First Asian case of biopsy-confirmed manubriosternal joint involvement in rheumatoid arthritis.

Rheumatoid arthritis (RA) is an inflammatory polyarthritis that typically affects the small joints but can also involve the manubriosternal joint (MSJ). Although cases of MSJ involvement in RA are rare, such cases present with chest pain, a mass-like lesion, and subluxation. These cases can also be diagnosed incidentally, while patients are asymptomatic. It is important to differentiate RA involving the MSJ from other diseases such as ankylosing spondylitis that can affect the MSJ. Several cases of RA affecting the MSJ have been reported in Western countries, but none have been reported to date in Asia, especially with disease activity of RA. Here, we report a case of RA in the MSJ that was confirmed by imaging and histological investigation in a middle-aged Asian woman.

Risk factors for Korean women to develop an isthmocele after a cesarean section.

BACKGROUND: The increase in number of cesarean section (CS) operations has resulted in an increase in cases of isthmocele development. The objective of this study is to determine the risk factors for isthmocele development after CS. METHODS: Isthmocele measurements were taken for 404 women with a history of at least one low transverse CS. The following potential risk factors were investigated: patient's age at CS, cause of CS, weeks of gestation at CS, premature rupture of membrane (PROM), phase of labor, type suture (single/double layer), operation time, uterine flexion (anteversion/retroversion), and blood transfusion during operation. A transvaginal ultrasound was carried out to examine the isthmocele in the uterus after CS, including the shape of the isthmocele, residual myometrial thickness, depth and width of isthmocele, cervical thickness, location of the isthmocele, and clinical characteristics. RESULTS: In our study population, the isthmocele had a prevalence of 73.8%. Most isthmocele had a triangular (65.4%) or semicircular shape (10.4%). The presence of an isthmocele was significantly associated with repeat CS, premature rupture of membrane (PROM), short operation time, and extent of cervix dilatation at CS. The risk of isthmocele was low in women who had placenta previa totalis (PPT), twin, a long operation time, or a transfusion during the operation. CONCLUSIONS: In our study, isthmocele development was significantly associated with repeat CS, PROM, a short operation time, and the extent of cervix dilatation at CS. Therefore, PROM prevention and a more careful uterine closure are needed to reduce the risk of developing an isthmocele after CS.

Bone mineral density among Korean females aged 20-50 years: influence of age at menarche (The Korea National Health and Nutrition Examination Survey 2008-2011).

To evaluate a possible correlation between bone mineral density (BMD) and age at menarche, the present study used the BMD dataset of the Korea National Health and Nutrition Examination Survey IV-V (KNHANES IV-V). Age at menarche had a small but significant association with BMD of the lumbar spine in premenopausal Korean females, aged 20-50 years. INTRODUCTION: To investigate any correlation between bone mineral density (BMD) and age at menarche in Korean females using data from the fourth and fifth Korea National Health and Nutrition Examination Survey (KNHANES IV-V; 2008-2011). METHODS: In total, 37,753 individuals participated in health examination surveys between 2008 and 2011. A total of 5032 premenopausal females aged 20-50 years were eligible. Age, height, weight, and age at menarche were assessed. RESULTS: Results from the univariate linear regression and analysis of covariance (ANCOVA) indicated that age (per 1 year), height (per 1 cm), weight (per 1 kg), exercise (per 1 day/week), familial osteoporosis history (yes), parity (n = 0 to ≥4), and menarche age distribution were associated with BMD of the total femur, femur neck, and lumbar spine. After stratifying the bone area and adjusting for age, parity, alcohol intake, smoking, exercise, and familial osteoporosis history, no effect was seen for the total femur or femur neck. Age at menarche 16~17 and ≥18 years groups were associated with BMD of the lumbar spine only. CONCLUSIONS: Age at menarche had a small but significant association with BMD of the lumbar spine in premenopausal Korean females, aged 20-50 years. Females with late menarche may achieve lower peak bone mass at some skeletal sites, which may put them at greater risk for osteoporosis in later life.

