Search

BACKGROUND: Cardiovascular disease is one of the main causes of mortality in patients with chronic obstructive pulmonary disease (COPD), and atherosclerosis is a cause of cardiac comorbidities in COPD. However, it is not clear whether airflow limitation is associated with atherosclerosis irrespective of smoking.OBJECTIVE: To investigate whether airflow limitation is independently associated with vascular stiffness.METHODS: We enrolled 18 893 participants (male 70.5%; mean age 47.5 ± 9.8 years; never smokers 44.2%) who underwent spirometry and brachial-ankle pulse wave velocity (baPWV) as part of a standard health examination at Ajou University Hospital, Suwon, South Korea, from January 2010 to December 2015.We defined vascular peripheral atherosclerosis as baPWV ≥ 1400 cm/s and airflow limitation as pre-bronchodilator ratio of forced expiratory volume in 1 sec (FEV1) to forced vital capacity (FVC) RESULTS: Mean baPWV was higher in subjects with airflow limitation (1477.6 ± 331.7 cm/sec, n = 638) than in those without airflow limitation (1344.1 ± 231.8 cm/sec, n = 18255, P < 0.001). In multivariate logistic regression analysis, the following were independent predictors associated with peripheral atherosclerosis (P < 0.05): age, male sex, fasting serum glucose, mean blood pressure, serum leukocyte count, serum low density lipoprotein level and FEV1.CONCLUSION: Airflow limitation was an independent predictor of vascular stiffness irrespective of smoking history, which suggests that airflow limitation is linked with atherosclerosis.

The existences of protein are important to supply nutritional requirements and to support optimal growth performance in modern broiler chicken. The present experiment was conducted to evaluate the effect of purified amino acid (PAA) isolated from animal blood on growth performance and immune response. A total of one hundred of 1-day old broiler chicken were used in the experiment, following a completely randomized design of 4 groups of treatment differed in concentrations of PAA supplementation (T1: control, no PAA addition; T2: 0.05%; T3: 0.1%; and T4: 0.5%) with 4 replicates for each group. Levels of various cytokines, such as IgA, IgG, interleukin (IL)-2, IL-6, tumor necrosis factor α, and interferon γ, were analyzed using an ELISA kit. Insulin-like growth factor 1, an important growth hormone, was also examined using an ELISA kit. The present result showed feed efficiency and average daily feed intake of broiler chicken increased significantly along with increasing concentrations of PAA (P

The use of calcium phosphate bone cement has been described to allow for retention of reduction. Therefore, we evaluated whether augmentation with resorbable calcium phosphate could improve fracture stability in osteoporotic hip fractures. The results showed that augmentation with calcium phosphate cement significantly improved the stability of intertrochanteric fractures. The aim with this study was to measure whether augmentation with resorbable calcium phosphate cement could improve fracture stability in osteoporotic hip fractures. We retrospectively reviewed 82 patients who underwent closed reduction and internal fixation with proximal femoral nail (PFN) for unstable intertrochanteric fractures between 2014 and 2017. In 42 of 82 patients, patients were treated with a PFN alone (group I). These patients were compared with 40 patients for whom the same device combined with calcium phosphate cement for augmentation was used (group II). Questionnaire surveys or telephone interviews were conducted and patients completed a self-report Harris hip score (HHS) and visual analog scale (VAS) scores. Radiographic outcomes including mean sliding distance of screw, femoral shortening, and varus collapse were compared. Postoperative complications were compared. Clinical outcomes at 6 months after surgery were equivalent in both groups. Screw sliding, femoral shortening, and varus collapse were all significantly reduced in the cemented group at the last follow-up (p

The age and growth of conger eel, Conger myriaster, were investigated by measuring transversely sectioned sagittal otoliths samples from 635 individuals. Sample ages ranged from 1 to 13 years in the female data. Parameters of the von Bertalanffy growth function were estimated using nonlinear regression from back-calculation, mean length of samples at age relationships, and otolith weight-at-age relationships. Best-fitting value of the three methods was the otolith weight-at-age relationship (r2 = .87). Parameters of otolith weight-at-age were estimated as L∞ = 143.76 cm, K = 0.081, and t0 = −1.285. Maximum oocyte diameter (MOD) ranged from 50 to 430 μm. Reproductive traits of ovaries showed a positive relationship between GSI and MOD (r2 = .8515). It is suggested that oogenesis begins to develop from 4 years of age and at lengths of about 45 cm TL. In conclusion, these data provide reliable fundamental data for the fish stock management of Conger myriaster in South Korea.

Background: It has been suggested that AF-related ischemic stroke (IS) that is accompanied by atherosclerotic burden have poorer outcomes. The aim of this study was to investigate the importance of pre-stroke glycemic control (PSGC) on the early neurologic deterioration (END) of patients with acute AF-related IS. Methods: We retrospectively recruited 121 patients with AF-related IS who also had Diabetes mellitus (DM). The HbA1C level was measured in all subjects. END was defined as an increase in the National Institute of Health Stroke Scale (NIHSS) score of 4 NIHSS points within 7days of symptom onset compared to the initial NIHSS score. Results: In this study, 20.7% (25 patients) were classified as having a poor PSGC status with a HbA1C level above 8.0%. In the univariate analysis, a poor PSGC status (p

Background A multidrug regimen including isoniazid, rifampicin, pyrazinamide, and ethambutol is commonly used as a first-line treatment for tuberculosis. However, these regimens can occasionally result in severe adverse drug reactions such as drug rash with eosinophilia and systemic symptoms (DRESS) syndrome and drug-induced liver injury. The culprit drug and mechanistic basis for the hypersensitive reaction are unknown. Objective To investigate drug-specific T-cell responses in patients with ATD-induced cutaneous hypersensitivity and its underlying mechanism. Methods In total, we enrolled 8 patients with ATD-induced maculopapular exanthema and DRESS, and performed lymphocyte transformation test. Subsequently, drug-specific T-cell clones were generated from four of the patients who showed proliferation in response to ATDs. We measured the drug-specific proliferative responses and counted the drug-specific, interferon-gamma (IFN-γ)/granzyme B -producing cells after drug stimulation. Anti-human class I and class II blocking antibodies were used to analyze human leukocyte antigen (HLA)-restricted T-cell responses. Results Positive proliferative responses to ATDs were mostly found in patients with cutaneous hypersensitivity. Furthermore, we isolated isoniazid/rifampicin -specific T-cells from patients, which consisted primarily of CD4+ T-cells. Drug-specific CD4+ T-cells proliferated and secreted interferon gamma (IFN-γ)/granzyme B when stimulated with isoniazid or rifampicin, respectively. Isoniazid-responsive T-cell clones did not proliferate in the presence of rifampicin, and vice versa. Drug-specific T-cell responses were blocked in the presence of anti-human class II antibodies. Conclusions This study identifies the presence of isoniazid/rifampicin-specific T-cells in patients with ATD-induced maculopapular exanthema and DRESS. Furthermore, it highlights the important role of drug-specific T-cell immune responses in the pathogenesis. This article is protected by copyright. All rights reserved.

