Perceptual and Acoustic Outcomes of Early-Stage Glottic Cancer After Laser Surgery or Radiotherapy: A Meta-Analysis

Laser surgery (LS) or radiotherapy (RT) is normally recommended in early glottic cancer. The objective of this study was to perform a comprehensive meta-analysis of acoustic and perceptual outcomes to compare voice quality of LS or RT in early-stage glottic cancer. Data sources were obtained after searching PubMed, Google Scholar, EBSCO, and RISS using the following search terms: glottic cancer, glottic carcinoma, endoscopic surgery, laser surgery, radiotherapy, radiation, voice, voice quality, and grade, roughness, breathiness, asthenia, and strain (GRBAS) scale. Articles that compared voice outcomes between LS and RT were identified. This meta-analysis included 15 articles with 744 patients, including 400 in the LS group and 344 in the RT group. Random effects models were selected. Forest plots included standardized mean differences, standard errors, variance, 95% confidence intervals (lower limit to upper limit), z-values, and P-values. In perceptual analysis, grade (G) and asthenia (A) of RT were significantly better than LS. There was no statistically significant difference in roughness (R), breath (B), or strain (S) between LS and RT groups. Jitter, shimmer, and noise to harmonic ratio measurements showed significant differences, resulting in enhanced posttreatment effect of RT compared to LS. Results of our meta-analysis suggested that RT might lead to superior voice quality than LS in early glottic cancer.

Genetic Profiles Associated with Chemoresistance in Patient-Derived Xenograft Models of Ovarian Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Recurrence and chemoresistance (CR) are the leading causes of death in patients with high-grade serous carcinoma (HGSC) of the ovary. The aim of this study was to identify genetic changes associated with CR mechanisms using a patient-derived xenograft (PDX) mouse model and genetic sequencing. MATERIALS AND METHODS: To generate a CR HGSC PDX tumor, mice bearing subcutaneously implanted HGSC PDX tumors were treated with paclitaxel and carboplatin. We compared gene expression and mutations between chemosensitive (CS) and CR PDX tumors with whole exome and RNA sequencing and selected candidate genes. Correlations between candidate gene expression and clinicopathological variables were explored using the Cancer Genome Atlas (TCGA) database and the Human Protein Atlas (THPA). RESULTS: Three CR and four CS HGSC PDX tumor models were successfully established. RNA sequencing analysis of the PDX tumors revealed that 146 genes were significantly up-regulated and 54 genes down-regulated in the CR group compared with the CS group. Whole exome sequencing analysis showed 39 mutation sites were identified which only occurred in CR group. Differential expression of SAP25,HLA-DPA1, AKT3, and PIK3R5 genes and mutation of TMEM205 and POLR2A may have important functions in the progression of ovarian cancer chemoresistance. According to TCGA data analysis, patients with high HLA-DPA1 expression were more resistant to initial chemotherapy (p=0.030; odds ratio, 1.845). CONCLUSION: We successfully established CR ovarian cancer PDX mouse models. PDX-based genetic profiling study could be used to select some candidate genes that could be targeted to overcome chemoresistance of ovarian cancer.

Comparison of Clinical Features and Outcomes in Epithelial Ovarian Cancer according to Tumorigenicity in Patient-Derived Xenograft Models / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Although the use of xenograft models is increasing, few studies have compared the clinical features or outcomes of epithelial ovarian cancer (EOC) patients according to the tumorigenicity of engrafted specimens. The purpose of this study was to evaluate whether tumorigenicity was associated with the clinical features and outcomes of EOC patients. MATERIALS AND METHODS: Eighty-eight EOC patients who underwent primary or interval debulking surgery from June 2014 to December 2015 were included. Fresh tumor specimens were implanted subcutaneously on each flank of immunodeficient mice. Patient characteristics, progression-free survival (PFS), and germline mutation spectra were compared according to tumorigenicity. RESULTS: Xenografts were established successfully from 49 of 88 specimens. Tumorigenicity was associated with lymphovascular invasion and there was a propensity to engraft successfully with high-grade tumors. Tumors from patientswho underwent non-optimal (residual disease ≥ 1 cm) primary orinterval debulking surgery had a significantly greater propensity to achieve tumorigenicity than those who received optimal surgery. In addition, patients whose tumors became engrafted seemed to have a shorter PFS and more frequent germline mutations than patients whose tumors failed to engraft. Tumorigenicity was a significant factor for predicting PFS with advanced International Federation of Gynecology and Obstetrics stage and high-grade cancers. CONCLUSION: sTumorigenicity in a xenograft model was a strong prognostic factor and was associated with more aggressive tumors in EOC patients. Xenograft models can be useful as a preclinical tool to predict prognosis and could be applied to further pharmacologic and genomic studies on personalized treatments.

