MSK1 regulates RANKL-induced NFATc1 expression through CREB and c-Fos / 동물의과학연구지

Osteoclasts originated from hematopoietic stem cells are multi-nucleated cells that can resorb the bone matrix. Receptor activator of nuclear factor kappa-B (RANK)/RANK ligand (RANKL) signaling pathway is crucial for the differentiation and activation of osteoclasts. In this study, we investigated for the first time whether or not RANKL induced mitogen- and stress-activated kinase 1 (MSK1) phosphorylation at Ser 376. Activation of MSK1 was detected as soon as 5 min after RANKL stimulation and sparsely detected at 30 min after stimulation. RANKL-induced MSK1 phosphorylation occurred in a dose-dependent manner. MSK1 is known as a downstream signaling molecule of cAMP-dependent protein kinase (PKA). Treatment with the PKA inhibitor H89 significantly suppressed c-Fos and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) induction upon RANKL stimulation. In addition, cAMP response element-binding protein (CREB) phosphorylation was extremely inhibited by H89 treatment. Mitogen-activated protein kinases (MAPKs) have been investigated for induction of MSK1 phosphorylation. Specific signaling pathway inhibitors for p38 and extracellular signal-regulated kinases (ERKs) significantly blocked RANKL-induced MSK1 activation. Finally, as a downstream effector of the p38-MSK1 pathway, c-Fos transcriptional activity was determined. RANKL-mediated elevation of c-Fos transcriptional activity was significantly suppressed by p38 inhibitor. Moreover, a dominant negative form of CREB suppressed activation of NFATc1. In conclusion, RANKL-stimulated MSK1 phosphorylation could play a role in induction of NFATc1 through CREB and c-Fos activation as a downstream molecule of p38, ERK MAPKs, and PKA. Our results support basic information for the development of osteoclast specific inhibitors.

Coxsackievirus B Infection Is Highly Related with Missed Abortion in Korea

PURPOSE: This study investigated the possible relationship between viral infection and first trimester pregnancy loss. MATERIALS AND METHODS: A prospective study was performed on 51 gravidas with missed abortion, fetal anomaly, pre-term delivery, and full-tem delivery at Hanyang University Hospital. Enteroviruses were detected by semi-nested reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry in abortive tissues and placentas. Enterovirus serotypes were confirmed by genome sequencing. Herpesviruses were detected by PCR. RESULTS: Coxsackievirus B3 (CVB3) was detected in 8 of 14 missed abortion cases, 1 of 27 full-term cases, and none of the 9 pre-term cases. Coxsackievirus B1 (CVB1) was detected in an encephalocele case. Herpes simplex virus type 1 was found in 4 full-term cases, 3 pre-term cases, and none of the missed abortion cases. CONCLUSION: The prevalence of CVB3 was significantly higher in missed abortion cases compared to full-term or pre-term delivery cases. CVB infection may therefore be an important etiological agent of missed abortion.