Background Relationship between AF and inflammation was shown in previous studies. However, there was limited data about the association between the acute hepatitis B flare (AVHF-B) and AF in the long-term follow-up. Purpose The aim of this study was to evaluate the association of AVHF-B and long-term clinical outcomes in patients with AF. Methods Our University echocardiography, electrocardiogram (ECG) and hepatitis B database were reviewed from 2008 to 2017 to identify patients with AF and AVHF-B. Patients were followed for a mean 26.4±0.9 months and were divided into two groups according to the absence or presence of AVHF-B with AF. Results Among 280 patients with AF, 100 (35.7%) patients had AVHF-B. Total any event rates were significantly higher in patients with AVHF-B compared to those without AVHF-B (P Conclusion The patients with AVHF-B were associated with higher arrhythmic events and total any events, suggesting more intensive medical therapy with close clinical follow-up will be required. Acknowledgement/Funding None

Background There was limited data about the association between the electrocardiographic characteristics and irreversible fulminant hepatitis (IFH) in patients with acute hepatic failure (AHF) in the long-term follow up. Purpose The aim of this study was to analysis the electrocardiographic characteristics for prediction of IFH in patients with AHF. Methods Our University echocardiography, electrocardiogram (ECG) and viral hepatitis database were reviewed from 2008 to 2017 to identify patients with AHF. Patients were followed for a mean 32.0±0.8 months and were analyzed to find out the predictors for IFH. Results Among 202 patients with AHF, 23 (11.4%) patients had IFH. In our study, there are 118 (58.7%) viral hepatitis patients (hepatitis A, 83 patients, 41.3%; hepatitis B, 19 patients, 9.5%; hepatitis C, 15 patients, 7.5%) and alcoholic hepatitis patients (83 patients, 41.3%). Based on the ROC curve, we set the corrected QT interval (QTc) cutoff value of 425 msec for prediction of IFH, which gave a sensitivity of 66.7% and a specificity of 66.0% (P=0.002). In univariate analysis, age, QTc, diabetes mellitus (DM), heavy alcoholics, labile INR, hemoglobin, albumin, total bilirubin, sodium, and c-reactive protein were significantly associated with IFH. In multivariate analysis, age, QTc, DM, heavy alcoholics, and total bilirubin were independent risk factors for IFH at the long-term follow-up. Conclusion Longer QTc (>425msec) in patients with AHF was associated with higher IFH, suggesting close clinical and electrocardiographic follow-up will be required. Acknowledgement/Funding None

Continuous interscalene block is an approved modality for postoperative pain control, but it may cause hemidiaphragmatic paresis. In this study we aimed to determine whether continuous supraclavicular block would provide postoperative analgesia comparable to that of continuous interscalene block and reduce the incidence of hemidiaphragmatic paresis. Patients scheduled for open rotator cuff repair were randomly allocated to receive continuous interscalene (n = 38) or supraclavicular block (n = 37). Both participants and assessing clinicians were blinded to the group allocation. The primary endpoint was the mean pain intensity 24 h after the surgery. Postoperative mean (SD) pain scores at 24 h were similar in the supraclavicular and interscalene groups (2.57 (1.71) vs 2.84 (1.75) respectively; p = 0.478). The incidence of complete or partial hemidiaphragmatic paresis was lower in the supraclavicular group at 1 h after admission to the postanaesthetic care unit and 24 h after the surgery [25 (68%) vs 38 (100%); p = 0.001 and 14 (38%) vs 27 (71%) respectively; p = 0.008]. Continuous supraclavicular block provided comparable analgesia compared with interscalene block with a reduced incidence of complete or partial hemidiaphragmatic paresis for 24 h following surgery.

Background BOLERO-2 phase III trial established the efficacy of everolimus (EVE) plus exemestane (EXE) for the treatment of postmenopausal patients with hormone receptor (HR)-positive, HER2-negative, advanced breast cancer (aBC). However, in this study only a minority ( Methods EVEREXES is an open-label phase IIIb, single arm, multi-center trial, which from March 2013 to October 2014 enrolled 232 post-menopausal, HR-positive and HER2-negative, aBC patients previously treated with aromatase inhibitors, across 13 countries in Asia Pacific, Middle East, North and South Africa, with a significant majority of patients being of Asian ethnicity (196, 84.5%). Its primary objective was to investigate the safety and tolerability profile of EVE+EXE. Secondary objectives were the evaluation of efficacy (assessed by PFS, ORR, and CBR based on RECIST 1.1 criteria) and change in ECOG performance status. Results At data cut off of 31st of January 2015, at a median follow up of 11.7 months, median PFS for the ITT population was 9.5 months [9.2-11.6 months], based on local assessment, with the observation of 1 (0.4%) CR and 35 (15.4%) PR. Regarding safety and tolerability, a majority (81.1%) of grade (G) 1/2 adverse events (AEs) was reported. In particular, the following pattern was observed in terms of % of patients who developed G1/G2/G3 mTOR-inhibition induced AEs: stomatitis (36.1, 13.7, 10.6), rash (21.6/6.2/0), fatigue (10.6, 4.4, 2.2), hyperglycemia (6.2, 11.5, 7.0), weight decrease (7.5, 7, 0.9), pneumonitis (5.7, 7, 0.9). No Grade 4 AEs related to EVE+EXE treatment were observed, with exception of one case of non infectious pneumonitis (0.4%). Median dose intensity of everolimus was 9.2 mg/day. Conclusions Efficacy and safety results from EVEREXES trial further confirm the role of EVE+EXE for the treatment of HR+/Her2- advanced BC patients in Eastern countries. Results were consistent with data previously reported in BOLERO-2 trial. Citation Format: Im Y-H, Uslu R, Lee KS, Nagarkar R, Sohn J, Sevinc A, Altundag K, Chang Y-C, Abdel-Razeq H, Im S-A, Jeong J, Park HY, Arpornwirat W, Bastick P, Le TH, Ocak Arikan O, Xue HL, Canatar A, Valenti R, Kim S-B. Clinical effectiveness of everolimus and exemestane in advanced breast cancer patients from Asia and Africa: First efficacy and updated safety results from the phase IIIb EVEREXES study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-13-09.

