Subclinical Vitamin D Insufficiency in Korean School-aged Children / 대한소아소화기영양학회지

PURPOSE: Recently, vitamin D insufficiency has increased and has been correlated to growth and puberty in children. This study was conducted to find the prevalence of subclinical vitamin D insufficiency and its influence on school-aged children in Korea. METHODS: The subjects of this study were 397 children aged 7 to 15 years who had been tested for 25-OH vitamin D3 among the outpatients of the Department of Pediatrics in Eulji General Hospital from March 2007 to February 2011. Data for age, sex, comorbidities, serum 25-OH vitamin D3, height, weight, body mass index (BMI), and sunlight exposure time were collected before and after 3 months of vitamin D administration, retrospectively. RESULTS: Vitamin D insufficiency was present in 343 (86%) of the subjects. In the vitamin D insufficient group, chronological age was 8.96+/-1.72 years, mean height (z-score [z]) was 0.51+/-1.26, mean BMI (z) was 0.81+/-2.20, and bone age was 10.26+/-1.75 years. In the vitamin D sufficient group, chronological age was 9.61+/-1.77 years, mean height (z) was-0.66+/-0.98, mean BMI (z) was-0.01+/-1.16, and bone age was 9.44+/-2.12 years. A paired t-test showed that three months after vitamin D administration, the mean 25-OH vitamin D3 level in the insufficient group increased to 24.38 +/-10.03 ng/mL and mean BMI (z) decreased to 0.67+/-1.06. CONCLUSION: In Korean school-aged children, vitamin D insufficiency were relatively higher and may be closely related with higher BMI. Insufficient rise of the level of vitamin D after supplementation suggest the new supplementation guidelines, especially for Korean children.

An Adenocarcinoma of Lung with Unusual Very Slow Growth : A case report

The prognosis of lung cancer is very poor. Patients with lung cancer have usually no symptom in early stage or some mild cough, sputum. When patient feel weight loss or dyspnea, majority of patients with lung cancer are advanced stage and inoperable. The growth rate of lung cancer is different according to cell type of tumor and related to prognosis. Generally, tumor. doubling time (TDT) of lung cancer has been known that small cell lung cancer is about 65 days, squamous cell carcinoma is about 90 days, and adenocarcinoma is about 185 days. There has been rarely reported of lung cancer with very fast or very slow growth. The prognosis of a slow growing lung cancer is relatively good but rapidly growing cancer is not. We report a very rare case that surgicallytreated early stage non-small cell lung cancer (adenocarcinoma) with 4-year- TDT without invasion or distant metastasis

Relation of Epidermal Growth Factor Receptor Expression to Goblet Cell Dysplasia in Diffuse Panbronchiolitis / 결핵

BACKGROUND: Diffuse panbronchiolitis(DPB) is a chronic inflammatory lung disease that presents as coughing, copious sputum, exertional dyspnea, which progresses to bronchiectasis. The pathogenesis of bronchiectasis is controlled by inflammatory mediators, which are closely related to mucus hypersecretion, goblet cell dysplasia. In recent studies, the epidermal growth factor receptor(EGFR) system was reported to be associated with this process. It was hypothesized that a relationship exists between goblet cell dysplasia, EGFR expression, and inflammatory mediators produced by neutrophil. METHOD: Alcian blue/periodic acid -Schiff(AB/PAS) stain, MUC5AC, EGFR, CD16 immunohistochemical stain were examined to investigate a role for the EGFR system in a mucus hypersecretion in DPB using the lung biopsy specimens from 13 DPB patients and 6 controls. RESULTS: In the DPB group, the AB/PAS- and MUC5AC-stained areas were 8.31+/-3.36%, 11.46+/-4.68%, respectively. In the control group, the AB/PAS- and MUC5AC-stained areas were 50.5+/-5.77%, 53.3%+/-6.67%, which was significantly larger than in the DPB group (each comparison, p<0.05). The percentage of EGFR expression was 9.54+/-4.95% in the DPB group, but zero in of the control group. The extent of neutrophilic infiltration was 71.92+/-3.71/5HPF in the DPB group and 45.0+/-5.73/5HPF in the control group, which was statistically significant(p=0.002). CONCLUSION: The EGFR system is highly related to goblet cell dysplasia, mucus hypersecretion and neutrophilic inflammation in DPB.