Generation of Insulin-Expressing Cells in Mouse Small Intestine by Pdx1, MafA, and BETA2/NeuroD

BACKGROUND: To develop surrogate insulin-producing cells for diabetes therapy, adult stem cells have been identified in various tissues and studied for their conversion into β-cells. Pancreatic progenitor cells are derived from the endodermal epithelium and formed in a manner similar to gut progenitor cells. Here, we generated insulin-producing cells from the intestinal epithelial cells that induced many of the specific pancreatic transcription factors using adenoviral vectors carrying three genes: PMB (pancreatic and duodenal homeobox 1 [Pdx1], V-maf musculoaponeurotic fibrosarcoma oncogene homolog A [MafA], and BETA2/NeuroD). METHODS: By direct injection into the intestine through the cranial mesenteric artery, adenoviruses (Ad) were successfully delivered to the entire intestine. After virus injection, we could confirm that the small intestine of the mouse was appropriately infected with the Ad-Pdx1 and triple Ad-PMB. RESULTS: Four weeks after the injection, insulin mRNA was expressed in the small intestine, and the insulin gene expression was induced in Ad-Pdx1 and Ad-PMB compared to control Ad-green fluorescent protein. In addition, the conversion of intestinal cells into insulin-expressing cells was detected in parts of the crypts and villi located in the small intestine. CONCLUSION: These data indicated that PMB facilitate the differentiation of mouse intestinal cells into insulin-expressing cells. In conclusion, the small intestine is an accessible and abundant source of surrogate insulin-producing cells.

The Effect of Nefopam on Postoperative Fentanyl Consumption: A Randomized, Double-blind Study

BACKGROUND: Nefopam is a non-opioid, non-steroidal, centrally acting analgesic drug. The concomitant use of opioids and nefopam is believed to have many advantages over the administration of opioids alone for postoperative pain management. We conducted a randomized, double-blind study to determine the fentanyl-sparing effect of co-administration of nefopam with fentanyl for postoperative pain management via patient controlled analgesia (PCA). METHODS: Ninety female patients who underwent laparoscopic total hysterectomy under general anesthesia were randomized into 3 groups, Group A, fentanyl 1,000 µg; Group B, fentanyl 500 µg + nefopam 200 mg; and Group C, fentanyl 500 µg + nefopam 400 mg, in a total volume of 100 ml PCA to be administered over the first 48 h postoperatively without basal infusion. The primary outcome was total fentanyl consumption during 48 h; secondary outcomes included pain scores and incidence of side effects. RESULTS: Eighty-one patients were included in the analysis. The overall fentanyl-sparing effects of PCA with concomitant administration of nefopam during the first 48 h postoperatively were 54.5% in Group B and 48.9% group C. Fentanyl use was not significantly different between Groups B and C despite the difference in the nefopam dose. There were no differences among the three groups in terms of PCA-related side effects, although the overall sedation score of Group B was significantly lower than that of Group A. CONCLUSIONS: The concomitant administration of nefopam with fentanyl for postoperative pain management may allow reduction of fentanyl dose, thereby reducing the risk of opioid-related adverse effects.