Background:Currently, most authors accept that mixed connective tissue disease (MCTD) is an independent entity, although there are those who argue that it is actually an overlap syndrome or an undifferentiated early phase of another systemic autoimmune disease (SAD).Objectives:To analyze the long term evolution of a serie of patients with MCTD.Methods:Observational, retrospective and multicenter study in patients with MCTD (diagnostic criteria of Alarcón-Segovia et al),followed for a minimun of 2 years.Results:Fifty-five patients (49 women) with a median age at diagnosis of 38±14 years and with a follow up time (median) of 101 months (range, 24-237 months with a total of 501.2 pacients-year) were identified.At the end of the follow-up period, only 27% (15/55) of the patients kept on fulfilling MCTD criteria. In the remaining 73% (40), 40% (22) had been differentiated to systemic lupus erythematosus (SLE), 13% (7) to systemic sclerosis (SSc) and 20% (11) developed an overlap syndrome [SSc+SLE in 8 cases and SSc+rheumatoid arthritis (AR) in 3]. In 8% of these patients, a secondary Sjögren’s syndrome was diagnosed during the follow-up period. The average score in patients who met the EULAR/ACR 2013 criteria for SSc was 11 (minimum 9 - maximum 16) and the average time elapsed from the diagnosis of MCTD to meet SSc criteria was 64.4 months (interquartile range [IQR] 25-75%: 10-127 months).Applying the 2012 SLICC criteria, only 24 patients of those initially diagnosed as MCTD ended up meeting SLE criteria. The average score in these patients was 5.6 (4-9) and the average time elapsed from the diagnosis of MCTD unltil fulfilling the SLICC criteria was 39 months (IQR 25-75%: 6-28). When we apply the new ACR/EULAR 2019 criteria, the percentage of patients who meet SLE criteria increased to 30%, with an average score of 17.3 (10-38). The average time elapsed since the diagnosis of MCTD until meeting the new SLE criteria was reduced to 17 months (IQR 25-75: 0-10).In the multivariate study, the presence of sclerodactyly (OR: 2.91; IC 95% 1.90 - 4.1, p= 0.001) and esophageal involvement (OR: 2.05; IC 95% 1.14–3.66, p=0.016) were associated with the evolution to SSc. Any predictor of evolution to SLE was identified.Conclusion:Only slightly more than a quarter of patients initially diagnosed as MCTD maintain this diagnosis during the follow-up. The majority, ended up evolving towards to another SAD, fundamentally SLE and SSc. The new ACR/EULAR 2019 criteria seems to be more sensitive than the SLICC 2012 criteria for diagnose SLE in these patients.Disclosure of Interests:L Montolio-Chiva: None declared, J. Narváez: None declared, Maria Pascual: None declared, Hye Sang Park: None declared, Ana V Orenes Vera: None declared, Eduardo Flores: None declared, Juanjo J Alegre-Sancho Consultant of: UCB, Roche, Sanofi, Boehringer, Celltrion, Paid instructor for: GSK, Speakers bureau: MSD, GSK, Lilly, Sanofi, Roche, UCB, Actelion, Pfizer, Abbvie, Novartis, Iván Castellví: None declared, Joan Miquel Nolla: None declared

Many of the effects of resveratrol are consistent with the activation of AMP-activated protein kinase (AMPK), silent information regulator T1 (SIRT1) and peroxisome proliferator-activated receptor (PPAR)γ co-activator 1α (PGC-1α), which play key roles in the regulation of lipid and glucose homeostasis, and in the control of oxidative stress. We investigated whether resveratrol has protective effects on the kidney in type 2 diabetes.Four groups of male C57BLKS/J db/m and db/db mice were used in this study. Resveratrol was administered via gavage to diabetic and non-diabetic mice, starting at 8 weeks of age, for 12 weeks.The db/db mice treated with resveratrol had decreased albuminuria. Resveratrol ameliorated glomerular matrix expansion and inflammation. Resveratrol also lowered the NEFA and triacylglycerol content of the kidney, and this action was related to increases in the phosphorylation of AMPK and the activation of SIRT1-PGC-1α signalling and of the key downstream effectors, the PPARα-oestrogen-related receptor (ERR)-1α-sterol regulatory element-binding protein 1 (SREBP1). Furthermore, resveratrol decreased the activity of phosphatidylinositol-3 kinase (PI3K)-Akt phosphorylation and class O forkhead box (FOXO)3a phosphorylation, which resulted in a decrease in B cell leukaemia/lymphoma 2 (BCL-2)-associated X protein (BAX) and increases in BCL-2, superoxide dismutase (SOD)1 and SOD2 production. Consequently, resveratrol reversed the increase in renal apoptotic cells and oxidative stress, as reflected by renal 8-hydroxy-deoxyguanosine (8-OH-dG), urinary 8-OH-dG and isoprostane concentrations. Resveratrol prevented high-glucose-induced oxidative stress and apoptosis in cultured mesangial cells through the phosphorylation of AMPK and activation of SIRT1-PGC-1α signalling and the downstream effectors, PPARα-ERR-1α-SREBP1.The results suggest that resveratrol prevents diabetic nephropathy in db/db mice by the phosphorylation of AMPK and activation of SIRT1-PGC-1α signalling, which appear to prevent lipotoxicity-related apoptosis and oxidative stress in the kidney.