Current status of assisted reproductive technology in Korea, 2009

Great advances have been made in the field of assisted reproductive technology (ART) since the first in vitro fertilization (IVF) baby was born in Korea in the year of 1985. However, it deserve to say that the invaluable data from fertility centers may serve as a useful source to find out which factors affect successful IVF outcome and to offer applicable information to infertile patients and fertility clinics. This article intended to report the status of ART in 2009 Korean Society of Obstetrics and Gynecology surveyed. The current survey was performed to assess the status and success rate of ART performed in Korea, between January 1 and December 31, 2009. Reporting forms had been sent out to IVF centers via e-mail, and collected by e-mail as well in 2012. With International Committee Monitoring Assisted Reproductive Technologies recommendation, intracytoplasmic sperm injection (ICSI) and non-ICSI cases have been categorized and also IVF-ET cases involving frozen embryo replacement have been surveyed separately. Seventy-four centers have reported the treatment cycles initiated in the year of 2009, and had performed a total of 27,947 cycles of ART treatments. Among a total of 27,947 treatment cycles, IVF and ICSI cases added up to 22,049 (78.9%), with 45.3% IVF without ICSI and 54.7% IVF with ICSI, respectively. Among the IVF and ICSI patients, patients confirmed to have achieved clinical pregnancy was 28.8% per cycle with oocyte retrieval, and 30.9% per cycle with embryo transfer. The most common number of embryos transferred in 2009 is three embryos (40.4%), followed by 2 embryos (28.4%) and a single embryo transferred (13.6%). Among IVF and ICSI cycles that resulted in multiple live births, twin pregnancy rate was 45.3% and triple pregnancy rate was 1.1%. A total of 191 cases of oocyte donation had been performed to result in 25.0% of live birth rate. Meanwhile, a total of 5,619 cases of frozen embryo replacement had been performed with 33.7% of clinical pregnancy rate per cycle with embryo transfer. When comparing with international registry data, clinical pregnancy rate per transfer from fresh IVF cycles including ICSI (34.1%,) was comparable to clinical pregnancy rate per transfer in European Society for Human Reproduction and Embryology report was 32.5% though lower than 45.0% for USA data. There was no remarkable difference in status of assisted reproductive technology in Korea between the current report and the data reported in 2008. The age of women trying to get pregnant was reconfirmed to be the most important factor that may have impact on success of ART treatment.

Adherence to Varenicline and Abstinence Rates for Quitting Smoking in a Private Health Promotion Center-Based Smoking Cessation Clinic / 결핵및호흡기질환

BACKGROUND: Varenicline is an effective smoking cessation aid. However, smokers prescribed with varenicline do not always receive varenicline for 12 weeks, as recommended. This study analyzed the subjects who received varenicline and investigated the effect of varenicline treatment duration on the success rate of 6-month smoking cessation. METHODS: This study retrospectively analyzed 78 subjects, who received varenicline, out of the 105 smokers that had visited the smoking cessation clinic after medical examination from September 2007 to December 2009. RESULTS: The subjects were all males. Twenty-two subjects (28.2%) had varenicline treatment for 12 weeks or longer; 18 subjects (23.1%) for 8~12 weeks; 22 subjects (28.2%) for 4~8 weeks; and 16 subjects (20.5%) for less than 4 weeks. The total success rate of the 6-month smoking cessation was 47.4%. The success rate of the 6-month smoking cessation was 63.6% in the group that received varenicline for 12 weeks or longer, which was higher than 41.1% of the group that early terminated the varenicline treatment (p=0.074). The period of varenicline treatment was extended for one more week, the odds ratio of the 6-month smoking cessation success increased to 1.172-folds (p=0.004; 95% confidence interval, 1.052~1.305). Adverse events occurred in 30.8% of the subjects who received varenicline, but no serious adverse events were found. CONCLUSION: If varenicline treatment period is extended, the odds ratio of the success rate for the 6-month smoking cessation increases. Therefore, an effort to improve drug compliance for varenicline in clinical practices could be helpful for the long-term success of smoking cessation.

Difference of the Results of Two Visits in Down Syndrome Screening Test / 임상검사와정도관리