Assessment of chloral hydrate-centered pediatric sedation performed by non-anesthesiologists

BACKGROUND: We aimed to evaluate the efficacy and safety of chloral hydrate-based pediatric sedation conducted by non-anesthesiologists. METHODS: The design and setting of this study was a single-center retrospective study performed at a tertiary university hospital between July 2012 and May 2013. A total of 519 children were enrolled in this study. We investigated the sedation medication, age of patients and type of diagnostic tests or procedures and evaluated the success rate of sedation, sedation/recovery profiles and adverse events. RESULTS: Most patients underwent moderate sedation for diagnostic tests. The most commonly used sedative drug was chloral hydrate, which was solely used for 482 patients. A combination of chloral hydrate/midazolam was used for 24 patients and midazolam only was used for 13 patients. Use of chloral hydrate resulted in a sedation success rate of 65.5% after the initial dose and a success rate of 95.2% with additional doses. The sedation failure rate in children > 6 years was significantly higher than that in children under 6 years. In all patients, the overall onset time and recovery time were too slow and long, respectively, and there was no critical complication. CONCLUSIONS: This study demonstrated that chloral hydrate-based pediatric sedation conducted by non-anesthesiologists was mostly moderate, with a high success rate and a low complication rate. However, the overall onset time and recovery time were too slow and long, respectively. Especially, alternative sedation regimens are required in children > 6 years considering the slower onset time and higher failure rate of sedation.

Consecutive anaphylaxis due to rocuronium and cisatracurium during general anesthesia: A case report

We experienced anaphylaxis during general anesthesia twice in the same patient. After the first incidence of anaphylaxis at the induction of anesthesia, we speculated that the allergen was rocuronium. Thus, we administered sugammadex as well as a vasopressor to treat the anaphylaxis and the vital signs gradually recovered to nearly normal. Thereafter, we could not avoid the administration of another muscle relaxant, cisatracurium, since the patient moved uncontrollably after the surgery was restarted. A second anaphylactic event then occurred. We speculated that the second allergen was cisatracurium and stopped using it. The results of the investigation after the surgery showed that the allergens were indeed rocuronium and cisatracurium. When we encounter anaphylaxis during general anesthesia, it is necessary to suspect all administered medicines as the cause, with the potential of two or more causes, especially with muscle relaxants.

Association between Alcoholism Family History and Alcohol Screening Scores among Alcohol-dependent Patients

OBJECTIVE: Several tests can be used to screen for alcohol dependence (AD), a prevalent disease with a heterogeneous etiology. As some patients with AD have a strong familial tendency in this regard, a family history of alcohol use disorders can affect the outcomes of screening tests and diagnostic evaluations for AD. In this study, we evaluated associations between a family history of alcohol use disorders and evaluations using the Cut down, Annoyed, Guilty, Eye-opener (CAGE) test, Alcohol Use Disorder Identification Test (AUDIT), and Diagnostic and Statistical Manual of Mental Disorders-fourth edition (DSM-IV) diagnostic criteria among patients with AD. METHODS: We recruited 487 male patients with AD from eight hospitals in Korea. Patients were evaluated using the CAGE, AUDIT, and DSM-IV diagnostic criteria. Patients with and without family histories were compared in terms of these assessment tools. RESULTS: Drinking initiation, uncontrollable drinking, and problem drinking occurred earlier and CAGE "annoyed" scores were higher in patients with a family history. Alcohol problems before the age of 25 years, frequency of spontaneous or compulsive alcohol-seeking behavior, and frequencies of psychological dependence and guilt related to alcohol use were also higher. CONCLUSION: Earlier drinking problems, higher scores on specific items of the CAGE, and AUDIT, and meeting more diagnostic criteria indicate more dependent, harmful drinking by patients with AD who have a family history of this condition. Clinicians should consider patients' family history of alcohol use disorders when screening for AD to identify the correct diagnosis and develop appropriate treatment plans for these patients.

