The Her-2/neu protooncogene encodes a transmembrane tyrosine kinase that is structurally homologous to the receptor for epidermal growth factor. Its amplification and overexpression are associated with poor prognosis in breast cancer patients. Neu differentiation factor is a ligand for Her-2/neu protooncogene and was detected in ras-transformed rat fibroblasts. Heregulin (human homologue of neu differentiation factor) is a 44-kilodalton glycoprotein that stimulates tyrosine phosphorylation and induces growth arrest or stimulation and differentiation in human breast cancer cell lines. In this study we examined the expression of heregulin mRNA by nested reverse transcription (RT) PCR with fresh tissue, Her-2/neu protein, ICAM-1 and steroid receptors by immunohistochemistry, and DNA ploidy pattern by flow cytometry with paraffin-embedded tissue in invasive breast carcinoma. We compared the data with nodal status, lymphovascular invasion, steroid receptor status and DNA ploidy pattern. For RT-PCR to heregulin mRNA, 38 cases of fresh breast cancer tissue were obtained. Total 68 cases of invasive breast carcinoma tissue were fixed in formalin, which were used for routine histology, immunohistochemistry and flow cytometry. The results are as follows; 1) Heregulin mRNA was expressed in 86.1% of patients with invasive breast carcinoma and 100% of patients with benign breast lesion using nested RT-PCR analysis. 2) Her-2/neu protein was overexpressed in 50.0% of tumors using immunohistochemistry. The expression of Her-2/neu protein was significantly correlated with high counts of lymph nodes with metastasis (p<0.05), and high nuclear grade (p<0.05). 3) Her-2/neu protein overexpression was significantly correlated with a high DNA index(p<0.05). All of the tumors showing Her-2/neu protein overexpression and no heregulin mRNA expression revealed near tetraploid DNA content. However, both Her-2/neu overexpression and heregulin mRNA expressing tumors revealed near tetraploidy in 38.9% and diploidy in 50.0%. Based on these results, heregulin mRNA expression rate was 86.1% in human invasive breast carcinoma. Her-2/neu protein overexpression is associated with high positive lymph node number and DNA index. Statistically significant reverse correlation with lymph node metastasis is not present.
Animals ; Breast Neoplasms* ; Breast* ; Cell Line ; Diploidy ; DNA* ; Epidermal Growth Factor ; Fibroblasts ; Flow Cytometry ; Formaldehyde ; Glycoproteins ; Humans* ; Immunohistochemistry ; Intercellular Adhesion Molecule-1 ; Lymph Nodes ; Neoplasm Metastasis* ; Neuregulin-1* ; Phosphorylation ; Ploidies* ; Polymerase Chain Reaction ; Prognosis ; Protein-Tyrosine Kinases ; Rats ; Receptors, Steroid ; Reverse Transcription ; RNA, Messenger* ; Tetraploidy ; Tyrosine

OBJECTIVE: Several abbreviated versions of the Alcohol Use Disorder Identification Test (AUDIT) have been developed and used widely in clinical settings. This paper provides evidence supporting the use of abbreviated versions of AUDIT by comparing the utility of various abbreviated versions and determining the cut-off values for the population of South Korea. METHODS: Data were obtained from the 4th to 6th Korean National Health and Nutrition Examination Surveys. After calculating the whole AUDIT score, the cut-off value of at-risk drinking proposed by the World Health Organization was applied and the study sample was divided into normal and at-risk drinking groups. Receiver operating characteristic curves were drawn for the AUDIT-3rd question (Q3) alone, AUDIT-quantity and frequency (QF), AUDIT-consumption (C), AUDIT-4, and AUDIT-primary clinic (PC), and the optimal cut-off values were obtained for each group. RESULTS: A total of 46,450 subjects were analyzed. The at-risk drinking group comprised 29.2% of all subjects. The area under the receiver operating characteristic curve (AUROC) of the abbreviated versions of AUDIT increased from 0.954 to 0.991 as the number of questions was increased from one to four. The differences in the AUROC between the abbreviated versions of AUDIT were statistically significant. The most appropriate cut-off values for AUDIT-Q3 alone, AUDIT-QF, AUDIT-C, AUDIT-4, and AUDIT-PC for adults over age 19 were 2, 4, 5, 6, and 4 points, respectively. CONCLUSION: As the number of items analyzed increased from one to four, the AUROC increased to a statistically significant level. The cut-off values for the abbreviated versions of AUDIT were similar in South Korea to other countries.
Adult ; Alcohol-Related Disorders ; Alcoholism ; Drinking ; Humans ; Korea ; Nutrition Surveys* ; ROC Curve ; World Health Organization