INTRODUCTION: Estimation of the risk of Down syndrome pregnancy by the triple marker test is performed on women once at anytime during the 15-21 weeks of gestational age. The triple marker test is based on the distribution of the alpha-fetoprotein (AFP), chorionic gonadotropin (CG) and unconjugated estriol (uE3) of the different pregnancy. In spite of the logical excellencies, various factors can affect the result of the test in practical field. We compared differences of the risk of Down syndrome pregnancy based on the specimen obtained from two visits during the 15-21 weeks of gestational age. METHOD: We measured the AFP, CG and uE3 with Access (Beckman Coulter, USA) from the sera of 104 pregnant women who visited two times about 2 weeks of interval during 15-21 weeks of gestational age. We calculated log (MoM) of AFP, CG and uE3 of each marker between two visits, and compared differences of each biochemical marker and difference of risk of Down syndrome pregnancy between two visits. RESULT: Mean+/-SD of log (MoM) of AFP, CG, uE3 of the 1st visit were 0.019+/-0.156, -0.016+/-0.224, 0.002+/-0.138, respectively, and those of AFP, CG, uE3 of the 2nd visit were 0.010+/-0.140, -0.076+/-0.205, 0.057+/-0.138, respectively. CG and uE3 showed statistically significant difference (P<0.001, P<0.001, respectively) but AFP did not (P=0.328). Risk of Down syndrome pregnancy of the 1st visit was 8.017x10(-4)+/-1.6241x10(-3), and that of the 2nd visit was 5.667x10(-4)+/-1.6241x10(-3), with no significant difference statistically (P=0.094). CONCLUSION: The risk of Down syndrome based on the sera of woman who visited two times about 2 weeks of interval between 15-21 weeks of gestational age did not show significant difference. It is resonable that triple marker test is performed on women once at anytime during the 15-21 weeks of gestational age in practical base.

A comparison of criteria of gestational diabetes using 100 gm oral glucose tolerance test in Korean women / 대한산부인과학회지

OBJECTIVE: The purpose of this study was to compare the National Diabetes Data Group (NDDG) with the American Diabetes Association (ADA) criteria proposed by Carpenter and Coustan for determining gestational diabetes using the 100 gm oral glucose tolerance test (GTT) in Korean women. METHODS: Seventeen-hundred pregnant women who underwent a 50 g oral GTT and delivered in the department of Ob/Gyn, Hanyang Univ Guri Hospital, between March, 1999 and February, 2004 were the subjects of this study. The women were categorized into A through D groups as follows: euglycemic control subjects (A), subjects with non gestational diabetes diagnosed by the NDDG and ADA criteria (B), subjects with gestational diabetes diagnosed by only the ADA criteria but not the NDDG criteria (C) and subjects with gestational diabetes diagnosed by only the NDDG criteria (D). The general characteristic and pregnancy outcomes were compared for each groups. The effectiveness of the ADA criteria was determinined by macrosomia and preeclampsia after controlling for confounding risk factors by logistic regression modeling. RESULTS: Of the 1700 pregnant women, 1420 women were classified in group A, 184 women were in group B, 28 women were in group C and 68 women were in group D. The group D showed more obese and less gestational weeks at delivery than the other groups. In pregnancy outcomes, groups B, C, and D showed more weighted average birth weight and higher frequency of macrosomia of the fetus than in group A. No differences existed among the 4 groups regarding intrauterine growth restriction, preeclampsia, and cesarean section. The risk factors of macrosomia were groups B, C, and D that shows glucose intolerance, obesity and more higher weight gain during pregnancy. Even after controlling for confounding risk factors by logistic regression modeling, groups B, C, and D were risk factors for macrosomia. Especially, the odds ratio for group C has shown a higher risk factor at 7.6 as compared to group D at 5.3. Glucose intolerance was not shown to be a risk factor of preeclampsia. CONCLUSION: Because glucose intolerance as shown in abnormal 50 g oral GTT is a risk factor for macrosomia and more weighted average birth weight of the fetus in Korean women, the diagnostic standards for Korean women are more suited to the ADA criteria compared to the NDDG criteria.

Current Concepts of Stem Cell Therapy / 대한산부인과학회지

Stem cells are defined by their capacity for self-renewal and multilineage differentiation, making them uniquely situated to treat a broad spectrum of human diseases. The transplantation of tissue-specific stem cells, such as stem cells isolated from epithelial and neural tissues, can treat mouse disease models and human patients in which epithelial and neural cells are damaged. An alternative to tissue-specific stem cell therapy takes advantage of embryonic stem cells, which are capable of differentiating into any tissue type. Furthermore, nuclear transfer, the transfer of a post-mitotic somatic cell nucleus into an enucleated oocyte, creates a limitless source of autologous cells that, when combined with gene therapy, can serve as a powerful therapeutic tool.