Maraviroc decreases CCL8-mediated migration of CCR5(+) regulatory T cells and reduces metastatic tumor growth in the lungs.

Regulatory T cells (Tregs) play a crucial physiological role in the regulation of immune homeostasis, although recent data suggest Tregs can contribute to primary tumor growth by suppressing antitumor immune responses. Tregs may also influence the development of tumor metastases, although there is a paucity of information regarding the phenotype and function of Tregs in metastatic target organs. Herein, we demonstrate that orthotopically implanted metastatic mammary tumors induce significant Treg accumulation in the lungs, which is a site of mammary tumor metastasis. Tregs in the primary tumor and metastatic lungs express high levels of C-C chemokine receptor type 5 (CCR5) relative to Tregs in the mammary fat pad and lungs of tumor-free mice, and Tregs in the metastatic lungs are enriched for CCR5 expression in comparison to other immune cell populations. We also identify that C-C chemokine ligand 8 (CCL8), an endogenous ligand of CCR5, is produced by F4/80(+) macrophages in the lungs of mice with metastatic primary tumors. Migration of Tregs toward CCL8 ex vivo is reduced in the presence of the CCR5 inhibitor Maraviroc. Importantly, treatment of mice with Maraviroc (MVC) reduces the level of CCR5(+) Tregs and metastatic tumor burden in the lungs. This work provides evidence of a CCL8/CCR5 signaling axis driving Treg recruitment to the lungs of mice bearing metastatic primary tumors, representing a potential therapeutic target to decrease Treg accumulation and metastatic tumor growth.

Enhanced efferocytosis by dendritic cells underlies memory T-cell expansion and susceptibility to autoimmune disease in CD300f-deficient mice.

Homeostasis requires the immunologically silent clearance of apoptotic cells before they become pro-inflammatory necrotic cells. CD300f (CLM-1) is a phosphatidylserine receptor known to positively regulate efferocytosis by macrophages, and CD300f gene-deficient mice are predisposed to develop a lupus-like disease. Here we show that, in contrast to CD300f function in macrophages, its expression inhibits efferocytosis by DC, and its deficiency leads to enhanced antigen processing and T-cell priming by these DC. The consequences are the expansion of memory T cells and increased ANA levels in aged CD300f-deficient mice, which predispose CD300f-deficient mice to develop an overt autoimmune disease when exposed to an overload of apoptotic cells, or an exacerbated autoimmunity when combined with FcγRIIB deficiency. Thus, our data demonstrates that CD300f helps to maintain immune homeostasis by promoting macrophage clearance of self-antigens, while conversely inhibiting DC uptake and presentation of self-antigens.

Rapid enlargement of endometrial stromal sarcoma after uterine fibroid embolization for presumed adenomyosis: a case report and literature review.

Uterine sarcomas have rarely been diagnosed after uterine artery embolization. It remains unclear whether the diagnostic work-up is required prior to such embolization to prevent a missed diagnosis of sarcomas and a delay in providing definitive treatment. Because of the rarity and heterogeneity of endometrial stromal neoplasms, little is known about their epidemiology, pathogenesis, and molecular pathology. The authors report a case of low-grade endometrial stromal sarcoma (ESS) diagnosed after uterine fibroid embolization. Although they performed laparoscopic biopsy of the rapidly growing uterine mass, they could not detect the ESS. Although rare, ESS should be considered in the differential diagnosis of uterine fibroid enlargement. It is essential to assess the risk of malignancy by taking into account the patient's clinical symptoms, results of the physical exam, and imaging findings prior to uterine artery embolization. Pathologic diagnosis should include an adequate biopsy sample and the use of molecular genetic testing.

Ferritin is associated with neural differentiation of bone marrow-derived mesenchymal stem cells under extremely low-frequency electromagnetic field.