Feasibility and Effects of Newly Developed Balance Control Trainer for Mobility and Balance in Chronic Stroke Patients: A Randomized Controlled Trial

OBJECTIVE: To investigate the feasibility and effects of balance training with a newly developed Balance Control Trainer (BCT) that applied the concept of vertical movement for the improvements of mobility and balance in chronic stroke patients. METHOD: Forty chronic stroke patients were randomly assigned to an experimental or a control group. The experimental group (n=20) underwent training with a BCT for 20 minutes a day, 5 days a week for 4 weeks, in addition to concurrent conventional physical therapy. The control group (n=20) underwent only conventional therapy for 4 weeks. All participants were assessed by: the Functional Ambulation Categories (FAC), 10-meter Walking Test (10mWT), Timed Up and Go test (TUG), Berg Balance Scale (BBS), Korean Modified Barthel Index (MBI), and Manual Muscle Test (MMT) before training, and at 2 and 4 weeks of training. RESULTS: There were statistically significant improvements in all parameters except knee extensor power at 2 weeks of treatment, and in all parameters except MBI which showed further statistically significant progress in the experimental group over the next two weeks (p<0.05). Statistically significant improvements on all measurements were observed in the experimental group after 4 weeks total. Comparing the two groups at 2 and 4 weeks of training respectively, 10mWT, TUG, and BBS showed statistically more significant improvements in the experimental group (p<0.05). CONCLUSION: Balance training with a newly developed BCT is feasible and may be an effective tool to improve balance and gait in ambulatory chronic stroke patients. Furthermore, it may provide additional benefits when used in conjunction with conventional therapies.

Health-Related Quality of Life in Breast Cancer Patients with Lymphedema Who Survived More than One Year after Surgery / 한국유방암학회지

PURPOSE: To identify the influence of lymphedema on health-related quality of life (HRQOL) more than 1 year after breast cancer surgery. METHODS: Ninety-six breast cancer patients who survived more than 1 year after surgery and 104 members of the general population were recruited. Patients were divided into 2 groups according to the presence of lymphedema. HRQOL was evaluated with the Short-Form 36-Item Health Survey. RESULTS: There were no statistically significant differences in any scales between groups: groups of breast cancer survivors with and without lymphedema. Compared with the general population, breast cancer survivors had lower quality of life scores in all scales, although the vitality and mental health scales did not differ from chance variation at the 5% level. CONCLUSION: In this study, the presence of lymphedema in breast cancer patients who survived over 1 year after surgery might not affect the quality of life. However quality of life of breast cancer survivors is lower than in general population except for some mental health components.

Correlation between Duration of Dysphagia and Magnetic Resonance Image Findings in Patients with Stroke

OBJECTIVE: To evaluate the correlation between duration of dysphagia and magnetic resonance image (MRI) findings in patients with stroke. METHOD: Ninety seven patients, who were evaluated by video fluoroscopic swallowing studies (VFSS), were recruited for 28 months. They were divided into two groups (transient group (n=52), prolonged group (n=45)) by removing time of NG tube from onset of stroke. Their MRI findings (lesion location and lesion size) were interpreted by one experienced radiologist retrospectively. RESULTS: The duration of dysphagia had statistically significant correlation with lesion size but there was no statistically significant correlation between lesion location and duration of dysphagia in patients with stroke. Compared with transient group (51.5+/-53.8 cm3), a larger lesion was found in prolonged group (95.5+/-107.7 cm3). CONCLUSION: Lesion size, not lesion location, can be a more important factor to predict early removal of NG tube in patients with stroke. More careful interventions about dysphagia are needed in patients with larger stroke lesion.

Association of genetic polymorphisms in the peroxisome proliferator-activated receptor-gamma and methylenetetrahydrofolate reductase with preeclampsia in Korean women / 대한산부인과학회지

