. RESULTS: There were significant differences between the anemia and control groups in LV diameter, left ventricular mass index (LVMI), left atrial volume index (LAVI), peak mitral early diastolic (E) velocity, peak mitral late diastolic (A) velocity, E/A ratio, the ratio of mitral to mitral annular early diastolic velocity (E/E'), stroke volume, and cardiac index. Twenty patients underwent follow-up echocardiography after treatment of anemia. The follow-up results showed significant decreases in the LV end-diastolic and end-systolic diameters and LVMI, compared with baseline levels. LAVI, E velocity, and E/E' also decreased, suggesting a decrease in LV filling pressure. CONCLUSIONS: Low hemoglobin level was associated with larger cardiac chambers, increased LV, mass and higher LV filling pressure even in the subjects without cardiovascular risk factors or overt cardiovascular disease. Appropriate correction of anemia decreased LV mass, LA volume, and E/E'.
Adult
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Anemia, Iron-Deficiency/blood/diagnosis/*drug therapy/physiopathology
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Biological Markers/metabolism
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Case-Control Studies
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Echocardiography, Doppler
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Female
;
Heart Ventricles/*physiopathology/ultrasonography
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Hematinics/*therapeutic use
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Hemoglobins/metabolism
;
Humans
;
Male
;
Middle Aged
;
Prospective Studies
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Recovery of Function
;
Time Factors
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Treatment Outcome
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*Ventricular Function, Left
;
*Ventricular Pressure
;
*Ventricular Remodeling
;
Young Adult
10.Vitamin D and chronic kidney disease.
The Korean Journal of Internal Medicine 2014;29(4):416-427
Chronic kidney disease (CKD) has been recognized as a significant global health problem because of the increased risk of total and cardiovascular morbidity and mortality. Vitamin D deficiency or insufficiency is common in patients with CKD, and serum levels of vitamin D appear to have an inverse correlation with kidney function. Growing evidence has indicated that vitamin D deficiency may contribute to deteriorating renal function, as well as increased morbidity and mortality in patients with CKD. Recent studies have suggested that treatment with active vitamin D or its analogues can ameliorate renal injury by reducing fibrosis, apoptosis, and inflammation in animal models; this treatment also decreases proteinuria and mortality in patients with CKD. These renoprotective effects of vitamin D treatment are far beyond its classical role in the maintenance of bone and mineral metabolism, in addition to its pleiotropic effects on extra-mineral metabolism. In this review, we discuss the altered metabolism of vitamin D in kidney disease, and the potential renoprotective mechanisms of vitamin D in experimental and clinical studies. In addition, issues regarding the effects of vitamin D treatment on clinical outcomes are discussed.
Animals
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Biological Markers/blood
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Dietary Supplements
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Humans
;
Kidney/drug effects/*metabolism
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Renal Insufficiency, Chronic/*blood/diagnosis/drug therapy/epidemiology
;
Risk Factors
;
Treatment Outcome
;
Vitamin D/*blood/therapeutic use
;
Vitamin D Deficiency/*blood/diagnosis/drug therapy/epidemiology

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