Extremely low-frequency electromagnetic field (ELFEF) is a well-known mechanical stimulation that induces neural differentiation. It is potentially an effective treatment for neurodegenerative diseases. In a previous study, ferritin light chain was upregulated in ELFEF-exposed human bone marrow-derived mesenchymal stem cells (BM-MSCs). Ferritin light chain is a component of ferritin, a highly conserved iron-binding protein. In this study, to identify molecules associated with ferritin during neural differentiation of BM-MSCs, we performed reverse transcription polymerase chain reaction (RT-PCR), western blotting, and ATP analysis. Our data indicated that ELFEF triggers the upregulation of ferritin light chain (FLC) and ferritin heavy chain (FHC) in BM-MSCs. The elevated levels of FLC and FHC correlated positively with the differentiation of BM-MSCs into neural cells. Moreover ELFEF induced the activation of iron regulatory protein-1 (IRP-1) and cofilin, which are downstream targets of ferritin. These results suggest that ELFEF induces neural differentiation through activation of a ferritin-regulated mechanism.

Early hematological effects of chemo-radiation therapy in cancer patients and their pattern of recovery - A prospective single institution study.

UNLABELLED: The purpose of this prospective study is to understand the early hematological effects of chemo-radiation therapy in cancer patients, their pattern of recovery and to ascertain their prognostic value. METHODS: 255 diagnosed cancer patients planned for definitive treatment with radiation therapy alone or with chemotherapy were included in this two year prospective study. A complete blood count was done at baseline, weekly during the course of therapy and thereafter, monthly for a period of 6 months. For the purpose of grading clinical toxicity, the Common Toxicity Criteria, CTCAE v2.0 was used while RECIST criteria was used to define the tumor response rates. This study was statistically analyzed using SPSS software. RESULTS: 255 patients were included in the study wherein head and neck cancers comprised the major patient population (28.6%) followed by cervix (18.8%) and breast (15.7%). Out of these, 37% in head-and-neck cancer subgroup, and 58.3% in cervix had anemia at start of treatment. 92.2% cases with chemoradiation developed anemia during treatment, while with radiation alone it was 95.5%. This was statistically significant in patients with cancer uterine cervix (p 〈 0.01). At the end of treatment 65% patients with normal hemoglobin had complete responses (CR), while 58.3% with mild anemia and 33.3% with moderate anemia had CR (p=0.1). CONCLUSIONS: Severe anemia during treatment is a poor prognostic indicator and is usually a sign of advanced disease. Leucopenia and thrombocytopenia occur more commonly during chemoradiotherapy as against radiotherapy alone, but improves with supportive management.

Rate and associated factors of solifenacin add-on after tamsulosin monotherapy in men with voiding and storage lower urinary tract symptoms.

AIM: To explore the rate of add-on therapy with solifenacin in men with voiding and storage lower urinary tract symptoms (LUTS) after tamsulosin monotherapy and to explore predictive factors for starting solifenacin add-on therapy. METHODS: Men aged ≥ 45 years with IPSS ≥ 12 and symptoms of OAB (OAB-V8 ≥ 8, micturition ≥ 8/24 h, urgency ≥ 2/24 h) were enrolled to receive tamsulosin 0.2 mg once daily. After 4 weeks, men with residual symptoms of OAB and reported 'dissatisfied' or 'a little satisfied' were received solifenacin 5 mg in combination with tamsulosin monotherapy. Subjects completed an IPSS, a Quality of life (QoL) index, OAB V8, and an International Consultation of Incontinence Questionnaire (ICIQ)-Male LUTS, and patient perception of bladder condition (PPBC) at baseline and week 4. RESULTS: Of a total of 305 patients, 254 patients completed 4 weeks of tamsulosin treatment. For 176 patients, solifenacin was added (69.3%). Significant predictive factors of solifenacin add-on therapy included long LUTS duration, high IPSS, number of micturitions per 24 h, more urgency episodes, high urgency severity score in a voiding diary and high OAB V8 score. Based on multivariable analysis, potential predictive factors of solifenacin add-on therapy included long LUTS duration (OR = 1.008, 95% CI: 1.001-1.014), high serum PSA (OR = 1.543, 95% CI: 1.136-2.095) and small prostate size (OR = 0.970, 95% CI: 0.947-0.994) (p < 0.05). IPSS, daytime micturitions and urgency episodes, OAB V8 scores, ICIQ and PPBC were improved after tamsulosin monotherapy. CONCLUSIONS: Two thirds of men with voiding and storage LUTS needed to add anticholinergics after 4 weeks of tamsulosin monotherapy. Patients with longer lasting symptoms and storage symptoms with small prostate volume may require the anticholinergic add-on.