Myxoid Leiomyosarcoma of the Superior Vena Cava Syndrome / 결핵

A 38-year-old woman presented with facial edema with neck vein engorgement for about 45 days. Chest roentgenography showed bulging soft tissue opacities in the right superoanterior mediastinum and a lobulated intraluminal mass was noted in the superior vena cava on the venacavogram. The superior vena cava was incised and the tumor located from the junction of the superior vena cava and internal jugular vein to the right atrial inlet was excised. Grossly, the tumor was myxoid or gelatinous in appearance. A combination of microscopic and immunohistochemical features showed myxoid leiomyosarcoma arising from the wall of the superior vena cava.

Fat embolism syndrome with pulmonary hemorrhage of unknown origin / 결핵

Fat embolism syndrome is a rare but serious complication occurring most of the time in patients with long bone fractures. And it occasionally occurs when patient had underlying disease. For example, pancreatitis, diabetes mellitus, alcoholic liver disease and connective tissue disease can be risk factors. The 44-year old woman visited to the Korea university hospital because of sudden dry cough, blood tinged sputum, and exertional dyspnea. We found petechiae on her anterior chest wall. Chest X-ray and CT showed patchy opacities and multifocal ground-glass opacities in both lung fields. Open lung biopsy demonstrated diffuse pulmonary hemorrhage and intravascular macrovesicular fat bubbles. After conservative management, her symptoms and radiologic findings were significantly improved. We report a case of fat embolism syndrome without any known risk factors.

The detection of circulating breast cancer cells in peripheral blood by reverse transcriptase-polymerase chain reaction

Some circulating cancer cells in the blood play a central role in the metastatic process and may have a major influence on patient progress. Their numbers can be very small and techniques for their detection need to be both sensitive and specific. Polymerase chain reaction (PCR) has been successfully used to detect small numbers of tumor cells in cancer. We used a reverse transcriptase-polymerase chain reaction (RT-PCR) to detect circulating breast cancer cells in venous blood samples before operations and assessed cytokeratin-19 (CK-19) and cytokeratin-20 (CK-20) as target mRNA markers in the blood of healthy donors (n=6) and breast cancer patients (n=30) with American Joint Committee on Cancer stages 0 to IIIa. CK-19 mRNA was expressed in all blood samples of healthy donors and patients. But CK-20 was the only mRNA marker not detected in the blood from healthy donors. Seven of 30 (23%) venous blood isolates of breast cancer patients yielded a CK-20 mRNA with positive results. There was no correlating CK-20 mRNA expression with stage and axillary lymph node status. In conclusion, CK-19 showed no diagnostic value as a mRNA marker in the detection of circulating cancer cells by RT-PCR assay because this was expressed in the blood of healthy donors. CK-20 mRNA was an useful marker to detect circulating cancer cells in breast cancers.

Significance of K-ras mutation, K-ras expression and p53 expression in pancreatic cancer / 한국간담췌외과학회지

BACKGROUND: Though K-ras mutation and aberrant p53 have been considered the event of the oncogenesis of pancreatic adenocarcinoma, it is controversial that these have been attributed to difference of survival in pancreatic adenocarcinoma. We investigated for presence of a K-ras mutation, K-ras expression and p53 expression in carcinogenesis of pancreatic adenocarcinoma. Also their correlation with tumor grade, stage and survival was investigated. METHODS: We examined 48 patients surgically resected, formalin-fixed and paraffin-embedded pancreatic adenocarcinoma. By using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), we detected K-ras mutation at codon 12. An aberrant K-ras and p53 expression was stained using an immunohistochemical staining (IHC) method. RESULTS: Thirty-one of 48 cases (64.6%) showed K-ras mutation. K-ras expression was showed in 68.8% (33/48). p53 expression was showed in 47.9% (23/48). There was no correlation between a presence of K-ras mutation or K-ras expression and tumor grade, lymph node metastasis, clinical stage or survival rate. A positive correlation between p53 expression and clinical stage was found (p0.05). CONCLUSION: Mutation of the K-ras gene and aberrant p53 might play an important role in pancreatic carcinogenesis. But mutation of K-ras gene and K-ras expression is not considered to relate to progression of pancreatic carcinoma. It is suggested that p53 expression seems to be associated with a progression of pancreatic carcinoma.