Background Oxaliplatin, a platinum analogue, is an active drug in advanced anthracycline and taxane-pretreated breast cancer patients as a single agent and with 5-fluorouracil (5-FU) combination. TS-1 was developed by the scientific theory of both potentiating antitumor activity of 5-FU and reducing gastrointestinal toxicity. This trial was performed to evaluate the efficacy and safety of TS-1 in combination with oxaliplatin in metastatic breast cancer (MBC) patients previously treated with anthracycline and taxane chemotherapy. Methods: Between October 2007 and October 2009, MBC patients were enrolled in this prospective multicenter trial. Eligible criteria included age ≥18 years, at least one measurable lesion, prior treatment with anthracycline and taxane chemotherapy, and ECOG Performance Status 0–2. TS-1 40 mg/m2 b.i.d. on days 1–14 with oxaliplatin 130 mg/m2 on day 1 were administered every 3 weeks till disease progression. Primary end-point was response rate, and secondary end-points were time-to-progression (TTP), overall survival (OS), duration of response (DOR) and toxicities. Response was evaluated every 6 weeks according to the RECIST criteria v. 1.0 and toxicity was assessed with NCICTCAE v.3.0.(ClinicalTrials.gov identifier NCT00527930). Results: A total of 87 patients were enrolled. Median age was 48 years (range 30–71 years). Nineteen patients (21.8%) had de novo stage IV and 68 patients (78.2%) had recurrent disease. Thirty-five patients (40.2%) received two-lines of prior chemotherapy in palliative setting. Forty-eight patients (55.2%) had ≥ 3 disease sites. Fifty-four patients (62.1%) were hormone receptor positive, and 25 patients (28.7%) were triple negative. Five patients received prior anti-HER2 therapy. A total of 525 cycles were administered (median 6 cycles, range: 1 ∼ 22+ cycle). In per-protocol analysis, overall response rate was 38.5% (95% CI: 27.7−49.3) (CR 0%, PR 38.5%) and disease control rate (CR, PR, and SD) was 67.9% (95% CI: 57.5−78.3). Median TTP, OS, and DOR were 6.0 months (95% CI: 5.1−6.9 months), 19.4 months (95% CI: not estimated), 6.6 months (95% CI: 3.7−9.6 months), respectively. RR was not different by triple negativity (39.1% in TNBC vs. 38.2% in non-TNBC, P=0.361). TTP was not different according to the number of prior chemotherapy regimens. Reported grade 3 or 4 toxicities (per cycle) were neutropenia (10.3%), thrombocytopenia (5.5%), diarrhea (1.9%), vomiting (1.9%), and stomatitis (0.2%). There was no treatment-related death. Conclusions: SOX is an effective regimen in anthracycline and taxane pretreated MBC patients with manageable toxicities. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-16-06.

Background The objective of the study was to evaluate the implications of androgen receptor (AR) in breast cancers. Patients and methods We investigated immunohistochemical AR expression from the tissue microarrays of 931 patients between 1999 and 2005, and analyzed demographics and outcomes using uni-/multivariate analyses. Tumors with ≥10% nuclear-stained cells were considered positive for AR. Results AR was expressed in 58.1% of patients. AR was significantly related to older age at diagnosis, smaller size, well-differentiated tumors, higher positivity of hormone receptors, non-triple-negative breast cancers (non-TNBCs), and lower proliferative index. In estrogen receptor (ER)-negative tumors, AR was distinctively associated with human epidermal growth factor receptor type 2 (HER2) overexpression. With a mean follow-up of 72.7 months, AR was positively related to survival in ER-positive but not in ER-negative tumors. In Cox’s models, AR was an independent prognostic factor for disease-free survival in ER-positive cancers. Interestingly, molecular apocrine tumors (ER negative and AR positive) with HER2 positive status showed trends of poorer outcome, but AR had no impact on survival in patients with TNBC. Conclusions AR is significantly associated with favorable features in breast cancers and related to better outcomes in ER-positive not in ER-negative tumors. These results suggest that AR could be an additional marker for endocrine responsiveness in ER-positive cancers and a candidate for therapeutic targeting of ER-negative tumors.

SUMMARY Objective: Although the pathogenesis of aspirininduced urticaria (AIU) is not fully understood, mast cell activation has been noted in patients with AIU. Tumour necrosis factor (TNF)-a ,a potent pro-inflammatory cytokine, is released by human skin mast cells and other inflammatory cells in patients with urticaria. To investigate the role of TNF-a promoter polymorphisms in the development of AIU, we performed an association study of TNF-a promoter polymorphisms with AIU phenotype. Methods: Two hundred thirty-nine patients with AIU consisting of 120 patients with aspirin intolerant chronic urticaria (AICU) and 119 with aspirin-intolerant acute urticaria (AIAU), and 524 normal controls were enrolled. AIU was confirmed by oral aspirin challenge test. Five SNPs in the TNF-a gene (-1031T>C, -863C>A, -857C>T, -308G>A, -238G>A) were genotyped by a singlebase extension method. Haplotype analyses were done. Results: The genotype frequencies of TNF1031T>C and TNF-863C>A were significantly higher in the AIU patients than in the normal controlsinbothco-dominant(P =0 AE014,P =0 AE007) and dominant (P =0 AE007, P =0 AE004) models. The frequency of TNF-ht2[CACGG] containing a genotype in the AIU group was significantly higher in the normal controls with both co-dominant (P =0 AE004, Pc =0 AE02) and dominant models (P =0 AE002, Pc =0 AE01). Conclusions: These findings suggest that the two promoter polymorphisms of TNF-a at -1031T>C and -863C>A may contribute to the development of AIU.

Chronic urticaria/angioedema is a common phenotype in patients with aspirin sensitivity; however, its genetic mechanism is not understood. Transforming growth factor (TGF)beta1 is a key regulatory cytokine involved in allergic inflammation.We examined the association of a TGFbeta1 genetic polymorphism with aspirin-intolerant chronic urticaria (AICU) and aspirin-tolerant chronic urticaria (ATCU) in a Korean population.A promoter polymorphism in the TGFbeta1 gene, TGFbeta1 -509CT, was analysed in 112 AICU patients, 153 ATCU patients and 457 normal controls (NC), and the frequency was compared among the groups. Serum TGFbeta1 levels were measured by ELISA.The minor allele frequency of the -509CT polymorphism was significantly higher in patients with AICU compared with the other two groups (P0.02 for AICU vs. NC; P0.05 for AICU vs. ATCU). Among the AICU patients, those with the T allele tended to have lower serum TGFbeta1 levels.These findings suggest that the -509CT polymorphism in the TGFbeta1 promoter may contribute to the development of the AICU phenotype.