Superior vena cava obstruction (SVCO) in patients with advanced non small cell lung cancer (NSCLC).

INTRODUCTION: To report on prognostic and treatment factors influencing the response of SVCO and related survival outcomes in advanced non small cell lung cancer. MATERIAL AND METHODS: From November 2008 through December 2011, 18 consecutively diagnosed NSCLC patients with SVCO were included in this study. The patient, tumor and treatment related factors were analyzed. Median overall survival (OS), Kaplan -Meier survival plots, T-test, Cox Proportional Hazards models were generated by multiple covariates (MVA) and analyzed on SPSS software (version 19.0; SPSS, Inc., Chicago, IL). RESULTS: Thirteen patients (72%) had presented with SVCO before the pathological diagnosis of underlying lung malignancy, while 5 (28%) progressed to SVCO after initiating treatment with chemotherapy. Twelve (68%) patients achieved subjective relief from the obstruction at the completion of palliative radiation therapy. Treating oncologists preferred 4 Gy per fraction in 11 (62%), while the median biologically equivalent dose delivered was 28 Gy. Six (33%) patients received chemotherapy during the course of treatment. Median OS of the entire cohort was 3±1.85mths and 1-year survival rate of 7%. Univariate analysis confirmed that SVCO patients with good performance score (p=0.02), and partial response to chemotherapy (p= 0.001) have superior OS. However, Cox regression modeling for MVA demonstrated only good performance SVCO patients (p = 0.05) have a better OS. CONCLUSION: RT effectively relieves SVCO but overall poor survival associated in our clinical scenario needs to be improved with multimodality approach. Adjuvant chemotherapy is to be considered after initial radiation therapy in good performance patients. KEYWORDS: superior vena cava obstruction (SVCO), radiation therapy, chemotherapy, non small cell lung cancer (NSCLC), BED (biologically equivalent dose).

A case of a borderline mucinous tumor of the ovary with sarcoma-like mural nodules producing granulocyte colony-stimulating factor.

Borderline ovarian tumor with sarcoma-like mural nodule is rare. Malignant mural nodules usually occur in the wall of an atypical proliferative mucinous tumor or a mucinous carcinoma. The authors report one case of unfavorably progressive borderline tumor of the ovary with sarcoma-like mural nodule that produced granulocyte colony-stimulating factor (G-CSF).

Whole saliva physico-biochemical changes and quality of life in head and neck cancer patients following conventional radiation therapy: a prospective longitudinal study.

