• Clinical and Experimental Pediatrics
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• v.45 no.2
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• pp.183-191
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• 2002

Purpose : X-linked agammaglobulinemia(XLA) is an immunodeficiency caused by abnormalities in Bruton's tyrosine kinase(Btk), and is characterized by a deficiency of peripheral blood B cells. We studied the cytoplasmic expression of Btk protein and analyzed the Btk gene in peripheral blood mononuclear cells from two siblings and one cousin with XLA, as well as additional family members. Methods : Btk protein expression was analyzed by flow cytometry. Isolation of the coding sequence of the Btk gene was performed by amplification using the reverse transcription-polymerase chain reaction(RT-PCR) technique. Sequence alterations were screened by the single-stranded conformation polymorphism(SSCP) method and characterized by standard sequencing protocols. Results : Cytoplasmic expression of Btk protein in monocytes was not detected in three patients with XLA. In addition, Btk protein analysis clearly showed cellular mosaicism in monocytes from four obligate carriers, findings further supported by SSCP. A single base pair mutation(T to C) in Btk-exon three, which encodes the PH domain, was identified in four XLA patients. A diagnostic sequencing analysis was established to detect heterozygotic pattern in 4 carrier females. Furthermore, we found significant clinical heterogeneity in individuals with the same gene mutation. Conclusion : The implicating genetic alteration provided valuable clues to the pathogenesis of XLA in Korea and the flow cytometric analysis was suggested as a useful tool for rapid detection of XLA patients and carriers. The present study has identified a genetic mutation in the Btk coding region and demonstrated heterogeneity in clinical manifestations among patients with the same mutation. A flow cytometric analysis was found to be informative in establishing a deficiency of Btk protein in both patients and carriers and is recommended as a frontline procedure in the molecular diagnosis and work-up of XLA.

• Clinical and Experimental Pediatrics
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• v.45 no.3
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• pp.339-345
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• 2002

Purpose : The purpose of this study was to evaluate the clinical usefulness of chest high-resolution computed tomography(HRCT) in patients with chronic coughs or persistent wheezing with normal chest X-ray finding. Methods : We reviewed the charts, chest X-rays, and HRCT findings of patients with chronic coughs or persistent wheezing of less than 2 years of age. The records were sourced from the Department of Pediatrics, Inha University Hospital covering the period from July, 1999 to June, 2000. Chronic cough was defined as a cough which was prolonged for more than 3 weeks. Results : The sample consisted of 24 patients(male 15 and female 9, mean age $4.7{\pm}3.8$ months old). Among them, 16 patients showed normal findings(66.7%) and 8 patients showed abnormal (33.3%) in simple chest X-rays. Among 16 patients who had the normal chest X-rays, 13 patients showed abnormal chest HRCT findings(81.3%) such as air space consolidation of the dependent portion(62.5%), bronchiolitis obliterans(12.5%), and bronchopulmonary dysplasia(6.3%). Conclusion : We suggest that the chest HRCT is a useful diagnostic tool in the evaluation of patients with chronic cough or persistent wheezing with normal chest X-ray, especially below 2 years of age.

• Clinical and Experimental Pediatrics
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• v.46 no.12
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• pp.1242-1247
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• 2003

Purpose : Gastroesophageal reflux disease(GERD) is known as one of the most common causes of chronic cough, especially in children. The purpose of this study is to evaluate the efficacy of parameters from proximal esophageal 24-hr pH monitoring through its comparison with those of distal esophageal 24-hr pH monitoring that we generally use for diagnosis of GERD. Methods : We performed chest CT scans to find out the cause of chronic cough in infants with no clinical manifestation suggesting GERD. Then, in case that they had air space consolidation in posterior segment of both upper lobes and superior segment of both lower lobes(dependent position), we performed proximal and distal esophageal 24-hr pH monitoring. Results : The proximal and distal pH monitoring were performed in 17 infants(male 12; female five). The patients with positive pathologic reflux in proximal esophagus were 15 of 17(88.2%) and in distal esophagus were four of 17(23.5%). Reflux index and the total number of reflux episodes were statistically significantly lower in the proximal than in the distal esophagus(P<0.05). There was no correlation between each parameters of proximal and distal esophageal 24-hr pH monitoring. Conclusion : This study suggests that proximal esophageal 24-hr pH monitoring can be used as a very useful diagnostic tool in infants with chronic cough in which there are suspicions that it resulted from aspiration due to GERD.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.17 no.3
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• pp.96-102
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• 2017

