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1.  Cost-of-Illness Trend of Thyroid Gland Disease in Korea 
Endocrinology and Metabolism  2014;29(3):248-250.
PMCID: PMC4192809  PMID: 25309782
2.  Unfounded Reports on Thyroid Cancer 
Journal of Korean Medical Science  2014;29(8):1033-1034.
PMCID: PMC4129191  PMID: 25120309
3.  Low Iodine Diet for Preparation for Radioactive Iodine Therapy in Differentiated Thyroid Carcinoma in Korea 
Endocrinology and Metabolism  2013;28(3):157-163.
Preparation for radioactive iodine (RAI) therapy includes an increased serum thyroid stimulating hormone level and a low iodine diet (LID). Because of extremely high iodine intake, some physicians have advocated a more stringent LID for greater than 2 weeks in Korean patients with thyroid cancer prior to RAI therapy; however, it is very difficult to maintain a stringent LID for a longer period of time. According to recent reports in Korea, a nonstringent, simple LID for only 1 week might be enough prior to RAI therapy, if the patients can be educated intensively by specially trained staff. The measurement of simple urinary iodine concentration (UIC; µg/L) may underestimate daily iodine excretion in patients with a urinary volume of more than 1 L/day and can also be affected by dilution status. Simple UIC had a weaker correlation than the iodine/creatinine (I/Cr) ratio. Therefore, the urinary I/Cr ratio can replace 24-hour urine iodine excretion instead of simple UIC, although it may overestimate iodine intake in patients with malnutrition or poor muscle mass. The measurement of serum iodine level might be useful as an adjunct parameter for assessing LID preparation, but its sensitivity and specificity were relatively low compared to the urinary I/Cr ratio.
PMCID: PMC3811704  PMID: 24396673
Radioactive iodine; Iodine; Low iodine diet; Urinary iodine concentration; Urinary iodine excretion
4.  Autosomal Dominant Hypocalcemia Caused by an Activating Mutation of the Calcium-Sensing Receptor Gene: The First Case Report in Korea 
Journal of Korean Medical Science  2010;25(2):317-320.
Hypoparathyroidism is an abnormality of calcium metabolism characterized by low serum levels of parathyroid hormone in spite of hypocalcemia. The causes of hypoparathyroidism are numerous. Activating mutations in the calcium-sensing receptor (CaSR) gene are well-known causes of familial isolated hypoparathyroidism, also known as autosomal dominant hypocalcemia (ADH). Here we describe members of a Korean family with a heterozygous Pro221Leu mutation causing ADH. This case is the first report in Korea.
PMCID: PMC2811305  PMID: 20119591
Hypoparathyroidism; Hypocalcemia; Receptors, Calcium-Sensing
5.  Overexpression of USF Increases TGF-β1 Protein Levels, But G1 Phase Arrest was not Induced in FRTL-5 Cells 
Journal of Korean Medical Science  2008;23(5):870-876.
Transforming growth factor-β1 (TGF-β1) is a potent inhibitor of cellular growth and proliferation by G1 phase arrest or apoptosis. We investigated the association of TGF-β1 with the anti-proliferative effect of upstream stimulatory factor (USF) in Fischer rat thyroid cell line (FRTL-5) cells. [Methyl-3H] thymidine uptake was measured after treatment of FRTL-5 cells with TGF-β1 to identify its anti-proliferative effect. USF-1 and USF-2 proteins were in vitro translated, and an electrophoretic mobility shift assay was performed to identify the interaction between USF and the TGF-β1 promoter. FRTL-5 cells were transfected with USF cDNA, and then the expression of TGF-β1 was examined with Northern and Western blotting. The cell cycle-regulating proteins associated with TGF-β1 were also measured. TGF-β1 significantly inhibited [methyl-3H] thymidine uptake in FRTL-5 cells. Two specific binding sites for USF were found in the TGF-β1 promoter: -1,846~-1,841 (CACATG) and -621~-616 (CATGTG). Overexpression of USF increased both the mRNA levels and protein levels of TGF-β1. However, the expression of cyclin D1, CDK4, cyclin E, and CDK2, and the phosphorylation of retinoblastoma protein remained unchanged. Overexpression of USF in FRTL-5 cells increased the expression of TGF-β10 through specific binding to TGF-β1 promoter. However, the USF-induced expression of TGF-β1 did not cause G1 arrest.