Partial Interferon-gamma Receptor Deficiency in Patients with Disseminated Tuberculosis / 결핵및호흡기질환

BACKGROUND: Interferon-gamma (IFN-gamma) is essential in the immune response to mycobacterial infections, and a complete or partial deficiency in the IFN-gamma receptor 1 (IFNgammaR1) or the IFN-gamma receptor 2 (IFNgammaR2) have been reported to confer susceptibility to a disseminated infection with nontuberculous mycobacteria. However, similar mutations in the IFN-gamma receptor have not been specifically examined in the patients with clinical tuberculosis. METHODS: This study searched for mutations in the IFN-gamma receptor gene that resulted in a partial IFN-gamma receptor deficiency in six patients with disseminated tuberculosis. The previously identified IFNgammaR1 and IFNgammaR2 coding regions were sequenced after amplification. RESULTS: There was no partial IFNgammaR1 deficiency including a homozygous recessive missense mutation causing an amino-acid substitution in the extracellular domain of the receptor (I87T) and a hotspot for small deletions (818delT, 818del4, 818insA) found in any of the patients. In addition, a partial IFNgammaR2 deficiency of the homozygous missense mutation (R114C) was not found in any of the patients. CONCLUSION: Genetic defects causing a partial IFN-gamma receptor deficiency were not identified in our patients with disseminated tuberculosis.

The effects of BMP4 and BMP2 on Expression of Trophoblast-Specific Genes in Human Embryonic Stem Cells using SNU-hES3 cell line / 대한산부인과학회지

OBJECTIVE: Human embryonic stem cell derived from blastocyst randomly differentiates into multiple cell types during embryoid body development. Bone morphogenetic proteins (BMPs) are members of the transforming growth factor type beta superfamily. We have a question whether BMP2 and/or BMP4 can induce trophoblast specific genes in human ES cells using SNU hES3 cell line. METHODS: Human embryonic stem cell line (SNU hES3) was supplied by Miz Medi Hospital Seoul National University. Cultured hES cells were divided into small clumps and then allow for EB formation in differentiation medium. After EB formation, EBs were transferred onto gelatin coated dishes and given hES conditioned medium alone (control) or supplemented as following treatment for 6 days; rhBMP4 100 ng/mL; rhBMP2 100 ng/mL; BMP4 100 ng/mL +BMP2 100 ng/mL. RT PCR was performed for trophoblast specific genes. During culture, supernatant was collected and measured for estradiol (E2), progesterone, and hCG beta by enzymeimmuno assay (EIA) kit. RESULTS: BMP4 and BMP2 increase chorionic gonadotropin beta (hCG beta), glical cell missing 1 (GMC1), and CD9 as trophoblast specific gene markers confirmed by RT PCR. However, the non classical HLA class I molecule HLAG1, was not expressed in our studies. And we cannot find significant differences of the level of estradiol, hCG nd progesterone in this study. CONCLUSION: The results suggest that BMP 4 and 2 have an additive effect on induction of trophoblast related genes in SNU hES3 cell line. Although we failed to induce the differentiation of human ES cells to trophoblast, this study could provide the possibility for the differentiation of early human trophoblast cells and thus need further studies.