Objective: Visfatin, a novel adipokine, was revealed to be associated with obesity and to have insulin-mimetic effect. Eotaxin, which is an important chemokine in asthma, was recently reported to be associated with obesity in mice and humans. We evaluated the effect of exercise training on plasma visfatin and eotaxin levels in association with cardiovascular risk factors. Design: Forty-eight non-diabetic Korean women were evaluated before and after a 12 week exercise program including aerobic exercise (45 min/session, 300 Kcal/day) and muscle strength training (20 min/session, 100 Kcal/day) five times per week. Results: Plasma visfatin concentrations were elevated in obese subjects (body mass index, BMI≥25 kg/m2) when compared with non-obese subjects (16.4 ± 13.4 ng/ml vs 7.7 ± 5.2 ng/ml, P = 0.006), and eotaxin concentrations were elevated in subjects with central obesity (waist circumference, WC≥80 cm) when compared with those without central obesity (73.6 ± 17.8 pg/ml vs 64.2 ± 4.2 pg/ml, P = 0.005). In multiple regression analyses, visfatin levels were associated with BMI (R2 = 0.255) and eotaxin levels were associated with WC and body weight (R2 = 0.307). After the exercise program, body weight, blood pressure, fasting glucose, and insulin resistance of participants were decreased. Furthermore, plasma visfatin levels were significantly decreased from 13.6 ± 12.0 to 7.7 ± 7.9 ng/ml (P = 0.026) and eotaxin levels were reduced from 72.0 ± 16.7 to 66.9 ± 14.2 pg/ml (P = 0.018). Conclusions: Exercise training with weight loss induced a significant reduction of plasma visfatin and eotaxin levels in non-diabetic Korean women.

This study examined effects of calcium supplemented milk on bone loss in ovariectomized rats. Twenty four Sprague-Dawley female rats, 7 weeks-old, were divided into 4 groups, ovariectomized and fed diets containing: 1) control, no Ca supplemented milk, 2) ovx 1, Ca carbonate supplemented milk, 3) ovx 2, ionized Ca supplemented milk, and 4) ovx 3, nano Ca supplemented milk. All rats were fed 1 ml of milk containing 20 mg supplemented Ca. After 18 wk feeding, body weight gain and food efficiency ratio were significantly different between ovx 1 and ovx 3. Serum concentration of calcium and phosphorus were not different among groups. However, there was a significant difference in calcium content of dry femoral weight in ovx 3 compared with the control and ovx 2. In addition, femoral bone mineral density (g/cm 2 ) was significantly greater in ovx 3 than in other groups (p

The objectives of the present study were to initiate cloning of Korean native goat by somatic cell nuclear transfer (NT) and to examine whether unovulated (follicular) oocytes can support the same developmental ability of NT embryos as ovulated (oviductal) oocytes after hCG injection in stimulated cycles of the goat. The in vivo-matured and immature oocytes were collected from the oviducts and follicles of superovulated does, respectively, and the immature oocytes were maturated in vitro. Ear skin fibroblasts derived from a 3-yr-old female Korean native goat were used as the donors of nuclei or karyoplasts. Following fusion, activation and in vitro culture to a 2- to 4-cell stage, 49 in vitro-derived and 105 in vivo-derived embryos were transferred to 6 and 17 recipient does, respectively. One doe and three does of the respective groups were identified as pregnant by ultrasonography on day 30 after embryo transfer. However, only one doe, which had received in vivo-derived embryos, delivered a normal female kid of 1.9 kg on d 149. The cloned kid gained more weight than her age-matched females as much as 87% during the first 4 mo after birth (17.7 vs. 9.4±0.8 kg) and reached puberty at 6-mo age a few months earlier than normal female does. The telomere length of the kid, which was similar to that of the donor fibroblast at 2-mo age, decreased 8% between 2- and 7-mo ages. Moreover, at 7-mo age, she had 21% shorter telomere than her age-matched goats. To our knowledge, this is the first case in which a cloned animal born with a normal weight exhibited accelerated growth and development. The unusually rapid growth and development of the cloned goat may have resulted from SCNT-associated epigenetic reprogramming involving ielomere shortening.

We report two cases of deep tracheal laceration in female patients after balloon dilation for benign tracheobronchial stenosis. Immediate post-procedure bronchoscopy and CT including 3D reconstructions showed deep lacerations in the posterior tracheal wall. Clinically, the patients' dyspnoea subsided and there has been no recurrence during follow-up after balloon dilation. On the follow-up 3D-reconstructed CT scans obtained 2 months and 8 months following balloon dilation, respectively, the lacerations had healed completely and there was considerable improvement in lumen size.

Autocrine stimulation via coexpression of hepatocyte growth factor (HGF) and its receptor (Met) has been reported in many human sarcomas, but few in carcinomas. In this report, we found that one gastric cancer cell line, SNU-484, among 11 gastric cell lines tested has an autocrine HGF- Met stimulation. RT-PCR, ELISA and scattering assay using MDCK cells revealed that SNU-484 cells secreted a significant amount of active HGF (about 1.25 +/- 0.41 ng/24 h/10(6) cells) into conditioned medium. Resultantly, Met in this cell line was constitutively phosphorylated. Neutralizing antibodies against HGF reduced the tyrosine phosphorylation of Met, resulting in the inhibition of cell proliferation and migration (P

To develop a novel gene therapeutic modality for the effective treatment of benign prostatic hyperplasia (BPH), we investigated the properties of toxic gene therapy utilizing prostate-specific antigen (PSA) promoter driving herpes simplex virus thymidine kinase (HSV-TK) suicide gene to induce highly selective molecular ablation of epithelial cells with minimal systemic toxicity in canine prostate. Replication-defective recombinant adenoviral vectors containing HSV-TK gene under transcriptional control of long PSA promoter (Ad-PSA-HSV-TK) were developed and delivered in an situ manner. Briefly, laparotomies were performed and Ad-PSA-HSV-TK (1 x 10(9) PFUs) was injected into the left lateral lobe of prostate only on days 1 and 7 with appropriate prodrug acyclovir in adult Beagle dogs. The therapeutic efficacy was evaluated on the 56th experimental day. The striking apoptosis of epithelial cells was identified in the treated left half of canine prostate on TUNEL assay. On immunohistochemical studies, there was markedly decreased number of PSA-secreting epithelial cells compared to control. Also significant atrophy of prostate glands, associated with dense infiltration of lymphocytes and plasma cells, was identified in the treated side. The PSA promoter-based suicide gene therapy induced highly selective and definite ablation of epithelial cells in benign canine prostate. Our novel approach could open opportunity of gene therapeutic modality for the treatment of clinical BPH.