PMCID: PMC2580023  PMID: 18955796
Upstream Stimulatory Factor; Transforming Growth Factor beta1; FRTL-5 Cells
6.  A Patient with Primary Squamous Cell Carcinoma of the Thyroid Intermingled with Follicular Thyroid Carcinoma that Remains Alive more than 8 Years after Diagnosis 
Primary squamous cell carcinoma of the thyroid is an extremely rare tumor with a highly aggressive clinical course. We report here on a patient with primary squamous cell carcinoma of the thyroid who remains alive more than 8 years after diagnosis. A 56-year-old man presented with a hoarse voice and a rapidly progressing mass on the right side of the thyroid gland. The patient underwent a total thyroidectomy without neck lymph node dissection. Histopathologic findings revealed primary squamous cell carcinoma combined with follicular carcinoma of the thyroid. The tumors metastasized to the cervical lymph nodes, thoracic spine and lung. He underwent 5000 rads of adjuvant radiotherapy to the neck. TSH suppressive therapy with L-thyroxine was administered alone rather than radioactive iodine therapy or chemotherapy. The patient's clinical course has been remarkable over the first 7 years; he has remained stable except for a transient paraplegia due to nerve compression. The patient underwent colectomy for the diagnosis of a colon cancer. Recent evaluation has revealed a new lesion in the lung; this was diagnosed as metastatic follicular carcinoma originating from the thyroid. High dose radioactive iodine therapy was administered, and he remains alive in stable condition.
PMCID: PMC3891069  PMID: 16646570
Squamous cell carcinoma; Adenocarcinoma; Follicular; Thyroid neoplasm
7.  Effectiveness of 3-Day Continuous Glucose Monitoring for Improving Glucose Control in Type 2 Diabetic Patients in Clinical Practice 
Diabetes & Metabolism Journal  2014;38(6):449-455.
The aim of this study was to investigate whether adjusting diabetic treatment regimens according to the information obtained from a continuous glucose monitoring system (CGMS) might lead to improved glycemic control in patients with type 2 diabetes.
We reviewed the medical charts of 172 patients who used the CGMS for 1 year starting in December 2008 and the records of 1,500 patients who visited their regular outpatient clinics during December 2008. Of these patients, a total of 65 CGMS patients and 301 regular outpatients (control group) were enrolled in the study after propensity score matching. There were no differences in baseline glycated hemoglobin (HbA1c), age, and duration of diabetes between the CGMS and the control groups after propensity score matching. The changes in the HbA1c levels from baseline to 6 months were calculated.
The CGMS group showed a significant improvement in the HbA1c level compared to the control group at 3 months (7.9%±1.6% vs. 7.4%±1.2%, P=0.001) and at 6 months (7.4%±1.2% vs. 7.9%±1.6%, P=0.010). There were significant differences in the treatment modality changes between the CGMS group and the control group.
Using a 3-day CGMS was advantageous for improving glucose control in patients with type 2 diabetes and may help these patients to optimize glycemic control in clinical practice.
PMCID: PMC4273031  PMID: 25541608
Continuous glucose monitoring; Diabetes mellitus, type 2; Hemoglobin A, glycosylated
8.  The Validity of Ultrasonography-Guided Fine Needle Aspiration Biopsy in Thyroid Nodules 4 cm or Larger Depends on Ultrasonography Characteristics 
Endocrinology and Metabolism  2014;29(4):545-552.
The objective of this study was to evaluate the validity of fine needle aspiration biopsy (FNAB) according to ultrasonography (US) characteristics in thyroid nodules 4 cm and larger.
We retrospectively reviewed the cases of 263 patients who underwent thyroid surgery for thyroid nodules larger than 4 cm between January 2001 and December 2010.
The sensitivity of US-FNAB was significantly higher in nodules with calcifications (micro- or macro-) than those without (97.9% vs. 87.% P<0.05). The accuracy of US-FNAB was higher in large thyroid nodules with US features suspicious of malignancy, such as a solid component, ill-defined margin, hypoechogenicity or marked hypoechogenicity, or any calcifications (micro- or macro-) compared to thyroid nodules with none of these features. Furthermore, the accuracy improved as the number of these features increased. The overall false negative rate (FNR) was 11.9%. The FNR of thyroid nodules that appeared benign on US, such as mixed nodules (7.7%) or nodules without calcification (9.8%), trended toward being lower than that of solid nodules (17.9%) or nodules with any microcalcification or macrocalcification (33.3%). In nodules without suspicious features of malignancy, the FNR of US-FNAB was 0% (0/15).