Treatment of Isoniazid-Resistant Pulmonary Tuberculosis / 결핵

BACKGROUND: As an effective regimen for isoniazid (INH)-resistant pulmonary tuberculosis, several treatment regimens have been recommended by many experts. In Korea, a standard regimen has not been established for INH-resistant tuberculosis, and the treatment by individual physicians has been performed on an empirical bases. The purpose of the present study was to retrospectively describe the treatment characteristics and evaluate the treatment outcomes of patients with INH-resistant tuberculosis. MATERIALS AND METHODS: Sixty of 69 patients reported to have INH-resistant tuberculosis from 1994 to 2001 were retrospectively analyzed. Exclusion criteria included: death from other causes, with the exceptions of tuberculosis and incomplete treatment, including a patient's transfer-out. RESULTS: A previous tuberculosis history was found in 28 (46.7%) patients. The sputum smear for acid-fast bacilli was positive in 44 (73.3%) patients, and 30 (50.0%) had cavitary disease. Streptomycin resistance coexisted in 25.0% of isolates. INH was to be prescribed continuously, even after INH resistance was reported, in 86.0% of patients. The treatment regimens were diverse between the patients according to drug regimen composition and treatment duration. The most frequent prescribed regimen included rifampin, ethambutol and pyrazinamide, with and without INH, for the full 12-month term of treatment. Treatment failure occurred in 13 (21.7%) patients. Cavitary disease (p=0.005) and a treatment regimen with second-line drugs, excluding rifampin (p=0.015), were associated with treatment failure. One patient experienced a relapse. CONCLUSIONS: Standardized treatment guidelines will be needed in Korea to improve the treatment efficacy for INH-resistant tuberculosis.

Usefulness of Tuberculin Test in Adult Patients with Suspected Pulmonary Tuberculosis / 결핵

BACKGROUND: The tuberculin skin test has been used to diagnose latent tuberculosis infection, but is not widely used to diagnose or exclude pulmonary tuberculosis. The objective of this study was to evaluate the diagnostic utility of the tuberculin test in diagnosing and excluding pulmonary tuberculosis, and differentiating pulmonary tuberculosis from nontuberculous mycobacteria (NTM) pulmonary disease, when a sputum acid-fast bacilli (AFB) smear was positive. MATERIAL AND METHODS: From October 2002 to August 2003, among all the inpatients of the Division of Pulmonary and Critical Care Medicine at Samsung Medical Center, 258 patients with clinical suspicion of pulmonary tuberculosis were enrolled and underwent a tuberculin test. RESULTS: 156 males and 102 females were included, with a mean age of 57.5 years. The final diagnoses included lung cancer in 89 cases (34.5%), pulmonary tuberculosis in 59 cases (22.9%), bacterial pneumonia in 33 cases (12.8%) and NTM pulmonary disease in 24 cases (9.3%). The positive tuberculin test rate was higher in the tuberculosis than non-tuberculosis group; 81.4 (48/59) vs. 42.4% (81/199). (p<0.001). In 208 patients with a negative sputum AFB smear, the result of the tuberculin test was positive in 69.4% (25/36) of the tuberculosis group and in 44.8% (77/172) of the non-tuberculosis group (p=0.007), so a positive result of the tuberculin test could predict pulmonary tuberculosis with 69.4% sensitivity, 55.2% specificity, a 24.5% positive predictive value and a 89.6% negative predictive value. In 50 patients with a positive sputum AFB smear, the positive rates of the tuberculin test were 83.9% (26/31) in tuberculosis group and 21.1% (4/19) in NTM pulmonary disease group (p<0.001), so a positive result of the tuberculin skin test could predict pulmonary tuberculosis with 83.9% sensitivity, 78.9% specificity, a 86.7% positive predictive value and a 75.0% negative predictive value. CONCLUSION: The tuberculin test could be useful in excluding pulmonary tuberculosis when the sputum AFB smear is negative, and to differentiate pulmonary tuberculosis from NTM pulmonary disease when the sputum AFB smear is positive.

A Case of Thyrotoxic Storm Triggered by Virgorous Palpation of Thyroid Gland After Delivery / 대한산부인과학회잡지

Although the mortality has been reduced with aggressive approach, thyrotoxic storm or crisis is still a life-threatening condition and usually triggered by preeclampsia, placenta previa, congestive heart failure, infections and induction of labor during pregnancy. We report here a 28-year-old pregnant woman suspicious of placenta previa without a previous history of hyperthyroidism was admitted to the hospital with vaginal spotting and labor. After receiving a Cesarean section, thyrotoxic manifestations were developed and she became stable with antithyroid therapy. The second attack of thyrotoxic storm was presented after a thyroid ultrasonographic study. It appears that the vigorous examination of thyroid gland carries a significant risk of thyrotoxic crisis in poorly controlled hyperthyroidism.