Glycogen storage disease type IX (GSD IX) is caused by deficiency of phosphorylase kinase which plays a role in breakdown of glycogen. Mutations in PHKA2 are the most common cause of GSD IX (GSD IXa). Clinical manifestations of GSD IXa include hepatomegaly, elevation of liver enzyme, growth retardation, fasting hypoglycemia, and fasting ketosis. However, the symptoms overlap with those of other types of GSDs. Here, we report Korean familial cases with GSD IXa whose diagnosis was confirmed by targeted exome sequencing. A 4-year old male patient was presented with hepatomegaly and persistently elevated liver enzyme. Liver biopsy revealed swollen hepatocyte filled with glycogen storage, suggesting GSDs. Targeted exome sequencing was performed for the differential molecular diagnosis of various types of GSDs. A hemizygous mutation in PHKA2 were detected by targeted exome sequencing and confirmed by Sanger sequencing: c.3632C>T (p.Thr121Met), which was previously reported. The familial genetic analysis revealed that his mother was heterozygous carrier of c.3632C>T mutation and his 28-month old brother had hemizygous mutation. His brother also had hepatomegaly and elevated liver enzyme. The hypoglycemia was prevented by frequent meals with complex carbohydrate, as well as cornstarch supplements. Their growth and development is in normal range. We suggest that targeted exome sequencing could be a useful diagnostic tool for the genetically heterogeneous and clinically indistinguishable GSDs. A precise molecular diagnosis of GSD can provide appropriate therapy and genetic counseling for the family.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7633-7640
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• 2015

Background: Human papillomavirus (HPV) is the most common sexually transmitted infection worldwide and it is responsible for most cases of cervical uterine cancer. Although HPV infections of the cervix do not always progress to cancer, 90% of cervical cancer cases have been found to be associated with high risk HPV (HR-HPV) infection. HPV DNA testing is widely used, along with Papanicolaou (Pap) testing, to screen for cervical abnormalities. However, there are no data on the prevalence of genotype-specific HPV infections assessed by measuring HPV E6/E7 mRNA in women representative of the Chinese population across a broad age range. Materials and Methods: In the present study, we compared the results with the CervicGen HPV RT-qDx assay, which detects 16 HR-HPV genotypes (Alpha-9: HPV 16, 31, 33, 35, 52, and 58; Alpha-7: HPV 18, 39, 45, 51, 59, and 68; and Alpha-5, 6: HPV 53, 56, 66, and 69), and the REBA HPV-ID assay, which detects 32 HPV genotypes based on the reverse blot hybridization assay (REBA) for the detection of oncogenic HPV infection according to cytological diagnosis. We also investigated the prevalence and genotype distribution of HPV infection with a total of 324 liquid-based cytology samples collected in western Shandong province, East China. Results: The overall HPV prevalences determined by HPV DNA and HPV E6/E7 mRNA assays in this study were 79.9% (259/324) and 55.6% (180/324), respectively. Although the positivity of HPV E6/E7 mRNA expression was significantly lower than HPV DNA positivity, the HPV E6/E7 mRNA assay showed greater specificity than the HPV DNA assay (88.6% vs. 48.1%) in normal cytology samples. The prevalence of Alpha-9 (HPV 16, 31, 33, 35, 52, and 58) HPV infection among these women accounted for up to 80.3% and 76.1% of the high-grade lesions detected in the HPV mRNA and DNA tests, respectively. The HR-HPV genotype distribution, based on HPV DNA and E6/E7 mRNA expression by age group in patients with cytologically confirmed lesions, was highest in women aged 40 to 49 years (35.9% for cytologically confirmed cases, Pearson correlation r value=0.993, p<0.001) for high-grade lesions. Among the oncogenic HR-HPV genotypes for all age groups, there was little difference in the distribution of HPV genotypes between the HPV DNA (HPV -16, 53, 18, 58, and 33) and HPV E6/E7 mRNA (HPV -16, 53, 33, 58, and 18) assays. HPV 16 was the most common HPV genotype among women with high-grade lesions. Conclusions: Our results suggest that the HPV E6/E7 mRNA assay can be a sensitive and specific tool for the screening and investigation of cervical cancer. Furthermore, it may provide useful information regarding the necessity for early cervical cancer screenings and the development of additional effective HPV vaccines, such as one for HPV 53 and 58. Additionally, gaining knowledge of HPV distribution may also inform us about ecological changes in HPV after the vaccination.