The Bronchial Biopsies and Steroid Response in Unexplained Chronic Non-Productive Cough / 결핵

BACKGROUND: The purpose of this study was to examine the causes and pathologic process of chronic non-productive cough as an isolated symptom with a normal spirometry and chest radiograph by investigating clinicopathologic findings. METHOD: We studied 25 adults with chronic non-productive cough over a 3-week period with a normal chest radiograph and pulmonary function tests without any other symptoms. Clinical assessment, cough score, chest and sinus radiograph, pulmonary function tests, methacholine challenge, allergic skin prick test, and bronchoscopy for bronchial biopsies were performed. Subjects were then treated with prednesolone 20 to 30 mg/day for 1 to 2 weeks. RESULTS: The experimental group was divided into two subgroups - those infiltrated with eosinophils, and those infiltrated with lymphocytes depending on eosinophil and lymphocyte counts, both of which were respectively higher than those of the control group. Eosinophils infiltrated group had mean numbers of eosinophil of 89.8 cells/mm(2) while control group's mean was 0.4 cells/mm(2)(P=0.005). Lymphocyte infiltrated group was 4 patients whose mean was 84.3 cells/mm(2) with 28.4 cells/mm(2) of control group(P=0.026). In addition, the mean thickeness of the basement membrane of experimental group was 14.20+/-5.20microM in contrast of control group whose mean was 3.50+/-1.37microM(P=0.001). With the methacholine challenge test, 7 of the 21 eosinophil infiltrated subjects were diagnosed with cough asthma; the other 14 with eosinophilic bronchitis. Three subjects with eosinophilic bronchitis were atopic positive(21.4%) with the skin prick test. In the lymphocyte dominant group, all four subjects were diagnosed with lymphocytic bronchitis. Cough score was improved after steroid treatment in 22 of 25 subjects in the experimental group (88.0%). CONCLUSION: These results suggest chronic non-productive cough as an isolated symptom with a normal spirometry and chest radiograph was associated with airway inflammation by eosinophil and lymphocyte infiltration. The causes for chronic non-productive cough were eosinophilic bronchitis, cough variant asthma, and lymphocytic bronchitis(written in frequency). They further suggest that therapeutic treatment with steroids can provide effective symptomatic relief.

Prevalence and clinical significance of abnormal p53 gene in patients with ampullary adenocarcinoma / 대한내과학회지

BACKGROUND: Although abnormalities of p53 gene and their relation to clinicopathologic parameters have been identified in some human malignancies, there is little published data on their prevalence and clinical significance in ampullary adenocarcinoma (AAC). The aim of this study is to determine the prevalence of p53 abnormalities in AAC and to evaluate their relation to clinicopathologic features. METHOD:35 formaline-fixed paraffin-embedded tissues of AAC were examined for detection of p53 abnormalities by both single-strand conformation polymorphism (SSCP) analysis of polymerase chain reaction- amplified DNA fragments corresponding to exons 5-8 and immunohistochemistry (IHC) using monoclonal antibody to p53 protein (Novocastra, DO7), and the association between the p53 abnormalities and clinicopathologic parameters was analyzed. RESULT: In 22.9% of AAC, p53 gene muation was demonstrated by SSCP analysis, mainly at PCR-amplified exon 8 and exon 7. The p53 protein overexpression by IHC was 48.6% of AAC. Six SSCP and IHC-positive (17.2%) cases and 16 normal (45.7%) cases showed concordant results between the methods, although 13 cases (37.1%) showed discordance, including 11 IHC-positive (31.4%) and 2 SSCP-positive (5.7%) cases. Overall, the prevalence of p53 abnormalities was 54.3%. No significant associations between the p53 abnormalities and clinicopathological parameters such as clinical manifestations, histologic differentiation, and tumor stage were observed. CONCLUSION: The p53 abnormalities detected in 55% of AAC are not associated with prognostic factor, suggesting that abnormal p53 gene may play a role in the development of AAC, but not in its invasiveness.

Immunohistochemical and Biochemical Ligand Binding Estrogen Receptor Assays in Breast Cancer and Comparison to the Measured Time

BACKGROUND: The estrogen receptor (ER) in breast cancer specimens has traditionally been assessed using a biochemical ligand binding assay (LBA). Recently, the application of an immunohistochemical method (IHC) for formalin-fixed breast carcinoma tissue has greatly increased. Controversy exists over the accuracy of IHC compared with that of LBA in determining ER. METHODS: Breast-carcinoma tissues were obtained from 247 patients. ER was determined within 1 week or at 4 weeks after surgery by using the traditional LBA and by using IHC with monoclonal antibodies. The ER status was assessed with respect to age, size of tumor, and stage according to the two methods. RESULTS: The concordant rate of ER status was 75% between IHC and LBA. IHC-negative/LBA- positive results occurred in 31 cases (13%) and IHC-positive/LBA-negative were observed in 30 cases (12%). ER-positive cases were more common in older patients. The disconcordant rate was much higher in premenopausal females. There was a significantly lower ER positivity in tumors of larger than 5 cm. ER positivity was significantly lower at 4 weeks compared to within 1 week in both methods, but this did not change the concordance rate between the two methods. CONCLUSIONS: The ER-IHC method appears to be a reasonable substitute for a biochemical ligand binding assay. This is based on a 75% concordance of the method as well as on the findings in the disconcordant cases. The appropriate measured time for ER was within 1 week after the cancer tissues were obtained.