OBJECTIVE: Several abbreviated versions of the Alcohol Use Disorder Identification Test (AUDIT) have been developed and are widely used in clinical settings. In this study, we provide evidence supporting the use of abbreviated versions of AUDIT by comparing the utility of various abbreviated versions and determining cut-off values for the population of South Korea. METHODS: Data were obtained from the 4th to 6th Korean National Health and Nutrition Examination Surveys. After calculating the whole AUDIT score, we applied the cut-off value of at-risk drinking proposed by the World Health Organization and divided the study sample into normal and at-risk drinking groups. Receiver operating characteristic curves were drawn for AUDIT-3rd question (Q3) alone, AUDIT-quantity and frequency (QF), AUDIT-consumption (C), AUDIT-4, and AUDIT-primary clinic (PC), and optimal cut-off values were obtained for each group. RESULTS: A total of 46,450 subjects were analyzed. The at-risk drinking group comprised 29.2% of all subjects. The area under receiver operating characteristic curve (AUROC) of the abbreviated versions of AUDIT increased from 0.954 to 0.991 as the number of questions increased from one to four. The differences in AUROC between the abbreviated versions of AUDIT were statistically significant. The most appropriate cut-off values for AUDIT-Q3 alone, AUDIT-QF, AUDIT-C, AUDIT-4, and AUDIT-PC for adults over age 19 were 2, 4, 5, 6, and 4 points, respectively. CONCLUSION: As the number of items analyzed increased from one to four items, the AUROC increased to a statistically significant level. Cut-off values for abbreviated versions of AUDIT are similar in South Korea to other countries.
Adult ; Alcohol-Related Disorders ; Alcoholism ; Drinking ; Humans ; Korea ; Nutrition Surveys* ; ROC Curve ; World Health Organization

A clinical & statistical analysis was made on 325 cases of premature & low birth weight infants, admitted to the department of Pediatrics, National Medical Center, during the period. Of September, 1968 to august, 1976. The results obtained were as follows. 1. Sex ratio was 1.1 :1 between male & female. 2. Monthly distribution showed higher incidence in cold season than in warm season. 3. In regard to the place of delivery, there showed increasing tendency of hospital delivery. 4. Important predisposing factors disclosed toxemia of pregnancy, inappropriate pelvic condition, acute infection & twin delivery in order of frequency. Among them toxemia of pregnancy was the most important. 5. Overall incidence of premature delivery was 5.0% in 1968 and 3.1% in 1975 and revealed. Decreasing tendency. 6. Concerning the order of pregnancy, the highest incidence was among the 1st pregnancy. (33.2%). 7. In low birth weight infants, Apgar score was higher weight group. 8. The mortality rate was higher in males and in the group of out side delivery. The highest mortality rate was noted in the birth weight group of 1001-1250 gm. The larger the gestational period the lower the mortality rate was also noted. 9. Most of the deaths occurred during the first 48 hours and sharp decrease after the 3rd day of life. Main causes of death were idiopathic respiratory distress syndrome and pneumonia. 10. Initial weight loss was marked between the 7 th and 11 th day of life and about 10% of birth weight. The lower weight group showed the greater loss. 11. Regain as well as true weight gain during the 1 st month of life was slower in low birth weight group.
Apgar Score ; Birth Weight ; Causality ; Cause of Death ; Female ; Humans ; Incidence ; Infant* ; Infant, Low Birth Weight* ; Infant, Newborn ; Male ; Mortality ; Pediatrics ; Pneumonia ; Pre-Eclampsia ; Pregnancy ; Seasons ; Sex Ratio ; Weight Gain ; Weight Loss

Patient survival is one of the most important measures for the evaluation of progress in cancer patient care across the wide spectrum from diagnosis to treatment. The optimal monitoring method for cancer patient survival is to estimate survival based on representative data from cancer patients in the population, which is only achievable through using population-based cancer registration data. Relative survival is used to compare the survival experience in a study cohort that expected to result from background population mortality rates. This technique is useful when the cause of death is not accurate or not available, since it provides a measure of excess mortality in a group of patients with a certain disease. The purpose of this article is to demonstrate the procedures for estimating relative survival using the statistical software Stata. For this survival analysis to show the procedure, the example data set was randomly selected from the National Cancer Incidence Database, which was used in a recent article reporting the overall relative survival of cancer patients diagnosed during 1993-2002 in Korea.
Cause of Death ; Cohort Studies ; Dataset ; Diagnosis ; Humans ; Incidence ; Korea ; Mortality ; Patient Care ; Survival Analysis*