We suggest individualized strategies for large thyroid nodules according to US features. Patients with benign FNAB can be followed in the absence of any malignant features in US. However, if patients exhibit any suspicious features, potential false negative results of FNAB should be kept in mind and surgery may be considered.
PMCID: PMC4285035  PMID: 25325261
Biopsy, fine-needle; Validity; Reliability; Ultrasonography; Thyroid nodule
9.  Using Growth Hormone Levels to Detect Macroadenoma in Patients with Acromegaly 
Endocrinology and Metabolism  2014;29(4):450-456.
The aim of this study was to assess the clinical differences between acromegalic patients with microadenoma and patients with macroadenoma, and to evaluate the predictive value of growth hormone (GH) levels for early detection of macroadenoma.
We performed a retrospective analysis of 215 patients diagnosed with a GH-secreting pituitary adenoma. The patients were divided into two groups: the microadenoma group and the macroadenoma group, and the clinical parameters were compared between these two groups. The most sensitive and specific GH values for predicting macroadenoma were selected using receiver operating characteristic (ROC) curves.
Compared with the microadenoma group, the macroadenoma group had a significantly younger age, higher body mass index, higher prevalence of hyperprolactinemia and hypogonadism, and a lower proportion of positive suppression to octreotide. However, there were no significant differences in the gender or in the prevalence of diabetes between the two groups. The tumor diameter was positively correlated with all GH values during the oral glucose tolerance test (OGTT). All GH values were significantly higher in the macroadenoma group than the microadenoma group. Cut-off values for GH levels at 0, 30, 60, 90, and 120 minutes for optimal discrimination between macroadenoma and microadenoma were 5.6, 5.7, 6.3, 6.0, and 5.8 ng/mL, respectively. ROC curve analysis revealed that the GH value at 30 minutes had the highest area under the curve.
The GH level of 5.7 ng/mL or higher at 30 minutes during OGTT could provide sufficient information to detect macroadenoma at the time of diagnosis.
PMCID: PMC4285038  PMID: 25325263
Acromegaly; Microadenoma; Macroadenoma; Growth hormone; Glucose tolerance test
10.  Randomized Controlled Trials In Endourology: A Quality Assessment 
Journal of Endourology  2013;27(8):1055-1060.
To analyze the quality of studies reporting randomized clinical trials (RCTs) in the field of endourology.
Materials and Methods
RCTs published in the Journal of Endourology from 1993 until 2011 were identified. The Jadad scale, van Tulder scale, and Cochrane Collaboration Risk of Bias Tool (CCRBT) were used to assess the quality of the studies. The review period was divided into early (1993–1999), mid (2000–2005), and late (2006–2011) terms. Studies were categorized by country of origin, subject matter, single- vs multicenter setting, Institutional Review Board (IRB) approval and funding support, and blinding vs nonblinding.
In total, 3339 articles had been published during the defined review period, of which 165 articles were reporting a RCT. There was a significant increase in the number of RCTs published over time, with 18 (2.81%), 43 (4.88%), and 104 (5.72%) studies identified in the early, mid, and late term, respectively (P=0.009). Nevertheless, there was no difference in terms of quality of reporting, as assessed with the Jadad scale, van Tulder scale, or CCRBT, between the three study terms. On the other hand, significant differences were found in both the number of high qualitative RCTs that used blinding methodology and those that had IRB review, when comparing the early, mid, and late terms.
There has been a growing number of Journal of Endourology publications reporting on RTC over the last two decades. The quality of reporting for these studies remains suboptimal, however. Researchers should focus on a more appropriate description of key features of any given RCT, such as randomization and allocation methods, as well as disclosure of IRB review and financial support.
PMCID: PMC3741436  PMID: 23767666
11.  High Dietary Sodium Intake Assessed by 24-hour Urine Specimen Increase Urinary Calcium Excretion and Bone Resorption Marker 
Journal of Bone Metabolism  2014;21(3):189-194.
The average dietary sodium intake of Koreans is 2.6 times higher than the World Health Organization's recommended amount. The effect of a diet high in sodium on the skeletal system, especially osteoporosis, has not previously been examined in Korean postmenopausal women with low bone mass. We assessed the daily sodium intake, and determined the impact of sodium intake on urinary calcium excretion and bone resorption marker.