Summary When considering brachial plexus block as a practical alternative to general anaesthesia for upper limb surgery, the time to achieve complete sensory block is a clinically important variable. In this prospective randomised double-blind controlled trial, we investigated the hypothesis that addition of hyaluronidase to ropivacaine may reduce the time to achieve complete sensory block after axillary brachial plexus block. The patients were randomly assigned into a hyaluronidase group (n = 24) and a control group (n = 24). The hyaluronidase group received ropivacaine 0.5% with 100 IU.ml−1 of hyaluronidase, and the control group received ropivacaine alone. The primary endpoint was the time to achieve complete sensory block. The hyaluronidase group demonstrated significantly shorter mean (SD) sensory block onset time (13.8 (6.0) min) compared with the control group (22.5 (6.3) min, p

Recent studies suggest that the interaction between small intestinal nutrient stimulation and the blood glucose concentration is important in the regulation of gastric motility and appetite. The purpose of this study was to determine whether the effects of cholecystokinin octapeptide (CCK-8) on antropyloric motility and appetite are influenced by changes in the blood glucose concentration within the normal postprandial range. Seven healthy volunteers were studied on 4 separate days. A catheter incorporating a sleeve sensor was positioned across the pylorus, and the blood glucose was stabilized at either 4 mmol/l (2 days) or 8 mmol/l (2 days). After the desired blood glucose had been maintained for 90 min, an intravenous infusion of either CCK-8 (2 ng ⋅ kg− 1 ⋅ min− 1) or saline (control) was given for 60 min. Thirty minutes after the infusion began, the catheter was removed and subjects drank 400 ml of water with guar gum before being offered a buffet meal. The amount of food consumed (kcal) was quantified. The order of the studies was randomized and single-blinded. There were fewer antral waves at a blood glucose of 8 than at 4 mmol/l during the 90-min period before the infusions ( P < 0.05) and during the first 30 min of CCK-8 or saline infusion ( P = 0.07). CCK-8 suppressed antral waves ( P < 0.05), stimulated isolated pyloric pressure waves (IPPWs) ( P < 0.01), and increased basal pyloric pressure ( P < 0.005) compared with control. During administration of CCK-8, basal pyloric pressure ( P < 0.01), but not the number of IPPWs, was greater at a blood glucose of 8 mmol/l than at 4 mmol/l. CCK-8 suppressed the energy intake at the buffet meal ( P < 0.01), with no significant difference between the two blood glucose concentrations. We conclude that the acute effect of exogenous CCK-8 on basal pyloric pressure, but not appetite, is modulated by physiological changes in the blood glucose concentration.

In order to determine the operating condition of an uranium chlorination process with U3O8-C-Cl2 system, the experimental conditions have been evaluated preliminarily by the thermochemical analysis and experimentally confirmed in this study. The dry-type chlorination of U3O8 occurs as irreversible and exothermic reaction and produces many kinds of chloride compounds such as UCl3, UCl4, UCl5 and UCl6 in the air and humidity controlled argon environment. Taking account of Gibbs free energy and vapor pressure for various chloride compounds, the proper temperature range of chlorination appears to be 863 to 953 K in aspects of increasing reaction rate and the yield of nonvolatile product. In the course of the experimental confirmation the powder of U3O8 is perfectly converted into uranium chlorides within 4 hours above 863K, and then the maximum fraction of uranium chloride remaining in the reactor is about 30% of total conversion mass.

The plasma and peripheral blood mononuclear cell (PBMC) titer of feline immunodeficiency virus (FIV) in experimentally infected cats was assessed following administration of either zidovudine or cyclosporine. Treatments were begun 24 h post infection (p.i.) and continued for 4 weeks. Zidovudine treatment did not prevent establishment of infection with FIV, but plasma virus titers were significantly lower than controls at 2 weeks p.i. This reduction of plasma virus titer by zidovudine was not maintained at subsequent sampling times. Similarly, cyclosporine treatment initially lowered plasma virus titers at 2 weeks p.i., but at 4 weeks p.i. the plasma virus titers in cyclosporine-treated cats were significantly higher than in the untreated group. In the untreated group, plasma virus titers declined rapidly to an undetectable level by 14 weeks p.i. Neither zidovudine or cyclosporine treatment significantly influenced the titer of FIV in PBMCs. In all groups (untreated, zidovudine and cyclosporine) the titers in PBMC were high for the duration of the experiment. The decline in plasma virus titers in immunocompetent cats combined with the effect of cyclosporine on plasma titers strongly suggests that the immune system plays a major role in clearing FIV from plasma. In contrast, it appears that the immune response has little impact on PBMC virus titers. This shows that for complete assessment of antiviral agents, both cell-free and cell-associated virus titers must be examined. We also suggest that the limitation of viral titers in PBMC may be of critical importance in the control of lentiviral infection.

Background The danger hypothesis provides a new perspective of the mechanisms underlying drug allergy. In this study, we evaluated associations between variations in the genes involved in danger signal pathways and antibiotic-induced cutaneous allergic reactions (AICARs). Methods Two hundred cases with urticaria, angio-oedema, maculopapular rash, and erythema multiforme caused by antibiotics were extracted from the database of the Adverse Drug Reaction Research Group in Korea. All cases were confirmed by an allergy specialist. Causative antibiotics included penicillin, cephalosporin, quinolone, and others (approximately 40 different types). Ten single nucleotide polymorphisms (SNPs) in seven genes (-318C > T, +49A > G, and +6230G > A in CTLA4, IVS+ 17T > C in CD28, -3479T > G and I170V in CD86, -1 C > T in CD40, -3458A > G in CD40LG, -308G > A in TNF, and - 31T > C in IL1B) were scored for cases and for healthy subjects without a history of AICARs. Results Our analysis failed to reveal differences in the distribution of the 10 SNPs between cases and controls. However, we could find a gene-gene interaction between — 1C > T in CD40 and -3458A > G in CD40L using multifactor dimensionality reduction analysis. Subjects with minor alleles of both SNPs showed a significant risk for developing AICARs [P= 0.017, odds ratio (OR) (95% confidence interval) = 2.93 (1.20-7.97)]. Conclusion Our findings suggest that a genetic interaction between CD40 and CD40L favours the development of AICARs.