Expressions of Leukemia Inhibitory Factor (LIF): Comparison of Normal Pregnancy and Recurrent Abortion / 대한산부인과학회잡지

OBJECTIVE: Successful implantation depends on a complex interaction between the developing blastocyst and the endometrium. Among the steroid hormones, growth factors, and cytokines which participate in preparing the uterus for implantation, leukemia inhibitory factor (LIF) plays an essential role in implantation. We compared the expression of LIF in normal pregnancies to that of recurrent abortions in placenta to elucidate whether spontaneous abortion and expression of LIF has correlation. METHODS: Placental tissues from normal pregnancies and recurrent abortions were fixed and embedded in paraffin. Standard immunohistochemical staining was used to identify LIF. RESULTS: LIF expressions on cytotrophoblast of recurrent abortion were lower than those of normal pregnancy. There were no expressions on syncytiotrophoblast and stroma in the both groups. In the decidua and gland, LIF was expressed in mild degree and there were no differences in LIF expression between normal pregnancy and recurrent abortion. CONCLUSION: LIF expression on cytotrophoblast of recurrent abortion was lower than that of normal pregnancy. LIF may provide paracrine and autocrine signals to both embryonic tissues and uterine epithelium during implantation. The dysfunction of LIF production may be a cause of the unexplained recurrent abortions.

The Effect of Leukemia Inhibitory Factor in Decidualizing Human Endometrial Stromal Cells / 대한산부인과학회잡지

OBJECTIVE: Decidualization of endometrial stromal cells is essential for a successful implantation of the embryo. The process of decidualization can be modulated by sex steroids, growth factors and cytokines. Leukemia inhibitory factor (LIF) is a pleiotropic cytokine of the interleukin-6 family and has different biological actions in various tissue systems. Recently, LIF has been reported as an important factor for adequate decidualization of endometrium. However, the effect on production of prolactin (PRL), known as the decidualization marker, are not clearly understood. The objective of this study was to determine whether LIF is capable of modulating prolactin production during 8-bromo (Br)-cAMP induced decidualization in vitro. METHODS: Human endometrial stromal cells were cultured and decidualization was induced by 0.5 mM 8-Br-cAMP. Phase contrast microscopy was used to verify morphological changes associated with differentiation in vitro in response to 8-Br-cAMP. Both stromal cells exposed to 8-Br-cAMP and cells not exposed to 8-Br-cAMP were also incubated with LIF (10 ng/mL). PRL levels in each supernatant were measured by a commercial PRL ELISA kit. Immunostaining and reverse transcription-polymerase chain reaction (RT-PCR) for PRL were performed. RESULTS: The concentration of PRL in the supernatant increased significantly in the cells treated with 8-Br-cAMP plus LIF (10 ng/mL) at culture day 6 compared with the others. The results of immunohistochemical staining reflected that of immunoassay. The PRL genes are expressed in the decidualized stromal cells treated with 8-Br-cAMP. No PRL mRNA was detectable in the absence of the 8-Br-cAMP. The intensity of the PCR band measured by densitometry is stronger in the cells treated with 8-Br-cAMP plus LIF than that with the others. CONCLUSION: These results suggested that LIF increased the production of PRL in decidualizing human endometrial stromal cells and may play a role in preparing the human endometrium for implantation through the promotion of PRL production.

Prone Positioning Improves Oxygenation Without Adverse Hemodynamic Effects during Partial Liquid Ventilation in a Canine Model of Acute Lung Injury