A retrospective review of medical records was performed for 86 postmenopausal subjects who were initially diagnosed with osteopenia or osteoporosis at the health promotion center. They were subsequently referred to the Division of Endocrinology and Metabolism between 2010 and 2013. All subjects completed a modified food frequency questionnaire. Twenty-four hour urine collection for sodium, calcium and creatinine excretion, and serum C-terminal telopeptides of type I collagen (CTX-I) were also obtained.
The average amount of daily sodium and calcium intake were 3,466 mg and 813 mg, respectively. Average dietary sodium intake and 24-hour urinary sodium excretion showed significant positive linear correlation (r=0.29, P=0.006). There was also a significant positive linear correlation between 24-hour urine sodium and calcium excretion (r=0.42, P<0.001); CTX-I and 24-hour urinary calcium excretion (r=0.29, P=0.007).
Excessive sodium intake assessed by 24-hour urine specimen is associated with high calcium excretion in urine. High calcium excretion is also related to increasing bone resorption marker.
PMCID: PMC4170081  PMID: 25247156
Bone resorption marker; Dietary sodium intake; Urinary calcium excretion; Urinary sodium excretion
12.  Association Between Excessive Urinary Iodine Excretion and Failure of Radioactive Iodine Thyroid Ablation in Patients with Papillary Thyroid Cancer 
Thyroid  2013;23(6):741-747.
A low-iodine diet (LID) is usually recommended for a week or two before radioactive iodine (RAI) ablation therapy in papillary thyroid cancer (PTC) patients after total thyroidectomy. However, it is still controversial whether an LID affects ablation outcomes. We therefore evaluated the association between urinary iodine excretion and the rate of successful ablation and investigated the determinants of successful RAI ablation outcomes.
We retrospectively reviewed the records of 295 consecutive patients with PTC who received 1110 MBq RAI remnant ablation therapy with thyroid hormone withdrawal after total thyroidectomy. Successful ablation was defined as either no visible or faint uptake on a follow-up scan (definition 1), or no visible or faint uptake on a follow-up scan and a stimulated thyroglobulin level <2 ng/mL (definition 2).
The proportion of patients with appropriate LID status (defined as a urinary iodine concentration [UIC] <66.2 μg iodine/g creatinine [μg/gCr]) was significantly higher in the successfully ablated group (81% vs. 67%, p=0.03). Based on definition 1, 80.3% (237/295) of patients were successfully ablated. The ablation rate was significantly lower in patients who had a UIC >250 μg/gCr at the time of RAI ablation (p<0.05). In multivariate analysis, a UIC >250 μg/gCr was the only significant variable associated with ablation failure (p=0.002, odds ratio [OR] 4.74 [95% confidence interval (CI) 1.78–12.63]). Based on definition 2, 74.9% (221/295) of patients were successfully ablated. A UIC >250 μg/gCr at RAI administration showed a significant association with ablation failure (p<0.05). The OR of a UIC >250 μg/gCr for ablation failure was 3.88 [CI 1.42–10.57] (p=0.008).
Excessive iodine intake (UIC >250 μg/gCr) was associated with poor RAI ablation outcomes. Because this amount of iodine is very high, we propose that the level of strictness of the LID protocol should be modified according to the region that the patient is from and the food that the patient is accustomed to eating. Even in those areas where iodine intake is high, overly strict compliance with an LID protocol is not necessary and simple recommendations to avoid iodine-rich foods would be appropriate.
PMCID: PMC3675834  PMID: 23205883
13.  Follicular and Hurthle cell carcinoma of the thyroid in iodine-sufficient area: retrospective analysis of Korean multicenter data 
Follicular thyroid carcinoma (FTC) and Hurthle cell carcinoma (HCC) of the thyroid are relatively uncommon thyroid malignancies in iodine-sufficient areas. In this study we evaluated the clinical behavior, prognostic factors and treatment outcomes of FTC and HCC in Korea.
This multicenter study included 483 patients with FTC and 80 patients with HCC who underwent an initial surgery between 1995 and 2006 in one of the four tertiary referral hospitals in Korea. We evaluated clinicopathological factors associated with distant metastases and recurrence during a median of 6 years of follow-up.
HCC patients were significantly older (49 years vs. 43 years; p < 0.001) and had more lymphovascular invasions (22% vs. 14%; p = 0.03) compared with FTC patients. Distant metastases were confirmed in 40 patients (8%) in the FTC group and in two patients (3%) in the HCC group (p = 0.07). Distant metastases were significantly associated with older age, widely invasive cancer and extrathyroidal invasion. Only 14 patients (3%) had recurrent disease and there was no significant difference between FTC and HCC groups (p = 0.38). Recurrence was associated with larger tumor size and cervical lymph node metastasis.