OBJECTIVE: To investigate whether polymorphisms of genes encoding peroxisome proliferator-activated receptor-gamma (PPAR gamma) and methylenetetrahydrofolate reductase (MTHFR) are associated with preeclmapsia in Korean women and also to demonstrate whether there is any haplotypic association between preeclampsia and those genes. METHODS: DNA was extracted from whole blood of 226 preeclampsia patients and 235 healthy pregnant women. The genotypes of SNPs in PPAR gamma (-796A>G, P12A (C>G), H447H (161C>T)) and MTHFR (A222V (677C>T), E429A (1298A>C), R594Q (1793G>A)) were analyzed by a single base primer extension assay using a SNaPShot assay kit. Results were analyzed with the Student's t-test, Chi-square test, and Logistic regression analysis. Haplotype analyses were performed using Haploview 3.2 version. RESULTS: There were no significant differences in genotype or allele frequencies of PPAR gamma and MTHFR gene polymorphisms between preeclampsia patients and controls (p>0.05). No increase in the risk of preeclampsia for those genes was observed under any model of inheritance. Among SNPs of the PPAR gamma, MTHFR genes, only SNPs in MTHFR gene (677C>T, 1298A>C, 1793G>A) were in a strong linkage disequilibrium with each other (Lod score>2.0), but there were no significant differences in genotype distribution of haplotypes of MTHFR gene (TAG, CAG, CCA, CCG) between preeclampsia patients and controls (p>0.05). No statistically significant associations were observed between any haplotypes of MTHFR gene and preeclampsia risk. CONCLUSION: This study suggest that SNPs in PPAR gamma and MTHFR gene were not associated with preeclampsia in Korean women, and its haplotypes were also not associated with preeclampsia.

Prenatal diagnosis by isolation of fetal nucleated RBCs in maternal peripheral blood / 대한산부인과학회지

OBJECTIVE: To identify prenatal fetal sex and chromosomal aneuploidies by FISH using isolation of fetal nucleated RBCs. METHODS: peripheral blood samples was collected from 37 women between 11 and 24 weeks of gestation. we tried to enrich nucleated RBCs morphologically by Kleihaur-Betke staining after double gradient centrifugation and magnetic activating cell sorting (MACS) from maternal blood. Fluorescence in situ hybridization (FISH) analyses with CEP X and CEP Y probes for K-B positive nucleated RBCs were performed to detect whether fetal cells were existed among nucleated RBCs by observation of sex chromosomes. RESULTS: The average number of K-B positive nucleated RBCs separated from 10ml of maternal blood was 17.3 (+/-17.2) and the maximum number of nucleated RBCs was 54. We observed FISH signals in nucleated RBCs separated from 18 pregnant women, and Y probe signals were observed in 67.3% of nucleated RBCs separated from 10 pregnant women. CONCLUSION: We confirmed that separated nucleated fetal RBCs can be used to identify fetal sex and chromosomal aneuploidies by FISH. Since nucleated RBCs from maternal origin were not excluded, further studies are needed to overcome this limitation.

Lack of Association between L-myc Single Nucleotide Polymorphism and Cervical Cancer Susceptibility and Invasiveness in Korean Women / 대한산부인과학회지

OBJECTIVE: The aim of this investigation was to analyze the association between a single nucleotide polymorphism (SNP) in L-myc gene (T3109G) and the cervical cancer susceptibility or invasiveness in Korean women. METHODS: The blood samples of 231 cervical cancer patients and 332 non-cancer control subjects who managed at Seoul National University Hospital from 1999 to 2002 were collected. Polymorphism in L-myc (T3109G) was determined using TaqMan method. Allele frequency and genotype distribution in the cervical cancer group were compared with those of the control group to determine whether this polymorphism elevates the susceptibility of Korean women to the cervical cancer. The relationship between this SNP and cancer invasiveness was also evaluated by collating clinicopathologic data of those in the cancer group, such as age, FIGO stage, histologic type, lymph node metastasis and parametrial invasion. RESULTS: In the cervical cancer group, the allele frequency of G was 47.6%, in the control group 48.5%, showing no significant difference (p=0.808). Similarly the genotypes with TG or GG showed no increased risk for the cervical cancer compared with TT genotype. A subgroup analysis of the clinicopathologic parameters in cancer group also showed no significant difference suggesting the lack of an association between SNP of the L-myc and the cervical cancer invasiveness. CONCLUSION: This study shows that Korean women with specific polymorphism in L-myc are neither more susceptible to develop the cervical cancer nor more vulnerable for the cancer progression.