• Tuberculosis and Respiratory Diseases
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• v.49 no.3
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• pp.353-364
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• 2000

Background : Bronchoscopy is a useful diagnostic tool, for accurate localization of the bleeding site and the management of hemoptysis. However, there is some controversy about the optimal timing of bronchoscopy. Method : To determine the optimal timing of bronchoscopy in hemoptysis, we reviewed the medical records of 118 patients and analyzed the following relationships amongst simple chest PA findings, namely, the duration and amount of hemoptysis, and the timing of bronchoscopy retrospectively. Results : The major causes of hemoptysis were active tuberculosis(28.8%), inactive tuberculosis(10.2%), bronchiectasis(17.0%), lung cancer(7.6%), and aspergilloma(7.6%). Localization of the bleeding focus by bronchoscopy was possible in 87.5% (21/24 cases) during active bleeding, and it was possible in 40.4% after bleeding had stopped(p<0.05). The localization rate of bleeding focus was 59.8% when the chest PA showed certain abnormalities, but it decreased to 27.8% when the chest PA finding was normal(p<0.05). When chest PA showed diffuse abnormalities or its finding was normal, the localization rate of bleeding focus significantly increased if bronchoscopy was performed during bleeding or within 48 hours of the cessation of active bleeding. The localization rate was higher as the amount of hemoptysis became larger(p<0.05). The localization rate of early bronchoscopy(during bleeding or within 48 hours of the cessation of active bleeding) was significantly higher when the duration of hemoptysis was less than 1 week, but there was no advantage if the duration was 1 week or longer. Early bronchoscopy was also necessary to localize the bleeding focus for surgical resection in 4 patients, and the bronchoscopy itself was therapeutic in 1 patient whose bleeding was successfully managed with thrombin-application via bronchoscope. Conclusion : It is concluded that flexible bronchoscopy is useful at not only localizing the bleeding focus but also in preparing a therapeutic plan, and early bronchoscopy is more favorable in hemoptysis.

• Tuberculosis and Respiratory Diseases
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• v.53 no.6
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• pp.612-618
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• 2002

Background : Bronchoscopy is an important diagnostic and a therapeutic tool in chest medicine. However, most patients feel that a bronchoscopy is an unpleasant procedure, and it is important to sedate the patients appropriately, particularly where repetitive examinations are required. Midazolam is a sedative drug with amnestic qualities and a rapid 2 hour half-life. This study have attempted to determine the safety, appropriate dosage, and the effect of midazolam premedication in patients who underwent a bronchoscopy. Methods : One hundred and eighty consecutive patients undergoing bronchoscopy were enrolled in this study. The patients received a midzolam doses of 0.03 mg/kg, 0.06 mg/kg, or a placebo. An additional dose of lidocaine, the total number of coughs, and the duration of the procedures were recorded with monitoring the the blood pressure, heart rate, and oxygen saturation. The level of satisfaction was assessed by the patient, bronchoscopist, and the nurse. Results : The blood pressure, pulse rates, oxygen saturation, number of coughs, lidocaine dose, and procedure time in the 3 groups were similar. There was a trend for the midazolam 0.03 mg/kg group to satisfy bronchoscopists more than the other two groups. The nurses' acceptability was lower in the midazolam 0.06 mg/kg group than the other groups. The patients' acceptablity was greater in both the midazolam 0.03 mg/kg and 0.06 mg/kg groups than in the control group. Conclusion : Sedation with low doses of intravenous midazolam is a safe technique for fiberoptic bronchoscopy with a low morbidity and high acceptable to patients and bronchoscopists.

• Clinical and Experimental Pediatrics
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• v.53 no.4
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• pp.519-524
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• 2010

Purpose : To determine the efficacy of the N-terminal fragment of B-type natriuretic peptide (NT-proBNP) as a useful diagnostic method in children with incomplete Kawasaki disease (KD). Methods : Ninety-six patients who were diagnosed as having KD between January 2008 and June 2009 were enrolled in the study. American Heart Association recommendations for diagnosis were used, and patients were divided into the complete KD and incomplete KD groups. Blood tests including NT-proBNP were performed on admission day. Nineteen patients who had other febrile diseases other than KD were enrolled as control. Results : Thirty-three patients (34%) had incomplete KD. Change in the lips and oral cavity and conjunctivitis were the most common clinical features, but their frequency was lower than complete KD (76% vs 98%, 76% vs 90%). Patients with incomplete KD exhibited significantly higher NT-proBNP level than that of control ($1,407.7{\pm}1633.5pg/mL$ vs $126.2{\pm}135.5pg/mL$, $P$<0.001). An NT-proBNP cutoff value of 158 pg/mL provided a sensitivity of 81% and a specificity of 74% for diagnosis of incomplete KD. Conclusion : NT-proBNP assay can be clinically useful for the diagnosis of incomplete KD, if the patient has persistent fever, change in the lips and oral cavity, and conjunctivitis, and if the patient with those symptoms is suspected to have incomplete KD.