HCC patients were older and had more lymphovascular invasions than FTC patients. However, FTC and HCC patients had similar initial clinicopathological features. Older age, wide invasiveness and extrathyroidal invasion were independent risk factors for predicting distant metastases in FTC and HCC patients.
PMCID: PMC4028522  PMID: 24851067
Follicular adenocarcinoma; Hurthle cell thyroid cancer; Distant metastases; Prognosis; Iodine
14.  Predictive factors of durability to sitagliptin: Slower reduction of glycated hemoglobin, older age and higher baseline glycated hemoglobin 
The goal of the present study was to evaluate predictive factors for good efficacy and durability to sitagliptin with ongoing metformin or metformin plus glimepiride therapy in a real practice situation. The present observational study was carried out over a 60‐week period and involved Korean patients with type 2 diabetes mellitus.
Materials and Methods
A total of 100 mg of sitagliptin were added once daily to the two most popular therapy regimens (group 1: metformin, group 2: metformin plus glimepiride). Before adding sitagliptin, mean initial glycated hemoglobin (HbA1c) levels were 7.8% (62 mmol/mol) and mean diabetes duration was 8.3 years.
After 60 weeks, the mean change in HbA1c from baseline was −0.9% (−10 mmol/mol) in group 1 and −1.0% (−11 mmol/mol) in group 2. Decreased HbA1c levels were significantly associated with higher initial HbA1c and lower log‐transformed C‐peptide levels in a multivariate regression analysis. Logistic regression analysis showed that a sustained reduction in HbA1c levels after 12 weeks was significantly associated with older age (≥60 years), higher baseline HbA1c (group 1 ≥ 7.0% [53 mmol/mol], group 2 ≥ 7.5% [58 mmol/mol]) and slower reduction of HbA1c (ΔHbA1c <1.0% [11 mmol/mol]) in group 1 and group 2. In group 2, a higher ratio of reduction of postprandial glucose/reduction of fasting plasma glucose (ΔPPG/ΔFPG) during 12 weeks was also associated with a sustained reduction in HbA1c levels after 12 weeks.
The effects of sitagliptin lasted more than 12 weeks in older patients with a higher baseline HbA1c, and slower reduction of HbA1c during 12 weeks.
PMCID: PMC4025229  PMID: 24843737
Sitagliptin; Durability; Predictive factors
15.  A Case of Partial Congenital Pericardial Defect Presenting as Acute Coronary Syndrome 
Korean Circulation Journal  2013;43(12):845-848.
Congenital pericardial defects are rare and asymptomatic for both partial and complete defects. However, some patients can experience syncope, arrhythmia, and chest pain. When a patient experiences a symptom, it may be caused by herniation and dynamic compression or torsion of a heart structure including the coronary arteries. Diagnosis of a congenital pericardial defect may be difficult, especially in old patients with concomitant coronary artery disease. The clinical importance of congenital pericardial defect has not been stressed and congenital pericardial defects are regarded as benign, but in this case, pericardial defect was responsible for myocardial ischemia. The authors report a case of partial congenital pericardial defect causing herniation and dynamic compression of the coronary arteries, presenting as an acute coronary syndrome in an old man, with an emphasis on the unique features of the coronary angiogram that support the diagnosis of partial pericardial defects.
PMCID: PMC3875704  PMID: 24385999
Heart defects, congenital; Pericardium; Coronary artery disease
16.  Expression of Heat Shock Protein 27 in Prostate Cancer Cell Lines According to the Extent of Malignancy and Doxazosin Treatment 
The World Journal of Men's Health  2013;31(3):247-253.
Heat shock protein 27 (HSP27) is known as the material that plays a role in apoptosis control in tumor and cell protection including the immune response, drug tolerance, and so on. In this study, HSP27 expression according to the prostate cancer malignancy level was evaluated, and HSP27 expression was also analyzed after inducing apoptosis by doxazosin treatment of the prostate cancer cell lines.
Materials and Methods
Reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence staining of the HSP27 was implemented by the culture of RWPE-1, LNCaP, androgen-independent human prostate cancer cells (PC-3), and TSU-Pr1 cell lines. Analysis was separately conducted in the control group, control vector group treated by dimethyl sulfoxide, and groups treated with 10 µM or 25 µM doxazosin. The expression of HSP27 in RT-PCR and immunofluorescence staining was observed and evaluated after conversion to numerical values.