Serum Concentrations of Vascular Endothelial Growth Factor (VEGF) and placental VEGF expression in patients with preeclampsia / 대한산부인과학회지

OBJECTIVE: The goal of this study was to compare serum concentrations of VEGF, placental growth facto r(PlGF), soluble VEGF receptor-1 (sVEGFR-1) and the expression of VEGF-A in placental tissue from preeclamptic pregnancy with normal pregnancy. METHODS: From pregnant women with (n=46) and without (n=40) preeclampsia, maternal serum in third trimester and placental tissue at delivery were collected. The serum concentrations of VEGF, PlGF, and sVEGFR-1 were measured. The expression levels of VEGF-A protein in placenta were assessed using Western blot. RESULTS: The concentrations of total VEGF, PlGF were significantly decreased and that of sVEGFR-1 was significantly increased in patients with preeclampsia. The expression of VEGF-A protein was lower in preeclamptic placenta than in control placenta, but there was no significant difference. CONCLUSION: The abnormality of angiogenic factors (VEGF, PlGF, sVEGFR-1) may be important in the development of pathophysiology of preeclampsia. An elevation of sVEGFR-1 may lead to suppression of VEGF and PlGF effects, and also the down-regulation of VEGF-A protein in placenta may result in the decreased maternal vascular adaptation to pregnancy.

Comparison of Umbilical Venous Erythropoietin Concentration Between Non-meconium Stained Neonates and Meconium Stained Neonates of Term Pregnancy / 대한주산의학회잡지

OBJECTIVE: To determine whether meconium staining can be the indicator of intrauterine hypoxia by comparing umbilical venous erythropoietin (EPO) concentration and the number of nucleated erythrocytes (NRBC), as a marker of intrauterine hypoxia, between non meconium-stained neonates and meconium-stained neonates of term pregnancy. And to determine correlation between the number of NRBC, EPO levels and interleukin-6 (IL-6), as another mediator of intrauterine hypoxia. METHODS: In 240 neonates with gestational age ranged from 37 to 41 weeks, including 231 cases of nonmeconium-stained neonates and 9 cases of meconium-stained neonates, we performed the measurement of EPO levels by RIA, the number of NRBC per 100 white blood cells (WBC) by blood smear and IL-6 by ELISA in umbilical venous blood at delivery. Statistical analysis was performed by chi-square test, Wilcoxon rank sum test, linear regression analysis using SPSS 11.0 version statistical package. RESULTS: Amniotic fluids of meconium-stained neonates had significantly greater EPO concentrations compared with that of nonmeconium-stained controls (41.3+/-13.0 vs 26.5+/-18.9 mIU/mL, p=0.001). But there were no statistical difference in the number of NRBC, IL-6 levels and hematocrit of umbilical venous blood. The EPO levels in umbilical venous blood was correlated with the number of nucleated erythrocytes (r2=7.7%, p<0.001), and IL-6 in umbilical venous blood was correlated with the number of NRBC. (r2=11.5%, p<0.001). CONCLUSION: These results suggest that meconium-stained amniotic fluid can be associated with fetal hypoxia. And the production of fetal NRBC is thought to be stimulated by EPO and IL-6, but it requires further study of other (yet to be determined) hypoxia-derived mediators.

Successful surgical correction of anal atresia in a transgenic cloned piglet

Inbred strains of pig become indispensable for a wide range of biological studies. In biomedical science, it is generally accepted that somatic cell nuclear transfer(SCNT)technology with inbreed strain of pig is essential for xenotransplantation. In this study, we observed the anal atresia in a cloned pig which was derived from fetal fibroblast of inbreed miniature pig. A presumptive anal site of the cloned pig was excised and the rectum was sutured to apposed skin for treatment. This cloned piglet seemed to be normal with healthy status after surgery. This report can be useful for the treatment of anal atresia of cloned piglets.