Immunohistochemical Stain of Prohibitin in Various Breast Tumors

The diagnosis of breast disease relies primarily on histopathological diagnosis of hematoxylin-eosin stained specimens. Recently, the histopathological diagnosis has been complemented to an extent by analyses of a growing array of immunohistochemical and molecular markers. Prohibitin is an evolutionarily conserved gene with homologues found in organisms ranging from yeast to man. Prohibitin has anti-proliferous activity and available data suggest a role in such diverse processes as normal cell cycle regulation, replicate senescence, cellular immortalization, and the development of sporadic breast tumors. In this study, the prohibitin protein was immunohistochemically stained in representative samples from 10 patients with fibrocystic diseases, 10 with fibroadenomas, 10 with ductal carcinomas in situ, and 33 with infiltrating ductal carcinomas of the breast. There were weaker expressions throughout the tissue in benign breast diseases, but there was stronger staining in the glandular epithelium of breast cancers than with the stromal components. The epithelial and the stromal prohibitin expressions were elevated in carcinomas in situ and in infiltrating ductal carcinomas. However, the expression was most notable in infiltrating ductal carcinomas. There was no correlation between the prohibitin protein and the histologic grade or the TNM stage in breast cancer(p<0.05). These results show that imunohistochemical staining of prohibitin can be used as a diagnostic biomarker in breast cancer.

Investigation of the Relationship between Interleukin-4 Promoter Polymorphism and Severity of Patients with Bronchial Asthma / 결핵

BACKGROUND: Interleukin-4 plays an important role in pathogenesis of asthma, especially in developing atopy by means of switching B lymphocytes to produce IgE. It has been shown that there is polymorphism in the Interleukin-4 promoter region, transversion of cytosine to thymine at-598 from translation initiation site of IL-4 gene. There has also been quite a few works to reveal the role of the polymorphism of IL-4 gene in patients with asthma. We performed this investigation to determine the role of the polymorphism in the severity of symptoms of patients with asthma. We also examined the frequency and the type of the polymorphism in asthmatics compared with non-asthmatics as well. METHOD: The subjects enrolled in this study were 49 asthmatics and 33 non-asthmatics. All the asthmatics were classified as mild and moderate to severe by the NHLBI/WHO Workshop. DNA from both asthmatics and non-asthmatics was extracted, then performed ARMS(Amplification Refractory Mutation System) as well as RFLP using BsmF1 restriction enzyme in order to confirm the polymorphism of IL-4 gene. RESULTS: There was no significant difference in the occurrence of polymorphism of the IL-4 promoter sequence between asthm and non-asthma groups(P=0.7). Among those with polymorphisms, the number of C/C type was slightly more than C/T type in both asthmatics and non-asthmatics, 26 vs 21 in asthmatics and 18 vs 15 in non-asthmatics, which was, however, insignificant statistically. No significant relationship between the severity of asthma and the polymorphism was found(P=0.7). CONCLUSION: There was no significant difference between the severity of asthma and the IL-4 promoter polymorphism(P=0.709). Interestingly, the frequency of the polymorphism in both asthmatics as well as non-asthmatics was found to be even higher than that occurred in Caucasians. However, no significant difference in the frequency of the polymorphism was found in both groups.

Mercury inhalation poisoning and acute lung injury

Acute mercury inhalation poisoning is a rare cause of acute lung injury. It is usually fatal because of progressive pulmonary failure. We experienced a patient with acute respiratory distress syndrome (ARDS) after illicit use of mercury vapor for hemorrhoid treatment; he developed acute chemical pneumonitis following exposure to mercury vapor. Prompt treatment with corticosteroids and penicillamine for acute chemical pneumonitis was instituted; radiologic pulmonary infiltrates disappeared within a week, but late phase neurologic sequelae and pulmonary interstitial fibrosis progressed.