In the RT-PCR results, depending on the cell type, LNCaP, TSU-Pr1 showed the highest HSP27 expression followed by PC-3, LNCaP and RWPE-1 in sequence. After doxazosin treatment, the expression detected by RT-PCR was stronger at a 25-µM doxazosin concentration compared to that at a 10-µM concentration, and the result was similar by immunofluorescence staining.
HSP27 expression increased depending on the prostate cancer cell line. This meant that HSP27 expression was related to the prostate cancer malignancy level. Additionally, the higher the treatment concentration in PC-3 was, the higher the HSP27 expression was. This result showed that doxazosin induced apoptosis of prostate cancer.
PMCID: PMC3888895  PMID: 24459659
Fluorescent antibody technique; Heat-shock proteins; Polymerase chain reaction; Reverse transcription
17.  A Quality Analysis of Randomized Controlled Trials about Erectile Dysfunction 
The World Journal of Men's Health  2013;31(2):157-162.
A low quality clinical trial could produce errors, and these errors could, in turn, distort the results of the clinical trial. To avoid applying distorted results of trials clinically, a quality analysis of clinical trials is needed.
Materials and Methods
We selected randomized controlled trials (RCTs) about erectile dysfunction (ED) conducted in Korea using Medline and KoreaMed. Quality assessment of selected RCTs was performed using three assessment tools (Jadad scales, van Tulder scale, Cochrane Collaboration Risk of Bias Tool [CCRBT]).
The first RCT about ED conducted in Korea was published in 2002. Since 2002, a total of 20 RCTs have been published in medical journals. Among the 20 articles, only 1 article was found to have a low risk of bias according to the CCRBT. On the Jadad scale, there were 17 high quality articles, while 19 articles were assessed as high quality by the VTS. Only 2 RCTs described the randomization method adequately. Only 1 RCT presented allocation concealment.
A low quality clinical trial could produce errors, and these errors could, in turn, distort the results of the clinical trial. To avoid applying distorted results of trials clinically, a quality analysis of clinical trials is needed. The quality of RCTs was found to be high because almost all of the selected RCTs were double blinded studies. However, the quality of RCTs was inadequate with regard to the lack of randomization and absence of allocation concealment. Therefore, performing adequate randomization and adding a description of the appropriate concealment of allocation may improve the quality of RCTs.
PMCID: PMC3770851  PMID: 24044111
Randomized controlled trial; Journal article; Erectile dysfunction
18.  Assessing the Quality of Randomized Controlled Urological Trials Conducted by Korean Medical Institutions 
Korean Journal of Urology  2013;54(5):289-296.
To assess the quality of randomized controlled urological trials conducted by Korean medical institutions.
Materials and Methods
Quality assessment was conducted by using the Jadad scale; in addition, the van Tulder scale and the Cochrane Collaboration risk of bias tool were used as individual indices. All assessments were performed by two reviewers. If the outcomes differed, the two reviewers and a third reviewer adjusted the discrepancy in the results through discussion. Starting from 1986, a quality analysis of randomized controlled trials (RCTs) was conducted in 1-year and 5-year units. The quality assessment was conducted by subject, type of intervention, presence of double blinding, presence of funding, and review by an Institutional Review Board (IRB).
Whereas the number of RCTs published has gradually increased, there was no significant difference in the quality of the RCTs according to publication year. Drug studies, double-blind studies, studies with funding, and studies reviewed by IRBs had higher quality scores and a higher percentage of high-quality RCTs than did other studies. Thirty-six RCTs were published in journals included in the Science Citation Index and 20 RCTs were published in journals included in the Science Citation Index Expanded. The largest number of RCTs (32.32%) were published by the Korean Journal of Urology.
A quantitative increase was observed in RCTs over time, but no qualitative improvement in the RCTs was observed. It seems necessary to put effort into the quality improvement of RCTs at the design stage.
PMCID: PMC3659221  PMID: 23700493
Journal article; Randomized controlled trial
19.  Right Coronary Artery to Left Ventricular Fistula Associated with Infective Endocarditis of the Mitral Valve 
Korean Circulation Journal  2013;43(4):281-283.
A 27-year-old man with bacterial endocarditis of the mitral valve and embolic episodes was bound to have a large right coronary artery fistula communicating with the left ventricle, immediately inferior to the posterior mitral annulus. The perforation of the posterior leaflet and coronary arteriovenous fistula was identified using two-dimensional Doppler echocardiography. The diagnosis was confirmed by coronary angiography, and the patient underwent a successful operation.