BACKGROUND: Partial liquid ventilation (PLV) and prone positioning can improve the arterial oxygenation (PaO2) in acute lung injury (ALI). We evaluated the effect of prolonged prone positioning during partial liquid ventilation (PLV) in a canine model of acute lung injury. METHODS: Six mongrel dogs (weighing 17.4 +/- 0.7 kg each) were anesthetized, intubated and mechanically ventilated. After 1 hour of baseline stabilization, the dogs' lungs were instilled with 40 mL/kg perfluorocarbon (PFC). PLV was first performed in the supine position for 1 hour (S1), then in the prone position for 3 hours with hourly measurements (P1, P2, P3), and finally, PLV was performed with the animal turned back to the supine position for 1 hour (S2). RESULTS: After instillation of the PFC, the PaO2 significantly increased from 99.2 +/- 32.6 mmHg at baseline to 198.1 +/- 59.2 mmHg at S1 (p=0.001). When the dogs were turned to the prone position, the PaO2 further increased to 288.3 +/- 80.9 mmHg at P1 (p=0.008 vs. S1) : this increase was maintained for 3 hours, but the PaO2 decreased to 129.4 +/- 62.5 mmHg at S2 (p< 0.001 vs. P3). Similar changes were seen in the shunt fraction. There were no significant differences for the systemic hemodynamic parameters between the prone and supine positions. CONCLUSION: Prolonged prone positioning during PLV in an animal model of ALI appears to improve oxygenation without any hemodynamic compromise.

Short-term Clinical Experience on Interferon gamma-1b Therapy for Idiopathic Pulmonary Fibrosis / 결핵

BACKGROUND: Corticosteroids in combination with cytotoxic drugs are the mainstays of therapy for idiopathic pulmonary fibrosis (IPF). However, there has been no regimen showing any survival benefit. The aim of this study was to describe a short-term clinical experience on interferon gamma-1b (IFN-gamma1b) therapy for IPF, as an antifibrotic agent. METHODS: Medical records of 27 patients who were treated with IFN-gamma1b (2 million IU, 3 times a week, subcutaneous injection) were retrospectively reviewed. Treatment response was assessed using ATS/ERS criteria in 17 patients who received IFN-gamma1b for more than 6 months. In addition, we compared the efficacy of IFN-gamma1b therapy with that of cyclophosphamide+/-prednisolone therapy (n=26). RESULTS: The median age of IFN-gamma treated group (M:F=19:8) was 59 years (44-74 years). Compared to the patients who showed a stable response at 6 months (n=12), the deteriorated group (n=5) had worse baseline lung function (FVC, 55.4+/-11.3% vs. 70.7+/-10.9%, p=0.019; DLco, 50.3+/-7.3% vs. 76.9+/-19.6%, p=0.014). Lower baseline PaO2 on room air breathing was observed in the deteriorated group (68.6+/-7.8mmHg vs. 91.4+/-6.6mmHg p=0.001). Subcutaneous IFN-gamma1b did not show better efficacy than prednisolone. Five patients discontinued IFN-gamma because of severe side effects. ARDS developed in one patient, who eventually died. CONCLUSION: The administration of IFN-gamma1b is not desirable for patients diagnosed with IPF with poor lung function. Long-term and large-scaled clinical studies are needed for its efficacy in IPF.

Clinical Characteristics and Treatment Outcomes of Patients with Pulmonary Tuberculosis at a Private General Hospital / 결핵

BACKGROUND: Until the early 1990's in Korea, treatment outcomes of patients with pulmonary tuberculosis in the private sector were reported to be inferior to those of the public health center under the National Tuberculosis Programme. The purpose of this study was to analyze the clinical characteristics and the treatment efficacy of the patients with pulmonary tuberculosis recently diagnosed at a private general hospital. MATERIALS and METHODS: The study included all pulmonary tuberculosis patients diagnosed at Samsung Medical Center and notified to the public health center from August 2000 to January 2001. RESULTS: Of the 232 patients included in the study during a 6-month period, 188 were (81.0%) initial treatment cases and 44 (19.0%) were re-treatment cases. Eighty-three (35.8%) patients had smear-positive sputa, and 27 (11.6%) had smear-negative, culture-positive sputa. Initial sputum examinations were not performed in 47 (20.3%) patients. A six-month, short-course treatment using isoniazid, rifampin, ethambutol and pyrazinamide was prescribed for 31.4% of the patients under the initial treatment. The success rate (cured plus treatment completed) of the initial treatment for the smear-positive patients was 69.1%. Eleven (13.3%) of the 83 patients with smear-positive pulmonary tuberculosis discontinued their treatment without notice. CONCLUSIONS: To improve the treatment efficacy and decrease the default rates of the patients with pulmonary tuberculosis in the private sector, further efforts are required in line with the Korean Academy of Tuberculosis and Respiratory Disease Treatment Guidelines and in the implementation of an appropriate model of public-private mix for tuberculosis control in Korea.