BACKGROUND: The cyclin D1 gene is one of the most frequently amplified chromosomal regions(11ql3) in human carcinomas. In laryngeal and head and neck carcinomas, its overexpression has been shown to be associated with advanced local invasion and presence of lymph node metastases. Cyclin D1 may therefore play a key role in cell growth regulation and tumorigenesis. Lung cancer is a worldwide problem and in many contries it is the most lethal malignancy. As relapse is frequent after resection of early stage non-small cell lung cancer, there is an urgent need to define prognostic factors. PURPOSE: This study was undertaken to evaluate the prognostic value of the cyclin D1, that is one the G1 cyclins which control cell cycle progression by allowing G1 to S phase transition, on the patients in radically resected non-small cell lung cancer. METHOD: Total Si cases of formalin-fixed paraffin-embedded blocks from resected primary non-small cell 11mg cancer from January 1., 1983 to July 31, 1995 at Hanyang University Hospital were available for both clinical follow-up and immunohistochemical staining using monoclonal antibodies for cyclin D1. RESULTS: The histologic classification of the tumor was based on WHO criteria, and the specimens included 45 squamous cell carcinomas, 25 adenocarcinomas and 11 large cell carcinomas. Cyclin D1 overexpression was noted in 26 cases of 81 cases tested (30.9%). Cyclin D1 expression was not significantly associated with cell types of the tumor, pathological staging and the size of the tumor. But cyclin D1 overexpression was significantly correlated with positive lymph node metastasis(p=0.035). The mean survival duration was 22.76+/-3.50 months in cyclin D1 positive group and 45.38 +/- 5.64 months in cyclin D1 negative group. There was a nearly significant difference in overall survival Between cyclin D1 positive and negative groups(p=0.0515) in radically resected non-small cell lung cancer. CONCLUISON: Based on this study, cyclin D1 overexpressiom appears at important poor prognostic indicator in non-small cell lung cancer and may have diagnostic and prognostic importance in the treatment of resectable non-small cell lung cancer.
Adenocarcinoma ; Antibodies, Monoclonal ; Carcinogenesis ; Carcinoma, Large Cell ; Carcinoma, Non-Small-Cell Lung* ; Carcinoma, Squamous Cell ; Cell Cycle ; Classification ; Cyclin D1* ; Cyclins* ; Follow-Up Studies ; Genes, bcl-1 ; Head ; Humans ; Lung Neoplasms ; Lymph Nodes ; Neck ; Neoplasm Metastasis ; Recurrence ; S Phase

Miller-Dieker syndrome is a multiple malformation syndrome characterized by severe lissencephaly and characteristic facial abnormalities at birth. It is associated with visible or submicroscopic deletions within chromosome 17p13.3 including PAFAH1B1 (LIS1) gene. We report a six-month-old boy who presented with spasm and generalized myoclonic seizures. The patient was born at 40 weeks' gestation to a 36-year-old woman and showed developmental delay without microcephaly or prominent facial abnormality. Magnetic resonance imaging of the brain showed a few gyrus (lissencephaly). High resolution cytogenetic analysis from peripheral blood showed a normal karyotype. However, fluorescence in situ hybridization (FISH) of the metaphase chromosome using Miller-Dieker/ILS probe (Oncor, Gaithersburg, Maryland, USA) revealed only one signal of probe, indicating a microdeletion of 17pl3.3 region including PAFAH1B1 (LIS1) gene. We suggest that FISH 17p13.3 studies should be performed in addition to a standard metaphase analysis in patients with lissencephaly even if facial anomaly is not noted. A confirmatory diagnosis using FISH would be helpful in terms of leading to allow genetic counseling and availability prenatal diagnosis to the family.
Adult ; Brain ; Classical Lissencephalies and Subcortical Band Heterotopias* ; Cytogenetic Analysis ; Diagnosis ; Female ; Fluorescence ; Genetic Counseling ; Humans ; In Situ Hybridization ; Karyotype ; Lissencephaly ; Magnetic Resonance Imaging ; Male ; Maryland ; Metaphase ; Microcephaly ; Parturition ; Pregnancy ; Prenatal Diagnosis ; Seizures ; Spasm