BACKGROUND: We investigated the physico-biochemical changes in saliva and its relation to quality of life (QOL) in head and neck cancer patients following conventional radiation therapy (RT). MATERIALS AND METHODS: 53 consecutive head and neck cancer patients underwent conventional RT using telecobalt photons. We analyzed objective sialometry and sialochemical parameters of salivary gland function and a physician reported Oral Assessment Protocol to assess the patients' QOL during (baseline, 3 and 6 weeks) and post RT (3 and 6 months). Statistical analysis was done using SPSS software (version 15.0; SPSS, Inc., Chicago, IL, USA). RESULTS: Stimulated salivary flow rates had shown a consistent decline during and in post-RT analysis (P < 0.001). A significant correlation was seen between mean salivary flow rates at 6 months post-RT and mean salivary electrolytes and amylase levels during the same period (P < 0.001). Mean global QOL scores had significantly worsened during RT and were still significantly poorer at 6 months than initial pre-RT levels (P < 0.001). Further, significant correlation was established between salivary pH values with global QOL scores at 6 months (P = 0.05). CONCLUSIONS: Radiation-induced hyposalivation invariably persists and correlates with poor global QOL scores seen during and following conventional RT. Post RT, there is a trend for biochemical reversal toward pre-irradiation levels suggesting a subsiding inflammation or a probable functional recovery.

Clinical analysis of borderline ovarian tumors.

PURPOSE: The goal of this study was to evaluate the incidence and clinical features of borderline ovarian tumors (BOTS). METHODS: We retrospectively performed chart reviews of 22 patients with BOTS who were diagnosed and treated in the university medical center from 1998 to 2009 inclusively. RESULTS: BOTS among ovarian pathology in our hospital were detected in 22 patients (1.79%). The mean age was 50 years, range (20-90). Post surgical FIGO staging was Stage I = 86.4%, and Stage II = 13.6%. The most common histologic subtype was mucinous (59%). Five patients (22.7%) had a unilocular cyst at ultrasonography. Conservative surgery was performed in 31.8%. One patient of them had normal spontaneous delivery after term pregnancy. Two patients had a recurrence. One patient with recurrent disease underwent transformation to invasive cancer and died 35 months after the initial diagnosis. CONCLUSION: Clinicians should warn patients about the early relapse of BOTS and these patients may need careful follow-up due to the possibility of recurrences.

A case of primary ovarian adenomyoma mimicking ovarian malignancy.

Adenomyoma is a benign tumor composed of smooth muscle and benign endometrium. These tumors typically originate within the uterus. An extrauterine adenomyoma is an extremely rare entity. After an extensive literature search, only four cases of primary ovarian adenomyoma appear to have thus far been reported. Here, we report a case of ovarian adenomyoma in a 39-year-old woman mimicking malignant neoplasma of the ovary, along with a brief literature review.

Comparison of environmental radiation monitoring programs in China and the United States.

The monitoring of environmental radiation has been carried out across the United States by the U.S. Environmental Protection Agency's RadNet (formerly the Environmental Radiation Ambient Monitoring System, ERAMS) and the Global Network Program (GNP) of the Environmental Measurements Laboratory (EML), and in the People's Republic of China (PRC) by their National Radioactivity Contamination Monitoring System (NRCMS). It is expected that an awareness of the similarities and differences in the structure and operation of these programs will prove helpful to both countries and perhaps others as they continue to develop their monitoring capabilities.

Gene expression profiles in squamous cell cervical carcinoma using array-based comparative genomic hybridization analysis.

Our aim was to identify novel genomic regions of interest and provide highly dynamic range information on correlation between squamous cell cervical carcinoma and its related gene expression patterns by a genome-wide array-based comparative genomic hybridization (array-CGH). We analyzed 15 cases of cervical cancer from KangNam St Mary's Hospital of the Catholic University of Korea. Microdissection assay was performed to obtain DNA samples from paraffin-embedded cervical tissues of cancer as well as of the adjacent normal tissues. The bacterial artificial chromosome (BAC) array used in this study consisted of 1440 human BACs and the space among the clones was 2.08 Mb. All the 15 cases of cervical cancer showed the differential changes of the cervical cancer-associated genetic alterations. The analysis limit of average gains and losses was 53%. A significant positive correlation was found in 8q24.3, 1p36.32, 3q27.1, 7p21.1, 11q13.1, and 3p14.2 changes through the cervical carcinogenesis. The regions of high level of gain were 1p36.33-1p36.32, 8q24.3, 16p13.3, 1p36.33, 3q27.1, and 7p21.1. And the regions of homozygous loss were 2q12.1, 22q11.21, 3p14.2, 6q24.3, 7p15.2, and 11q25. In the high level of gain regions, GSDMDC1, RECQL4, TP73, ABCF3, ALG3, HDAC9, ESRRA, and RPS6KA4 were significantly correlated with cervical cancer. The genes encoded by frequently lost clones were PTPRG, GRM7, ZDHHC3, EXOSC7, LRP1B, and NR3C2. Therefore, array-CGH analyses showed that specific genomic alterations were maintained in cervical cancer that were critical to the malignant phenotype and may give a chance to find out possible target genes present in the gained or lost clones.

