• Journal of The Korean Society of Inherited Metabolic disease
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• v.23 no.1
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• pp.25-30
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• 2023

Leigh syndrome is a rare progressive neurodegenerative mitochondrial disorder with clinical and genetic heterogeneity. Recently, balletic IARS2 variants have been identified in a number of patients presenting broad clinical phenotypes from Leigh and West syndrome to a rare syndrome CAGSSS characterized by cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia syndrome (OMIM#616007). We describe a child with Korean Leigh syndrome with urologic manifestations resulting from a compound heterozygote mutation in IARS2. A 5-year-old girl visited the emergency room with a complaint of abdominal pain accompanied by abdominal distension. Abdominal-pelvic CT showed a markedly distended urinary bladder without definite obstructive lesions. She was diagnosed with neurogenic bladder dysfunction based on a urodynamic study. She had global delayed development due to neurologic regression after 6 months of age and a history of bilateral cataract surgery at the age of 2 years. Her brain magnetic resonance imaging showed symmetrically increased signal intensities in the bilateral putamen and caudate nuclei with diffuse cerebral atrophy. No gene variants were identified through whole-mitochondrial genome analysis. Whole exome sequencing was performed for diagnosis, and compound heterozygous pathogenic variants were identified in IARS2: c.2446C>T (p. Arg816Ter) and c.2450G>A (p. Arg817His). To the best of our knowledge, this is the first case report of bladder dysfunction manifestation in a patient with IARS2-related Leigh syndrome. Thus, it broadens the clinical and genetic spectrum of IARS2-associated diseases.

• Childhood Kidney Diseases
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• v.2 no.1
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• pp.14-19
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• 1998

Purpose : Hypocalcemia is one of the major causes of convulsion in infants. The causes of hypocalcemia are hypoparathyroidism, deficiency and metabolic abnormalities of vitamin D, or increased uptake of inorganic phosphorous, etc. We analyzed the causes, symptoms and signs, treatment, and clinical courses of hypocalcemia as, recently, there were many clinical experiences of hypocalcemic infants under age of 6 months in the department of pediatrics, Kyungpook University Hospital. Objects and Methods : The authors observed 11 infants with hypocalcemia who had been admitted to the department of pediatrics, Kyungpook University Hospital, during the period of February 1992 to April 1997. Various clinical and laboratory data concerning causes, clinical courses and treatment of hypocalcemia were analyzed retrospectively Results : (1) The sex incidence revealed male predominance with male to female ratio 4.5 : 1. The mean age at onset of symptoms was $2.2{\pm}1.1$ months old. (2) The causes of hypocalcemia were vitamin D deficiency in 8 cases and excessive inorganic phosphate intake in 3 cases. (3) All eleven patients manifestated convulsion which was generalized tonic-clonic in 9, and focal clonic in 2 cases. (4) Serum calcium concentrarion increased from $6.3{\pm}0.9$ mg/dL to $9.9{\pm}1.7$ mg/dL after therapy of $1,25(OH)_{2}D_{3}$ with or without calcium(P=0.0008), and serum ALP concentration decreased from $1,418{\pm}864$ U/L to $772{\pm}503$ U/L (P=0.0112). Serum iPTH levels were high in all 11 patients initially. All showed decreased $25(OH)D_3$ levels initially. (5) All patients were treated successfully with $1,25(OH)_{2}D_{3}$ and/or calcium supplement. Conclusions : Vitamin D deficiency should be considered as one of the causes of hypocalcemia even in formula(known as vitamin fortified) feeding infants. Fortunately, they were successfully treated with $1,25(OH)_{2}D_{3}$.

• The Korean Journal of Nuclear Medicine
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• v.37 no.6
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• pp.374-381
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• 2003

Purpose: Determining an appropriate thresholding is crucial for PDG PET analysis since strong control of Type I error could fail to find pathological differences between eariy Alzheimer' disease (AD) patients and healthy normal controls. We compared the SPM results on FDG PET imaging of early AD using uncorrected p-value, random-field based corrected p-value and false discovery rate (FDR) control. Materials and Methods: Twenty-eight patients ($66{\pm}7$ years old) with early AD and 18 age-matched normal controls ($68{\pm}6$ years old) underwent FDG brain PET. To identify brain regions with hypo-metabolism in group or individual patient compared to normal controls, group images or each patient's image was compared with normal controls usingthe same fixed p-value of 0.001 on uncorrected thresholding, random-field based corrected thresholding and FDR control. Results: The number of hypo-metabolic voxels was smallest in corrected p-value method, largest in uncorrected p-value method and intermediate in FDG thresholding in group analysis. Three types of result pattern were found. The first was that corrected p-value did not yield any voxel positive but FDR gave a few significantly hypometabolic voxels (8/28, 29%). The second was that both corrected p-value and FDR did not yield any positive region but numerous positive voxels were found with the threshold of uncorrected p-values (6/28, 21%). The last was that FDR was detected as many positive voxels as uncorrected p-value method (14/28, 50%). Conclusions FDR control could identify hypo-metaboiic areas in group or individual patients with early AD. We recommend FDR control instead of uncorrected or random-field corrected thresholding method to find the areas showing hypometabolism especially in small group or individual analysis of FDG PET.