BACKGROUND: Donor granulocyte transfusion has been used as a salvage treatment for neutropenic patients with severe infection who did not respond to antibiotics. Here we investigated hematological parameters of granulocyte collection to evaluate its efficacy and safety. METHODS: The clinical data for 92 procedures of granulocyte collection performed on 82 healthy donors from April 2007 to July 2014 at National Cancer Center were reviewed retrospectively. Healthy donors were pre-medicated 12 hours before apheresis with subcutaneous injection of 600 microg of granulocyte-colony stimulating factor (G-CSF) with or without 8 mg of oral dexamethasone. Blood cell counts of donors at the time of pre- and post- granulocyte collection state of donors were investigated and any clinical symptoms and signs were monitored during the procedure. RESULTS: he median age was 29 years old (range, 18~52). The mean of collected granulocyte volume was 230 mL, and the granulocyte yield in apheresis products was 4.90x10(10) (1.46~7.86). Granulocyte yields showed significant correlation with volume of granulocyte collection, total processing volume, pre-WBC count, and pre-ANC. Granulocyte yields of dexamethasone and G-CSF administration were greater than with G-CSF administration alone. Pain (low back, hip, knee, and whole body), insomnia, fatigue, abdominal discomfort, and/or headache occurred in 21% of donors during mobilization. CONCLUSION: Granulocyte mobilization was safe and effective, and is well-tolerable in healthy donors because collection was possible in all donors without complications of G-CSF and dexamethasone administration and apheresis.
Anti-Bacterial Agents ; Blood Cell Count ; Blood Component Removal ; Dexamethasone ; Fatigue ; Granulocyte Colony-Stimulating Factor ; Granulocytes* ; Headache ; Hip ; Humans ; Injections, Subcutaneous ; Knee ; Retrospective Studies ; Sleep Initiation and Maintenance Disorders ; Tissue Donors*

BACKGROUND: Polycythemia vera (PV) is a myeloproliferative neoplasm that can cause complications such as thrombosis and organ damage. To prevent complications of PV, therapy for maintenance of a hematocrit target of less than 45% has been recommended and phlebotomy is a simple therapy. However, the effects of phlebotomy have not been well evaluated in Korea. Therefore, we evaluated the effects of phlebotomy performed in patients with PV and secondary polycythemia. METHODS: The clinical data and phlebotomy records of 15 patients diagnosed with PV and secondary polycythemia from May 2005 to March 2013 at the National Cancer Center were reviewed retrospectively. RESULTS: Patients included 10 males and five females. The median age of patients was 63 years (range, 50~72 years). There were six PV patients (40%) and nine secondary polycythemia patients (60%). The mean number of phlebotomy attempts per patient was 6 (range, 1~22), with an interval between phlebotomy attempts of 16 weeks (range, 1~96 weeks). The mean phlebotomy volume was 458 mL, which was 10.3% of the total blood volume. After phlebotomy, the mean hematocrit showed a decline, from 50.4 (+/-4.35)% to 46.5 (+/-4.85)%, and symptoms improved. After phlebotomies, 10 patients achieved a hematocrit of less than 45% and this hematocrit level was obtained after an average of six phlebotomies. CONCLUSION: Phlebotomy is an effective treatment modality for lowering the hematocrit value in patients with PV and secondary polycythemia. However, target hematocrit was not achieved after a single phlebotomy. Therefore, adjustment of visit intervals and changes in phlebotomy volume were needed.
Blood Volume ; Female ; Hematocrit ; Humans ; Korea ; Male ; Phlebotomy* ; Polycythemia Vera* ; Polycythemia* ; Retrospective Studies ; Thrombosis

BACKGROUND: Therapeutic leukapheresis is the cytoreduction procedure performed before chemotherapy in patients with hyperleukocytosis for prevention of complication. However, there have been clinical concerns about bleeding tendency due to anticoagulant used during the procedure. The aim of our study was to compare the clinical characteristics and hematological parameters before and after therapeutic leukapheresis in order to evaluate its effect on bleeding tendency and to provide a guideline for treatment strategy. METHODS: The clinical data for 39 procedures of therapeutic leukapheresis performed on 17 patients with hyperleukocytosis from May 2005 to October 2013 at the National Cancer Center were reviewed retrospectively. RESULTS: The patients consisted of 11 males and six females. The mean age was 41 years old (range, 8~74). The mean number of therapeutic leukapheresis per patient was two (range, 1~4). Clinical symptoms improved in 14 patients (82%) after therapeutic leukapheresis and three patients (18%) were not yet to improve. The mean WBC count was significantly reduced by 32.6% (+/-17.4) after therapeutic leukapheresis, from 250,146/microL (+/-117,000) to 174,702/microL (+/-104,700) (P<0.001). The mean volume of single removal was 298 ml with 4.25x10(11)/L (+/-1.54) WBCs. After therapeutic leukapheresis, the mean platelet count showed a decline from 85x10(9)/L (+/-43) to 71x10(9)/L (+/-26). However, the prothrombin time (PT) and activated partial thromboplastin time (aPTT) did not show a significant increase (PT, P=0.637; aPTT, P=0.054). CONCLUSION: Therapeutic leukapheresis is demonstrated as an effective and safe treatment that can improve symptoms and reduce leukocytes in hyperleukocytosis.
Drug Therapy ; Female ; Hemorrhage ; Humans ; Leukapheresis* ; Leukocytes ; Leukostasis ; Male ; Partial Thromboplastin Time ; Platelet Count ; Prothrombin Time ; Retrospective Studies