Mediastinal Lymphangioma in Adults: Three Case Reports / 결핵

BACKGROUND: Lymphangioma of the mediastinum is an uncommon benign tumor of lymphatic origin that is most often seen in children, is very rare in adults and is frequently discovered incidentally on chest x-ray exams. While radiology (CT and MRI) may suggest the diagnosis and allow an assessment of the operative difficulties, the histology of the surgical specimen is required for precise diagnosis. Complete resection is the only treatment; however, in some patients resection was incomplete because of the infiltrating character of these tumors, leading to recurrence. We report three cases of mediastinal lymphangioma with a review of the literature.

X-linked Agammaglobulinemia Associated with Bronchiectasis: A Case Report / 결핵

Bronchiectasis is defined as an abnormal, irreversible dilatation of the bronchi, which may result from a number of possible causes, and the recognition of these causes may lead to a specific management strategy. Immunodeficiency is known as one of the conditions associated with bronchiectasis. X-linked agammaglobulinemia is a rare inheritable immunodeficiency disorder, caused by a differentiation block, leading almost to the complete absence of B lymphocytes and plasma cells. The affected protein is a cytoplasmic protein tyrosine kinase, Bruton's tyrosine kinase. The early detection and treatment with immunoglobulin replacement are most important for the management of recurrent infections and for reducing severe complications. We report a 20-year-old male patient, with X-linked agammaglobulinemia associated with bilateral bronchiectasis, carrying a missense mutation(R520P) in the BTK gene.

Comparison of Expression of Endometrial Prolactin in infertile Women with Luteal Phase Defect According to Clomiphene Citrate Administration / 대한불임학회지

OBJECTIVE Clomiphene citrate is one of the most commonly used drugs in the treatment of infertility, but the pregnancy rate achieved with clomiphene citrate is significantly lower than the ovulation rate due to its antiestrogenic effect on the endometrium. Endometrial prolactin is considered to be a marker and an inducer of predecidualization that is characteristic of secretory endometrium. The purpose of this study was to evaluate the association of clomiphene citrate and unsatisfactory endometrial differentiation to secretory endometrium by examining the endometrial expression of prolactin in clomiphene citrate-treated infertile women with luteal phase defect. METHODS: The endometrial samples from infertIle women wIth luteal phase defect (n=27) were examined. Five cases during secretory phase and six cases during proliferative phase were obtained by biopsy. Sixteen cases were obtained by biopsy during secretory phase after clomiphene citrate treatment. By immunohistochemical staining for prolactin, all obtained endometrial tissues were examined. The differences in the endometrial expression of prolactin were evaluated between proliferative phase and secretory phase, and between clomiphene citrate treated group and no treatment group during secretory phase. RESULTS: The staining of endometrial prolactin was significantly more intense in the glandular epithelial cells and stromal cells in the secretory endometrium than in the proliferative endometrium. The glandular expression of prolactin in the secretory endometrium was not significantly different between the clomiphene citrate-treated group and no treatment group (p=0.719), but the staining of prolactin in the stromal cells was significantly less intense in the clomiphene citrate-treated group than no treatment group (p=0.019). CONCLUSION: in this investigation, we demonstrated that the endometrial stromal expression of prolactin in the secretory phase was significantly lower in the clomiphene citrate-treated group campared with no treatment group in infertile women with luteal phase defect. And our finding suggests that clomiphene citrate may have an adverse effect on the endometrial predecidualization in infertile women.