PMCID: PMC3654119  PMID: 23682291
Endocarditis, bacterial; Fistula; Coronary vessel anomalies
20.  Brain and Skin Metastasis From Urothelial Carcinoma of the Bladder 
Korean Journal of Urology  2013;54(1):66-68.
Brain and skin metastasis from urothelial carcinoma of the bladder is rare. There have been few case reports of the clinical course of patients with metastatic urothelial carcinoma of the brain and skin. In the present case, a 60-year-old man had undergone radical cystectomy with an ileal conduit owing to urothelial carcinoma (T1N0M0). The patient developed dizziness 9 years later and a solitary brain tumor was discovered in his left cerebellar hemisphere. The tumor was totally resected and the mass was verified to be metastatic urothelial carcinoma. One year after the metastasectomy of the brain lesion, multiple erythematous nodular lesions developed on his abdominal skin. The skin lesions were excised and verified to be metastatic urothelial carcinoma. This report describes this case of urothelial carcinoma of the bladder that metastasized to the brain and abdominal skin.
PMCID: PMC3556557  PMID: 23362451
Neoplasm metastasis; Skin; Urinary bladder neoplasms
21.  Differential Findings of Tc-99m Sestamibi Dual-Phase Parathyroid Scintigraphy Between Benign and Malignant Parathyroid Lesions in Patients with Primary Hyperparathyroidism 
This study aimed to investigate the differential findings in clinical and biochemical features, and Tc-99m sestamibi (MIBI) dual-phase parathyroid scintigraphy for malignant and benign parathyroid lesions in patients with primary hyperparathyroidism.
Subjects were 102 parathyroid lesions from 91 patients with primary hyperparathyroidism. Scintigraphic findings included radioactivity grade, uptake pattern, uptake contour, lesion size on early and delayed images, and degree of washout. Clinical and biochemical features were also evaluated. Histopathology confirmed the final diagnosis for all the patients.
Final diagnoses were 94 benign parathyroid lesions and 8 parathyroid carcinomas. The patients with parathyroid carcinoma were significantly older (p = 0.002) and had significantly higher serum parathyroid hormone concentrations than those with benign parathyroid lesions (p < 0.001). All malignant parathyroid lesions showed intense radioactivity similar to or greater than the submandibular gland activity on delayed images (p = 0.007), and little radioactivity difference between early and delayed images (p = 0.012). The cancer incidence for parathyroid lesions with both intense radioactivity and no washout was 17.0% (8/47). When parathyroid lesions with all of the above-mentioned findings were regarded as malignant, the cancer incidence significantly increased from 17.0% to 33.3% (8/24, p < 0.001).
For Tc-99m MIBI dual-phase parathyroid scintigraphy, uptake grade on delayed images and washout were significantly useful diagnostic criteria for differentiating benign from malignant parathyroid lesions, along with age and parathyroid hormone serum concentration.
PMCID: PMC4043053  PMID: 24900018
Primary hyperparathyroidism; Parathyroid carcinoma; Parathyroid adenoma; Parathyroid hyperplasia; Tc-99m Sestamibi; Parathyroid scintigraphy
22.  Autophagy induction by tetrahydrobiopterin deficiency 
Autophagy  2011;7(11):1323-1334.
Tetrahydrobiopterin (BH4) deficiency is a genetic disorder associated with a variety of metabolic syndromes such as phenylketonuria (PKU). In this article, the signaling pathway by which BH4 deficiency inactivates mTORC1 leading to the activation of the autophagic pathway was studied utilizing BH4-deficient Spr-/- mice generated by the knockout of the gene encoding sepiapterin reductase (SR) catalyzing BH4 synthesis. We found that mTORC1 signaling was inactivated and autophagic pathway was activated in tissues from Spr-/- mice. This study demonstrates that tyrosine deficiency causes mTORC1 inactivation and subsequent activation of autophagic pathway in Spr-/- mice. Therapeutic tyrosine diet completely rescued dwarfism and mTORC1 inhibition but inactivated autophagic pathway in Spr-/- mice. Tyrosine-dependent inactivation of mTORC1 was further supported by mTORC1 inactivation in Pahenu2 mouse model lacking phenylalanine hydroxylase (Pah). NIH3T3 cells grown under the condition of tyrosine restriction exhibited autophagy induction. However, mTORC1 activation by RhebQ64L, a positive regulator of mTORC1, inactivated autophagic pathway in NIH3T3 cells under tyrosine-deficient conditions. In addition, this study first documents mTORC1 inactivation and autophagy induction in PKU patients with BH4 deficiency.