Clinical Guidelines for Methotrexate in Conservative Treatment for Ectopic Pregnancy / 대한산부인과학회지

OBJECTIVE: To provide more useful guidelines for methotrexate (MTX) treatment in ectopic pregnancy, including patient selection, therapeutic dose, and reproductive outcome. METHODS: Retrospectively, records of 54 patients treated for ectopic pregnancy with systemic MTX were reviewed. MTX was administered 1.0 mg/kg intramuscularly, alternatively with leucovorin 0.1 mg/kg intramuscularly for up to four daily doses of each drug. Samples for beta-hCG detection were obtained on days +3, +7 after beginning of the therapy and then weekly until values were undetectable. RESULTS: 50 patients (92.6%) were treated successfully. 4 patients (7.4%) for whom MTX therapy failed, were treated surgically. The endometrial thickness significantly increased in the failed group, compared to the successful group (14.3+/-4.0 mm vs 7.0+/-2.8 mm, P=0.0001). The serum hemoglobin levels significantly changed in the failed group, compared to the successful group (2.1+/-0.9 g/dL vs 1.0+/-0.8 g/dL, P=0.044). Patients were divided into increasing group and decreasing group according to beta-hCG levels on day 0, that were higher or lower than day -2 level. The resolution time of beta-hCG between increasing group and decreasing group was significantly different (27.6+/-14.0 days vs 17.7+/-8.6 days, p=0.016). In 8 patients (15.1%), an immediate rise of beta-hCG was recorded on day 3 after MTX treatment, but on day 7, a rapid decrease was recorded. Women were treated with significantly different therapeutic dose of MTX according to initial level of serum beta-hCG (p=0.021). There were mild complications (12%). MTX treatment preserved the fallopian tube and thus preserved fertility (70%). CONCLUSION: Systemic MTX use with the dose according to initial level of serum beta-hCG is a safe and highly effective treatment in clinically stable ectopic pregnancy.

Association of the COMT Gene Polymorphism with the Risk of Endometriosis in Korean Women / 대한불임학회지

OBJECTIVE: To investigate whether polymorphism of gene encoding COMT is associated with the risk of endometriosis in Korean women. METHODS: We investigated 136 patients with histopathologically confirmed endometriosis rAFS stage III/IV and 251 control group women who were surgically proven to have no endometriosis. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) of PCR products were done to determine each participant's COMT genotype. RESULTS: The distribution according to NIaIII genetic polymorphisms of COMT were as follows. COMT HH, COMT HL, and COMT LL genotypes were 56.6% (77 women), 34.6% (47 women) and 8.8% (12 women) in the study group and 50.6% (127 women), 39.4% (99 women) and 10.0% (25 women) in the control group. There was no significant difference between the study group and the control group. CONCLUSION: The results suggest that COMT genetic polymorphism may not be associated with the development of endometriosis in Korean women.

Role of Mitogen-Activated Protein Kinase Pathways in the Production of TNF-alpha, IL-10, and MCP-1 by Mycobacterium tuberculosis H37Rv-Infected Human Blood Monocytes

Clinical manifestations of tuberculosis are closely associated with the initial responses of macrophages to mycobacteria. In this study, we investigated the signal transduction pathways for the secretion of cytokines and chemokines [tumor necrosis factor (TNF)-alpha, interleukin (IL)-10, IL-8, and monocyte chemotactic protein-1 (MCP-1)] in human blood monocytes infected with Mycobacterium tuberculosis H37Rv. M. tuberculosis H37Rv infection induced the secretion of significant amounts of TNF-alpha, IL-10, IL-8, and MCP-1 from human blood monocytes. Analysis of mitogen-activated protein kinase (MAPK) activation [extracellular signal-regulated kinase 1/2 (ERK) and p38 kinase] showed rapid phosphorylation of both subfamilies in response to M. tuberculosis H37Rv. Using highly specific inhibitors of p38 (SB203580) and of MEK-1 (U0126 and PD98059), we found that both p38 and ERK were essential for M. tuberculosis H37Rv-induced TNF-alpha production, whereas activation of the p38 pathway, but not that of ERK, was essential for M. tuberculosis H37Rv-induced IL-10 production. Interestingly, the ERK pathway, but not that of p38, was critical for MCP-1 secretion from human blood monocytes infected with M. tuberculosis H37Rv. However, IL-8 secretion was regulated neither by ERK1/2 nor p38 MAPK. Collectively, these results suggest that induction of the MAPK pathway is required for the expression of TNF-alpha. IL-10, and MCP-1 by human blood monocytes during M. tuberculosis H37Rv infection.