• Journal of environmental and Sanitary engineering
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• v.13 no.1
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• pp.123-134
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• 1998

The study was performed to investigate the differences among various evaluation criteria for noise-induced hearing loss(NIHL). The subjects were 100 workers who had received detailed audiometric examinations after the periodic annual examination for hearing loss. The evaluation criteria included were as follows: The criterion I was NIHL of 50dB or greater at 4,000Hz in either ear which is one of the legal requirements for determining occupational hearing loss in Korea. The criterion II was NIHL of 40dB or greater by 4-divided classification(a+b+c+d/4 at 500Hz(a), 1,000Hz(b), 2,000Hz(c), 4,000Hz(d)) which is also one of the legal requirements for determining occupational hearing loss in Korea. The criterion III was NIHL of 31dB of greater by 6-divided classification(a+2b+2c+d/6) which is the workers' compensation standard. The criterion IV was NIHL of 40dB or greater by 6-divided classification(a+2b+2c+d/6), the criterion used to prohibite workers to be employed in the noisy workplace. The criterion V was NIHL of 40dB or greater by 3-divided classification(a+b+c/3) which is the guideline of the Japanes Labour Department. The results were as follows; 1. The percentage of workers with NIHL by the criterion I was the highest(96%) and covered all workers with NIHL diagnosed by other criteria. Therefore, this criterion was the most sensitive one for early detection of NIHL among various evaluation criteria. 2. The percentage of workers with NIHL by the criterion II was 29% of the subjects, but all of them could be diagnosed as having NIHL by the criterion I and 33.1% of the NIHL by the criterion III could not be covered by the criterion II. Thus, this criterion was not considered suitable as an initial step for determining occupational hearing loss. 3. The percentage of workers with NIHL by the criterion III was 45% of the subjects. This percentage was 46.9% of the NIHL by the criterion I and was estimated to cover 3.6% of all noise exposed workers. 4. The percentage of workers with NIHL by the criterion IV was 28% of the subjects, but 37.8% of the NIHL by the criterion III and 70.8% of the NIHL by the criterion I were not covered by the criterion. Therefore, these workers could have been employed in the noisy workplaces. 5. Employed relocation which was one of the post management methods was an option in the criterion I in Korea and in the criterion V in Japan. The number of NIHL by the criterion I was 6.7times greater than that by the criterion V. Thus, although employee relocation was not used exclusively, many more workers with NIHL could have been relocated. In conclusion, this study revealed that the criteria being used for managing occupational hearing loss showed a lack uniformity among them. In addition, since these criteria are all relied on the total threshold shifts caused by the noise exposure at the time of hearing test with no consideration given to the past noise exposure history nor age, it can be said that they are not an effective tool for occupational hearing loss management. Since legal requirements are usually followed after being diagnosed as having NIHL, it is recommended that a uniform diagnostic criterion should be used to minimize confusion. Pre-employment hearing tests should also be utilized so as to managing occupational hearing loss after employment rather than being used as a legal roadblock of prohibiting workers with mild hearing loss from being employed. Thus, what is needed is an establishment of a rational criterion for occupational hearing loss management rather than for legal requirements.

• Radiation Oncology Journal
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• v.19 no.1
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• pp.34-39
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• 2001

Purpose : It is not common to evaluate the response of the fractionated stereotactic radiotherapy (SRT) to primary hepatoma as compared with conventional radiotherapy. The purpose of the study was to take the preliminary result on the clinical trial of primary hepatoma by SRT. Materials and Methods : From July 1999 to March 2000, thirty three patients were hospitalized in the St. Mary's Hospital, and treated with SRT for extracranial tumors. Among them, 13 patients were diagnosed to primary hepatoma and then applied by frameless SRT using 6 MV linac accelerator. There were 12 male and 1 female patients. They had the age of $ 44\~66$ year old (median : 59) and the tumor size of $10\~825\;cc$ (median : 185 cc). SRT was given to them $3\~5$ fractions a week (5 Gy/fraction, $90\%$ isodose line) for $2\~3$ weeks. Median dose of SRT was 50 Gy and the range was $30\~50\;Gy$. Results : Follow-up period ranged from 3 months to 13 months with median of 8 months. After treating SRT to thirteen patients with primary hepatoma, the response of the tumor was examined by abdominal CT : they are classified by 1 complete regression $(7.7\%)$, 7 partial regression $(53.8\%)$, 4 minimal regression $(30.8\%)$, 1 stable disease $(7.7\%)$. The positive responses more than partial remission were 8 patients $(61.5\%)$ after the treatment. The level of serum alpha-fetoprotein (AFP) after the treatment as compared with pretreatment had been $92.3\%$ decreased. There was no severe complication except dyspepsia $84.6\%$, mild nausea $69.2\%$, transient decreased of hepatic function $15.4\%$ and fever $7.7\%$. Conclusion : SRT to the patients with primary hepatoma was potentially suggested to become the safe and more effective tool than the conventional radiotherapy even though there were relatively short duration of follow-up and small numbers to be tested.