Summary Objectives: We investigated the association between metabolic syndrome (MS) and health-related quality of life (HRQOL) assessed using generalised and obesity-specific QOL instruments. Methods: We recruited 456 outpatients [age: 19–81 years, body mass index (BMI): 16.3–36.7 kg/m2] in the primary care division from 12 general hospitals in Korea. HRQOL was measured using EuroQol comprising the health states descriptive system (EQ-5D) and visual analogue scale (EQ-VAS) as a general instrument. The Korean Obesity-related QOL scale (KOQOL) composed of six domains was used as a disease-specific QOL instrument. MS was defined on the basis of International Diabetes Federation (IDF) criteria with Korean-specific waist circumference cutoffs (men: 90 cm, women: 85 cm). Results: Subjects with MS displayed significantly higher impairment of EQ-5D and KOQOL. Binary logistic regression analysis of MS patients with controls for age, gender, smoking, alcohol, exercise, education, income, marital status and medication history disclosed odds ratio (OR) values of 2.13 (1.33–3.41) for impaired total KOQOL, 2.07 (1.31–3.27) for impaired physical health, 1.63 (1.03–2.60) for impaired work-related health, 2.42 (1.45–4.04) for impaired routine life, 2.08 (1.27–3.40) for impaired sexual life and 2.56 (1.59–4.11) for diet distress. Among the EQ-5D dimensions, only pain/discomfort displayed a significantly increased OR of 1.60 (1.01–2.56) in MS group. Conclusions: Subjects with MS displayed a significantly impaired HRQOL compared with those without MS. MS and HRQOL were more strongly associated in obesity-specific QOL than in generalised QOL.

Summary To evaluate the significance of specific IgG and specific IgG4 in the development of work-related respiratory symptoms, specific IgG and specific IgG4 to Black GR-human serum albumin (HSA) conjugate were measured by ELISA in 309 dye-exposed workers and 63 unexposed patients as negative controls. A survey revealed that 78 (25.2%) had work-related lower respiratory symptoms with or without nasal, skin or eye symptoms. Specific IgG and specific IgG4 were detected in 23% and 14% of the exposed workers, respectively. The prevalence of specific IgG and specific IgG4 was significantly higher in smokers and workers with specific IgE or those with lower respiratory symptoms (P < 0.05), but was not associated with work station, duration of dye exposure or atopy. These results suggested that the existence of specific IgG to Black GR HSA might represent a response to Black GR exposure and be closely related with work-related respiratory symptoms.

Aspirin-intolerant asthma (AIA) refers to the development of bronchoconstriction in asthmatic individuals following the ingestion of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs). Angiotensin I-converting enzyme (ACE), a membrane-bound peptidase present in the lung, plays a pivotal role in the metabolism of the endogenous peptides involved in the pathogenesis of asthma.We screened a Korean asthma cohort (581 asthmatics including 81 aspirin-intolerant asthmatics and 231 aspirin-tolerant asthmatics, and 181 normal controls) for four single nucleotide polymorphisms (SNPs; -262 AT and -115 TC in the 5'-flanking region and +5467 TC [Pro450Pro] and+11860 AG [Thr776Thr] in the coding region) and one ins/del (+21288 CT) in the ACE gene.None of the SNPs or haplotypes showed any association with the development of asthma, but they were significantly associated with the risk of AIA. Logistic regression indicated that the frequency of the rare alleles of -262 AT and -115 TC was higher in subjects with AIA than in subjects with aspirin-tolerant asthma (ATA) (P=0.003-0.01, P( corr)=0.015-0.05). Subjects homozygous for the rare alleles of -262 AT and -115 TC showed a greater decline in forced expiratory volume in 1 s (FEV(1)) after aspirin provocation than those homozygous for the common alleles (P0.05). A luciferase reporter assay indicated that ACE promoters containing the rare -262 AT allele possessed lower activity than did those containing the common allele (P=0.009). In addition, ACE promoters bearing the rare -115 TC allele had no luciferase activity. DNA-protein binding assays revealed a band containing the ACE promoter region (including -262 A) and a protein complex.The -262 AT polymorphism in the promoter of the ACE gene is associated with AIA, and the rare allele of -262 AT may confer aspirin hypersensitivity via the down-regulation of ACE expression.

We compare test characteristics of abdominal computed tomography (CT) with and without oral contrast for identifying intra-abdominal injuries.This was a planned subanalysis of a prospective, multicenter study of children (18 years) with blunt torso trauma. Children imaged in the emergency department with abdominal CT using intravenous contrast were eligible. Oral contrast use was based on the participating centers' guidelines and discretions. Clinical courses were followed to identify patients with intra-abdominal injuries. Abdominal CTs were considered positive for intra-abdominal injury if a specific intra-abdominal injury was identified and considered abnormal if any findings suggestive of intra-abdominal injury were identified on the CT.A total of 12,044 patients were enrolled, with 5,276 undergoing abdominal CT with intravenous contrast. Of the 4,987 CTs (95%) with documented use or nonuse of oral contrast, 1,010 (20%) were with and 3,977 (80%) were without oral contrast; 686 patients (14%) had intra-abdominal injuries, including 127 CTs (19%) with and 559 (81%) without oral contrast. The sensitivity in the detection of any intra-abdominal injury in the oral contrast versus no oral contrast groups was sensitivitycontrast 99.2% (95% confidence interval [CI] 95.7% to 100.0%) versus sensitivityno contrast 97.7% (95% CI 96.1% to 98.8%), difference 1.5% (95% CI -0.4% to 3.5%). The specificity of the oral contrast versus no oral contrast groups was specificitycontrast 84.7% (95% CI 82.2% to 87.0%) versus specificityno contrast 80.8% (95% CI 79.4% to 82.1%), difference 4.0% (95% CI 1.3% to 6.7%).Oral contrast is still used in a substantial portion of children undergoing abdominal CT after blunt torso trauma. With the exception of a slightly better specificity, test characteristics for detecting intra-abdominal injury were similar between CT with and without oral contrast.