• The Korean Journal of Nuclear Medicine
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• v.37 no.2
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• pp.94-102
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• 2003

Purpose : Cerebral blood flow (CBF) reactivity to acetazolamide (ACZ) is useful to select patients with hemodynamic failure. However, it is still a matter of speculation that varying degrees of regional CBF increases after ACZ administration represent the severity or stage of regional hemodynamic failure as assessed by positron emission tomography (PET). We studied to elucidate whether ACZ challenge $^{123}I-IMP$ brain single photon emission tomography (SPECT) can accurately grade the seventy of regional hemodynamic failure. Materials and Methods: Eighteen patients (M: 16, F: 2, average age: 61 years) with unilateral occlusive disease of the internal carotid artery or the trunk of the middle cerebral artery (MCA). Patients undewent $^{123}I-IMP$ brain SPECT study with acetazolamide challenge and PET study was carried out within 2 weeks before and after SPECT study. Five healthy volunteers with a mean age of 48 years (range: 28-73 yr, M: 3, F: 2) underwent PET studies to determine normal values. In SPECT study, an asymmetry index (Al)-the percentage of radioactivity of region of interest (ROI) in the occlusive cerebrovascular lesion to the contralateral homologous ROI-was used for numerical evaluation of relative $^{123}I-IMP$ distribution. In PET study, regional CBF, oxygen extraction fraction (OEF), cerebral metabolic rate of oxygen ($CMRO_2$) and cerebral blood volume (CBV) values were measured with $^{15}O-labeled$ gas inhalation method and the values were used for comparison with Al (Al during acetazolamide challenge-Al of basal study) on the SPECT study. ROls were classified by severity into three groups (normal, stage I and stage II). Results: Mean values of Al in areas with normal, stage I and stage II hemodynamic failure were $6.25{\pm}7.77%\;(n=107),\;-10.38{\pm}10.41%\:(n=117)\;and\;13.30{\pm}10.51%\;(n=140)$, respectively. Al significantly differed with each groups (p<0.05). Correlation between Al and CBF, OEF and CBV/CBF in hemisphere with occlusive cerebrovascular lesion was 0.20 (p<0.01), -0.28 (p<0.01) and -0.28 (p<0.01), respectively. Conclusion: We concluded that $^{123}I-IMP$ brain SPECT with acetazolamide challenge could determine the severity ad stage of regional hemodynamic failure as assessed by PET.

• Journal of Chest Surgery
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• v.37 no.8
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• pp.691-701
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• 2004

Background: Tissue hypoxia is a characteristic of many human malignant neoplasms, and hypoxia inducible factor-1 (HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increased oxygen delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-1 a has been reported in many human malignancies, but in esophageal squamous cell carcinoma, the influence of HIF-1 a on tumor biology, including neovascularization, is not still defined. Material and Method: The influence of HIF-1 a expression on angiogenic factors, correlation between the tumor proliferation and HIF-1 a expression, interaction of HIF-1 a expression and p53, and correlation between HIF-1 a expression and clinicopathological prognostic parameters were investigated, using immunohistochemical stains for HIF-1 a, VEGF, CD34, p53, and Ki-67 on 77 cases of resected esophageal squamous cell carcinoma. Result: HIF-1 a expression in cancer cells was found in 33 of 77 esophageal squamous cell carcinoma cases. The 33 cases (42.9%) showed positive stain for HIF-1 a. High HIF-1 a expression was significantly associated with several pathological parameters, such as histologic grade (p=0.032), pathological TMN stage (p=0.002), the depth of tumor invasion (p=0.022), regional lymph node metastasis (p=0.002), distant metastasis (p=0.049), and lymphatic invasion (p=0.004). High HIF-1 a expression had significant VEGF immunoreactivity (p=0.008) and Ki-67 labeling index (p<0.001), but was not correlated with microvascular density within tumors (p=0.088). The high HIF-1 a expression was correlated with aberrant p53 accumulation with a marginal significance (p=0.056). The overall 5-year survival rate was 34.9%. The survival rate of patients with a high HIF-1 a expression was worse than that of patients with low-expression tumors (log-rank test, p=0.0001). High HIF-1 a expression was independent unfavorable factors although statistical significance is marginal in multivariate analysis. Conclusion: It is suggested that (1) high HIF-1 a expression in esophageal squamous cell carcinoma is associated with tumor hypoxia, or with genetic alteration in early carcinogenesis and progressive stages, (2) high HIF-1 a expression may be associated with intratumoral neovascularization through HIF-VEGF pathway, and (3) high HIF-1 a expression is associated with poor prognosis in patients with esophageal squamous cell carcinoma and may playa role as biomarker for regional lymph node metastasis.