Identification of differentially expressed genes using annealing control primer-based GeneFishing in human squamous cell cervical carcinoma.

AIMS: To compare different gene expression patterns between squamous cell cervical carcinoma (SCC) and normal cervical tissue in Korean women and to identify those genes that are specifically or predominantly expressed in SCC by employing annealing control primer (ACP)-based GeneFishing polymerase chain reaction (PCR). MATERIALS AND METHODS: Cervical cancer specimens were obtained from patients enrolled at the Department of Obstetrics and Gynecology, Kang Nam St. Mary's Hospital, Catholic University of Korea. We used a common reference that was mixed with an equal amount of RNA extracted from patients without cervical cancer. The profiles of expressed genes were compared between the SCC and normal cervix identified using GeneFishing differentially expressed gene kits, screened by a BLAST search, and confirmed by semi-quantitative reverse transcription-PCR (RT-PCR). RESULTS: Almost 100 differentially expressed genes were identified in the control and SCC samples. Using 60 arbitrary ACPs, 50 differentially expressed genes were identified, and 30 up-regulated and 20 down-regulated expressed genes were sequenced. Among 50 clones selected by ACP-based GeneFishing PCR, six genes with different expression patterns were determined and confirmed by semi-quantitative RT-PCR. The functional roles of two up-regulated genes, fibrillarin and calgranulin A, and one down-regulated gene, clusterin, were previously identified. However, the functional roles of two up-regulated genes and one down-regulated gene were not identified. CONCLUSION: We identified distinctive gene expression profiles in Korean women with SCC using ACP-based GeneFishing PCR.

Ontogeny of gonadotropin releasing hormone-containing neurons in the teleost brain.

We investigated changes in two gonadotropin releasing hormone (GnRH)-containing neuronal populations during juvenile development in the African teleost, Haplochromis burtoni. Juveniles were sampled at weekly intervals and GnRHir neurons were identified through immunocytochemistry (ICC), then counted and measured on computer-captured video images. Soma size of GnRH neurons in the preoptic area (POA), which regulate gonadotropin release from the pituitary, is socially modulated in adults. Here we show that in juveniles the soma size of these neurons increases as a linear function of body weight. Terminal nerve (TN) GnRHir neurons, in contrast, are not involved in pituitary regulation and their soma size is not socially modulated in adults. In juveniles, soma size of these neurons is a quadratic function of body size and the covariance of soma size and body size is much less than in the POA GnRHir neurons. In both populations, GnRHir neuronal number covaries with body size or age only in the earliest juvenile stages. Analysis of the development of these two distinct GnRHir neuronal populations provides insight into their functional differentiation in adults.

Dynamic process captured on a single image: an approach to screening for abnormal superior vena caval flow.

A strategy for displaying and archiving dynamic quantitative data from scintigraphic imaging is described and applied to diagnosing obstructed thoracic veins. A prospective series of 25 patients with concurrent radiographic contrast and tracer venograms along with 49 controls showed a 33% sensitivity, comparable to previously published data. The use of first harmonic Fourier analysis enhanced the screening value of the test by identifying all abnormals. Moreover, this format captured the dynamic physiologic data on a single photograph. This technique is readily available to nearly any nuclear imaging laboratory equipped with a gamma camera and a computer.