PMCID: PMC3242797  PMID: 21795851
tetrahydrobiopterin; autophagy; mTORC1; tyrosine; phenylalanine; phenylketonuria; Akt; AMPK
23.  A Case of Congenital Adrenal Hyperplasia Mimicking Cushing's Syndrome 
Journal of Korean Medical Science  2012;27(11):1439-1443.
Congenital adrenal hyperplasia (CAH) is characterized by decreased adrenal hormone production due to enzymatic defects and subsequent rise of adrenocorticotrophic hormone that stimulates the adrenal cortex to become hyperplastic, and sometimes tumorous. As the pathophysiology is basically a defect in the biosynthesis of cortisol, one may not consider CAH in patients with hypercortisolism. We report a case of a 41-yr-old man with a 4 cm-sized left adrenal tumorous lesion mimicking Cushing's syndrome who was diagnosed with CAH. He had central obesity and acanthosis nigricans involving the axillae together with elevated 24-hr urine cortisol level, supporting the diagnosis of Cushing's syndrome. However, the 24-hr urine cortisol was suppressed by 95% with the low dose dexamethasone suppression test. CAH was suspected based on the history of precocious puberty, short stature and a profound suppression of cortisol production by dexamethasone. CAH was confirmed by a remarkably increased level of serum 17-hydroxyprogesterone level. Gene mutation analysis revealed a compound heterozygote mutation of CYP21A2 (I173N and R357W).
PMCID: PMC3492685  PMID: 23166432
Congenital Adrenal Hyperplasia; 21-Hydroxylase Deficiency; Hypercortisolism
24.  RhoB deficiency in thymic medullary epithelium leads to early thymic atrophy 
International Immunology  2011;23(10):593-600.
RhoB, a member of the Rho subfamily of small GTPases, mediates diverse cellular functions, including cytoskeletal organization, cell transformation and vesicle trafficking. The thymus undergoes progressive decline in its structure and function after puberty. We found that RhoB was expressed in thymic medullary epithelium. To investigate a role of RhoB in the regulation of thymic epithelial organization or thymocyte development, we analyzed the thymi of RhoB-deficient mice. RhoB-deficient mice were found to display earlier thymic atrophy. RhoB deficiency showed significant reductions in thymus weight and cellularity, beginning as early as 5 weeks of age. The enhanced expression of TGF-β receptor type II (TGFβRII) in thymic medullary epithelium was observed in RhoB-null mice. In addition, the expression of fibronectin, which is shown to be regulated by TGF-β signaling, was accordingly increased in the mutant thymic medulla. Since there is no age-related change of RhoB expression in the thymus, it is unlikely that RhoB in thymic epithelium directly contributes to age-related thymic involution. Nevertheless, our findings strongly support a physiological role of RhoB in regulation of thymus development and maintenance through the inhibition of TGF-β signaling in thymic medullary epithelium.
PMCID: PMC3182298  PMID: 21865151
atrophy; RhoB; thymus; TGF-β
25.  Assessing the Quality of Randomized Controlled Trials Published in the Journal of Korean Medical Science from 1986 to 2011 
Journal of Korean Medical Science  2012;27(9):973-980.
Low quality clinical trials have a possibility to have errors in the process of deriving the results and therefore distort the study. Quality assessment of clinical trial is necessary in order to prevent any clinical application erroneous results is important. Randomized controlled trial (RCT) is a design for evaluate the effectiveness of medical procedure. This study was conducted by extracting the RCTs from the original articles published in the Journal of Korean Medical Science (JKMS) from 1986 to 2011 and conducting a qualitative analysis using three types of analysis tools: Jadad scale, van Tulder scale and Cochrane Collaboration risk of bias Tool. To compare the quality of articles of JKMS, quality analysis of the RCTs published in Yonsei Medical Journal (YMJ) and Korean Journal of Internal Medicine was also conducted. In the JKMS, YMJ and Korean Journal of Internal Medicine, the quantitative increase of RCT presented over time was observed but no qualitative improvement of RCT was observed over time. From the results of this study, it is required for the researchers to plan for and perform higher quality studies.
PMCID: PMC3429837  PMID: 22969240
Randomized Controlled Trial; Journal Article

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