• The Korean Journal of Nuclear Medicine
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• v.31 no.1
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• pp.90-101
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• 1997

The purpose of this study is to evaluate the diagnostic accuracy of various quantitative indices for the differentiation of benign from malignant primary soft tissue tumors by FDG-PET. A series of 32 patients with a variety of histologically or clinically confirmed benign (20) or malignant (12) soft tissue lesions were evaluated with emission whole body (5min/bed position) PET after injection of [$^{18}F$]FDG. Regional 20min transmission scan for the attenuation correction and calculation of SUV was performed in 16 patients (10 benign, 6malignant) followed by dynamic acquisition for 56min. Postinjection transmission scan for the attenuation correction and calculation of SUV was executed in the other 16 patients (10 benign, 6 malignant). The following indices were obtained. the peak and average SUV (pSUV, aSUV) of lesions, tumor-to-background ratio acquired at images of 51 min p.i. ($TBR_{51}$), tumor-to-background ratio of areas under time-activity curves ($TBR_{area}$) and the ratio between the activities of tumor ROI at 51 min p. i. and at the time which background ROI reaches maximum activity on the time-activity curves ($T_{51}/T_{max}$). The pSUV, aSUV, $TBR_{51}$, and $TBR_{area}$ in malignant lesions were significantly higher than those in benign lesions. We set the cut-off values of pSUV, aSUV, $TBR_{51},\;TBR_{area}$ and $T_{51}/T_{max}$ for the differentiation of benign and malignant lesions at 3.5, 2.8, 5.1, 4.3 and 1.55, respectively. The sensitivity, specificity and accuracy were 91.7%, 80.0%, 84.4% by pSUV and aSUV, 83.3%, 85.0%, 84.4% by $TBR_{51}$, 83.3%, 100%, 93.8% by $TBR_{area}$ and 66.7%, 70.0%, 68.8% by $T_{51}/T_{max}$. The time-activity curves did not give additional information compared to SUV or TBR. The one false negative was a case with low-grade fibrosarcoma and all four false positives were cases with inflammatory change on histology. The visual, analysis of FDG-PET also detected the metastatic lesions in malignant cases with comparable accuracy In conclusion, all pSUV, aSUV, $TBR_{51}$, and $TBR_{area}$ are useful metabolic semi-quantitative indices with good accuracy for the differentiation of benign from malignant soft-tissue lesions.

• Journal of Chest Surgery
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• v.33 no.12
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• pp.941-947
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• 2000

Background: Central nervous system complication after coronary artery bypass grafting(CABG) is one of the major prognostic determinants and the use of the cardiopulmonary bypass(CPB) may increase the incidence of this devastating complication. In this study, the outcomes after off-pump CABG were studied and compared with those following the conventional CABG using CPB. Material and Method: Among the consecutive isolated CABG's performed in SNUH during Feb. 1995 and Jun. 1999, 338 coronary artery bypass grafting were divided into two groups. 223 patients underwent CABG using the CPB(Group I), and 115 patients underwent CABG without CPB(OPCAB)(Group II). All patients enrolled in this study received extensive preoperative examinations including thorough neurologic examination before and after surgery, transcranial doppler study, carotid duplex ultrasonography, and magnetic resonance angiography if necessary. Central nervous system(CNS) complications were defined as stroke, seizure, metabolic or hypoxic encephalopathy and transient delirium after surgery. Result: There were 61 cases(27.3%) who developed postoperative CNS complication in Group I, whereas 8 cases(7.0%) of CNS complications developed postoperatively in group II(p<0.05). Statistically significant predictors of postoperative CNS complications in group I were age and the use of cardiac assist devices perioperatively. Conclusion: This study suggested that omitting the use of CPB in CABG resulted in significant decrease of the postoperative CNS complications. OPCAB should be more widely applied especially to the elderly who have preexisting cerebrovascular disease.