Complete eversion and prolapse of the urinary bladder is extremely rare. To the best of our knowledge, the imaging findings of complete bladder eversion have not been documented in the literature. Here, we report a case of complete eversion and prolapse of the urinary bladder demonstrated on MRI. Concurrent primary adenocarcinoma was found in the thickened wall of the everted urinary bladder.

Summary Background Urticaria/angioedema is a common aspirin-induced allergy; however, its pathogenic mechanism is not understood. Objective In order to uncover the genetic mechanism, we studied the associations of the human leucocyte antigen (HLA) genotypes in patients with aspirin-induced urticaria compared with aspirinintolerant asthma and normal control in a Korean population. Methods Ninety-four aspirin-induced urticaria patients presenting urticaria/angioedema-induced by both ASA and NSAID (50 had underlying chronic urticaria) and showing positive responses on oral aspirin challenge test, 76 aspirin-intolerant asthmatics with positive responses on lysine–aspirin bronchoprovocation test, and 185 normal healthy controls were enrolled. HLA-DRB1, DQB1, and DPB1 genotypings were performed by direct DNA sequencing analysis. Results The allele frequencies of HLA-DRB1*1302 (18.1%) and HLA-DQB1*0609 (10.1%) in aspirin-induced urticaria were significantly higher than in aspirin-intolerant asthma (5.3%, P 5 0.0004; 2.0%, P 5 0.0024) and in normal controls (8.1%, P 5 0.0005; 3.2%, P 5 0.0008), and they remained significant after correcting for multiple comparisons. The patients with these two HLA markers had a significantly younger age than patients without, while no associations were found in with respect to atopic status, a history of previous allergic diseases, total IgE level, or presence of underlying chronic urticaria (P40.05, respectively). In haplotype analysis, the HLA-DRB1*1302DQB1*0609-DPB1*0201 was significantly higher in the aspirin-induced urticaria (8.0%) than in the aspirin-intolerant asthma (0.7%, P 5 0.0014) and normal controls (2.0%, P 5 0.0006). Conclusion These findings suggest that the HLA-DRB1*1302-DQB1*0609-DPB1*0201 may be a strong genetic marker to determine the aspirin-induced urticaria phenotype.

Aims To evaluate the effect of weight reduction on parameters of the metabolic syndrome in obese patients according to their pattern of abdominal fat distribution. Methods A longitudinal intervention study, consisting of a 12-week weight reduction programme, including lifestyle modification and adjuvant appetite suppressant, in 38 subjects with visceral obesity and 47 subjects with subcutaneous obesity. Visceral, subcutaneous and total adipose tissue areas were determined by CT scan at the level of L4–L5. Parameters for components of the metabolic syndrome were measured before and after weight reduction. Results Reductions in body weight, BMI and subcutaneous adipose tissue area were greater in the subcutaneous than in the visceral obesity group. In contrast, changes in fasting plasma glucose, insulin, and HOMA score were higher in the visceral than in the subcutaneous obesity group. Changes in visceral adipose tissue area were significantly related to changes in fasting plasma glucose, triglycerides and HOMA score. Conclusions Visceral fat reduction induced greater beneficial effects on parameters of the metabolic syndrome than subcutaneous fat reduction. Evaluation of changes in abdominal fat distribution is necessary when obese subjects enter a weight reduction programme.

Summary 1 We measured the plasma glucose and the glycosylated haemoglobin at the time of sacrifice in streptozotocin-induced diabetic mellitus (DM) rats. 2 In diabetic rats, plasma glucose and glycosylated haemoglobin was increased as compared with normal rats, and vitamin E inhibited the increase of glycosylated haemoglobin level but vitamin C had no effect. 3 The peroxidized proteins and lipids from the diabetic organs such as liver or kidney were measured to assess the oxidative damage. The 2,4-dinitrophenyl-hydrazine (DNPH) incorporation method was used to measure the peroxidized protein. In diabetic rats, DNPH incorporation was increased as compared with normal rats and vitamin E also inhibited the increase of DNPH incorporation but vitamin C had no effect. It suggests that the protein oxidation occurred on the liver in diabetic rats and the oxidative stress is general in the diabetic condition. 4 We measured the systolic arterial pressure and mean arterial pressure in normal rats, nephrectomy (NEPH)-rats, diabetic rats (DM), and NEPH-diabetic rats (NEPH-DM). Blood pressure was significantly increased in DM and NEPH-DM as compared with normal rats. 5 In conclusion, plasma glucose, glycosylated haemoglobin, and the oxidation of proteins or lipid were increased in diabetic rats. Vitamin E decreased the plasma glucose, glycosylated haemoglobin and the oxidation of proteins and lipid, but vitamin C had no effects.

Inflammatory orbital pseudotumor is a benign space-occupying lesion of unknown origin that involves all or part of the fatty tissue within the orbit. Occasionally the disease may extend into the middle cranial, the pterygopalatine, and the infratemporal fossa through the various foramina of the orbit, although extension into the infratemporal fossa is very rare. We present a case which extends into the infratemporal fossa through the inferior orbital fissure, resulting in presenting symptoms mimicking temporomandibular joint dysfunction.

This study evaluated a modified plastic straw method for vitrification of in vitro-produced (IVP) bovine blastocysts. A modified straw was used that has a depressed area on its inner surface to which embryos attach. The IVP blastocysts were randomly assigned into 3 groups: (1) attachment of embryos to the inner surface of a plastic straw (aV), (2) attachment of embryos to the inner surface of a modified plastic straw (maV), and (3) non-vitrified (control). The recovery rates of blastocysts were not significantly different between the aV and maV groups (95.8 v. 94.3%; P > 0.05). The survival of post-thaw blastocysts did not significantly differ between the aV and maV groups (86.4 v. 88.2%; P > 0.05). The total cell number of blastocysts was significantly higher in the control group than in the aV and maV groups (142 ± 21.8 v. 117 ± 29.7 and 120 ± 25.2; P