Eotaxin mRNA Expression in Bronchial Mucosa of Patients with Asthma / 결핵

BACKGROUND: Asthma is a chronic inflammatory disease of the airways characterized by a marked infiltration of ecsinophils in the bronchial mucosa. Asthmatic bronchial muosa produces many factors described as king chernotaetic for inflammatory cells. IL-5, RANTES, and MCP-1 alpha are the chemotactic factors for eosinophils, but their roles are controversiaL Recently eotaxin that is a potent eosinophil chernoattracttnt cytokine was detected in a guinea-pig model of allergic airway inflammation, and human eotaxin was cloned. Eotaxin is a specific chemoattractant for eosinophils, but its role in asthma is not confirmed. We examined the in vivo expression of a,taxin in bronchi of asthmatic patients. METHODS: 11 asthmatics and 2 normal controls were enrolled. All subjects were underwent brcnchcscopy with bronchial biopsies in 2nd or 3rd carina. RNA extraction from biopsy samples was done by acid-guanidium method. Semi-quantitaive RT-PCR was done for evaluation of eotaxin mRNA expression. The extent of eosinophil infiltrartion was evaluated by counting the eosinophils in submucosa in HPF of microscope. RESULTS: Eotaxin mRNA expressed in symptomatic, uncontrolled asthma. Steroid inhibited expression of eotaxin mRNA in asthma. Expression of eotaxin mRNA correlated with eosinohil infiltration in bronchial tissues. CONCLUISON: Expression of eotaxin mRNA increases in uncontrolled asthma and eotaxin is involved in the recruitment of eosinophils.

Usefulness of LIFE in diagnosis of bronchogenic carcinoma / 결핵

BACKGROUND: Although the overall prognosis of patients with lung cancer is poor, highly effective treatment exists for the small subset of patients with early lung cancer(carcinoma in situ/micro- invasive cancer). But very few patients have benefit from them because these lesions are difficult to detect and localize with conventional white-light bronchoscopy. To overcome this problem, a Lung Imaging Fluorescence Endoscopic device(LIFE) was developed to detect and clearly delineate the exact location and extent of premalignant and early lung cancer lesions using differences in tissue autofluorescence. PURPOSE: The purpose of this study was to determine the difference of sensitivity and specificity in detecting dysplasia and carcinoma between fluorescence imaging and conventional white light bronchoscopy. MATERIAL AND METHODS: 35 patients (16 with abnormal chest X-ray, 2 with positive sputum study, 2 with undiagnosed pleural effusion, 15 with respiratory symptom) hale been examined by LIFE imaging system. After a white light bronchoscopy, the patients were submitted to fluorescence bronchoscopy and the findings of both examinations have been classified in 3 categories(class I, II, III). From of all class II and III sites, 79 biopsy specimens have been collected for histologic examination: a comparison between histologic results and white light or fluorescence bronchoscopy has been performed for assessing sensitivity and specificity of the two methods. RESULTS: 1) Total 79 sites in 35 patients were examined. Histology demonstrated 8 normal mucosa, 21 hyperplasia, 23 dysplasia, and 27 microinvasive and invasive carcinoma. 2) The sensitivity of white light or fluorescence bronchoscopy in detecting dysplasia was 60.9% and 82.6%, respectively. 3) The results of. this study showed 70.3 % sensitivity for microinvasive or invasive carcinoma with LIFE system, versus 100% sensitivity for white light in 27 cases of carcinoma. The false negative study of LIFE system was 8 cases(3 adenocarcinoma and 5 small cell carcinoma), which were infiltrated in submucosal area and had normal epithelium. CONCLUSION: To improve the ability to diagnose and stage more accurately, fluorescence imaging may become an important adjunct to conventional bronchoscopic examination because of its high detection rate of premalignant and malignant epithelial lesion. But, it has limitation to detect in submucosal infiltrating carcinoma.

Castleman's Disease of the Lung / 결핵

Castleman's disease is uncommon lymphoproliferative disorder as giant lymph node hyperplasia and angiofollicular lymph node hyperplasia. Multicentric variant of Cagtleman's disease, plasma cell type has been, described that has mort generalized lymph node involvement as well as involvement of other organ systems than localized type. Multicentric plasma cell type is frequently accompanied by systemic manifestations, such as weight loss, lowgrade fever and weakness. But the reported cases of pulmonary parenchymal involvement are rare and have almost consisted of hyalinized ganuloma adjacent 13 a bronchus. We report a patient with Castleman's disease of the lung, pathologically proven interstitial pulmonary involvement.