• Korean Journal of Psychosomatic Medicine
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• v.26 no.2
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• pp.188-193
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• 2018

Objectives : Clozapine is a widely prescribed antipsychotic drug for schizophrenia and is known to increase the risk of cardiovascular disease due to its metabolic side effects. However, little is known about the effect of clozapine on the platelet activation, another important factor in the development of cardiovascular disease. In this study, we tried to investigate the effect of clozapine on platelet activity in patients with schizophrenia by comparing the mean platelet component (MPC) values before and after the clozapine administration. Methods : A retrospective review of medical records of patients with schizophrenia, who newly started clozapine treatment from September 1st, 2003 to April 30th, 2007 at the Department of Psychiatry, Konyang University Hospital in Republic of Korea was performed. The final statistical analysis included 14 participants. Bayer ADVIA $120^{(R)}$ system was used to measure MPC. Results : Among the 14 participants, five subjects were males (28.60%), and ten subjects were females (71.40%). The mean age of participants was $37.50{\pm}11.64years$. Average of duration of illness was $91.00{\pm}93.96months$, with the mean dosage of clozapine taken by participants at the time of the last blood test was $337.50{\pm}109.52mg$. The mean MPC measurement before and after receiving clozapine was $26.12{\pm}2.22g/dL$ and $25.14{\pm}2.08g/dL$ respectively. Wilcoxon signed rank test showed that there was a statistically significant decrease in MPC levels after clozapine administration (V=16, p=0.024). Conclusions : Decreased MPC levels after clozapine administration implies that clozapine may increase platelet activation which could have an adverse effect on the occurrence of thromboembolic disease. Our findings also suggest that careful monitoring of the risk factors of cardiovascular diseases, such as platelets activity, is necessary when administering clozapine.

• Journal of Digital Convergence
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• v.12 no.9
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• pp.237-244
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• 2014

Pathogenic fungal infections are predominantly occurred in patients with severe immune or metabolic defects. In the present study, we aimed to investigate the last five years (2007~2011) 190,250 cases clinical specimens of yeast 3,487 results that had shown positive culture and to look at the significance of regional difference and identify relationship between provide the characteristics about association between clinical isolates and gender, age, and type of specimens. The yearly strain-specific isolation frequency of yeast separated was 1,925(55.2%) for C. albicans the largest of them. All kinds of clinical specimen was 1,495(42.9%) in urine, 998(28.6%) in sputum. Strain-specific gender differences in C. albicans for males was 1,177(57.8%) of the total of 2,037 and 748(51.6%) of 1,450 and as for age, those between 70 and 79 were the largest with 639(55.1%) of the 1,925 strain. In this study, well presented the general characteristics of pathogenic yeast seen in diverse specimens. This limitation has been implemented in a single area, Future research is expected to examine more on nationwide distribution chart, dynamic characteristics and future antibiotic sensitivity.

• Journal of Society of Preventive Korean Medicine
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• v.11 no.2
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• pp.41-70
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• 2007

The purpose of this study was to identify a tendency in patients who seek oriental medical service and factors influencing patient satisfaction. The study was conducted with 1,520 residents of a community during the period from February 5, 2005 through June 30, 2005 using a questionnaire. This study results are summarized as follows : 1. Of subjects who sought oriental medical service, 66.2% had musculoskeletal disorder and connective tissue disease, 18.9% had digestive tract disease, 16.4% had respiratory disease, 8.2% had endocrinemetabolic disease, 7.5% had circulatory disease and the remaining subjects had other diseases(p<0.001). 2. Of subjects who sought oriental medical service for the treatment of musculoskeletal disorder, 84.9% preferred acupuncture. Of those who had digestive tract diseases, 47.0% preferred packaged herbal medicine. Of those who had respiratory disease, 63.0% preferred packaged herbal medicine. 3. Acupuncture was the most often sought by subjects with musculoskeletal disorder. Packaged herbal medicine was sought by subjects with respiratory disease, digestive tract disease, endocrine-metabolic disease or circulatory disease. Tablet-type herbal medicine was sought by subjects with musculoskeletal disorder or digestive tract disease. Combined therapy was sought by subjects with musculoskeletal disorder, digestive tract disease, hematopoietic disease or immune disorder. 4. The level of satisfaction with oriental medical service was higher in subjects with circulatory disease, subjects with digestive tract disease, subjects with neurological disorder and subjects with musculoskeletal disorder in descending order. Of total subjects, 39.4% experienced side effects of oriental medical care, 38.1% experienced side effects of herbal medicine. About 51.9% considered the price of herbal medicine costly while 23.2% considered it reasonable. 5. Subjects' knowledge of herbal medicine was measured as $29.2{\pm}3.83$ out of 42 scores or 69 out of 100 points, indicating a low knowledge level. Subjects' knowledge was influenced by occupation, religion, side effects, sex, age, residence area, the type of insurance. These variables explained 15.2% of the variance. 7. Of total subjects, 56.8% were satisfied with oriental medical service. Patient satisfaction varied with occupation, religion, the type of insurance, health state and treatment outcomes. These variables explained 37.3% of the variance. Conclusion : The majority of subjects were satisfied with oriental medical service. However, oriental medical care are not widely used to treat all kinds of diseases while its use skews to a small categories of diseases. It is therefore necessary for the government and oriental medical service providers to develop new therapy approaches for the treatment of a broader range of diseases.