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  • 1
    Language: English
    In: International Urogynecology Journal, 2014, Vol.25(9), pp.1179-1184
    Description: Byline: Linda Brubaker (1), Charles W. Nager (2), Holly E. Richter (3), Anthony Visco (4), Ingrid Nygaard (5), Matthew D. Barber (6), Joseph Schaffer (7), Susan Meikle (8), Dennis Wallace (9), Noriko Shibata (10), Alan J. Wolfe (10) Keywords: Microbiome; Urinary bacteria; Urinary urgency incontinence; Urinary tract infection Abstract: Introduction and hypothesis This study's aims were to detect and quantify bacterial DNA in the urine of randomized trial participants about to undergo treatment for urinary urgency incontinence (UUI) without clinical evidence of urinary tract infection (UTI) and to determine if the presence of bacterial DNA in baseline urine relates to either baseline urinary symptoms or UTI risk after urinary tract instrumentation. Methods Women without clinical evidence of baseline UTI were randomized to cystoscopic onabotulinum toxin A injection and oral placebo medication versus cystoscopic placebo injection and active oral medication. Bacterial DNA in participants' catheterized urine was measured by quantitative polymerase chain reaction (qPCR). Results Bacterial DNA was detected in the urine of 38.7 % of participants (60 out of 155). In these 60 qPCR-positive participants, baseline daily UUI episodes were greater than in the 95 qPCR-negative participants (5.71 [[+ or -]2.60] vs 4.72 [[+ or -]2.86], p=0.004). Neither symptom severity by questionnaire nor treatment outcome was associated with qPCR status or with qPCR level in qPCR-positive subjects. In contrast, the presence of urinary bacterial DNA was associated with UTI risk: only 10 % of the qPCR-positive women developed a UTI post-treatment, while 24 % of the qPCR-negative women did so. The median qPCR level for qPCR-positive samples did not differ significantly by UTI status (UTI 2.58x10.sup.5 vs no UTI 1.35x10.sup.5 copies/mL, p=0.6). Conclusions These results may indicate a urinary bacterial contribution to both baseline UUI and the risk of post-treatment UTI. Author Affiliation: (1) Departments of Obstetrics and Gynecology and Urology, Stritch School of Medicine, Loyola University Chicago, 2160 S. First Avenue, Boulevard 120, Room 420, Maywood, IL, 60153, USA (2) Department of Reproductive Medicine, UC San Diego Health System, San Diego, San Diego, CA, USA (3) Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, AL, USA (4) Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA (5) Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, UT, USA (6) Obstetrics, Gynecology and Women's Health Institute, Cleveland Clinic, Cleveland, OH, USA (7) Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX, USA (8) Gynecologic Health and Disease Branch, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA (9) Health Sciences Division, Research Triangle Institute, Research Triangle Park, NC, USA (10) Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA Article History: Registration Date: 29/12/2013 Received Date: 10/10/2013 Accepted Date: 28/12/2013 Online Date: 11/02/2014 Article note: The ABC trial is registered at www.clinicaltrials.gov as NCT01166438.
    Keywords: Microbiome ; Urinary bacteria ; Urinary urgency incontinence ; Urinary tract infection
    ISSN: 0937-3462
    E-ISSN: 1433-3023
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  • 2
    Language: Japanese
    In: Rinsho byori. The Japanese journal of clinical pathology, February 2008, Vol.56(2), pp.95-100
    Description: Quantitative measurement of hepatitis C virus (HCV) has been performed by PCR method. However, PCR method has problems such as a special instrument, a complicated manual skill and a high cost. Recently, simple and highly sensitive HCV core antigen (Ag) method has been developed. We performed fundamental evaluation of HCV core Ag method, and compared HCV core Ag method with HCV PCR high-range method. The intra-assay and inter-assay variation coefficients for HCV core Ag were calculated to be within the ranges of 1.0-11.3% and 0.8-9.3%, respectively. The test of dilution linearity revealed the unstableness in the vicinity of a cut-off level of 50 fmol/L. Based on the result of the high-range method; sensitivity, specificity, positive predictive value, negative predictive value, and agreement rate were 97.0%, 100%, 100%, 82.0%, and 96.5%, respectively. The correlation between the HCV core Ag method and the high-range method was r = 0.87. Cost per sample and time from sample preparation to final report for HCV core Ag were cheaper and shorter than those of HCV PCR method, respectively. We consider that the HCV core Ag method seems to be useful as the quantitative measurement of HCV with respect to rapidness, easiness and low cost.
    Keywords: Hepatitis C Antigens -- Analysis ; Nucleic Acid Amplification Techniques -- Methods ; Viral Core Proteins -- Analysis
    ISSN: 0047-1860
    Source: MEDLINE/PubMed (U.S. National Library of Medicine)
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  • 3
    Language: English
    In: PLoS ONE, 01 January 2017, Vol.12(5), p.e0178123
    Description: Sarcopenia is an aging and disease-related syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength, with the risk of frailty and poor quality of life. Sarcopenia is diagnosed by a decrease in skeletal muscle index (SMI) and reduction of either handgrip strength or gait speed. However, measurement of SMI is difficult for general physicians because it requires special equipment for bioelectrical impedance assay or dual-energy X-ray absorptiometry. The purpose of this study was, therefore, to explore a novel, simple diagnostic method of sarcopenia evaluation in patients with cardiovascular diseases (CVD).We retrospectively investigated 132 inpatients with CVD (age: 72±12 years, age range: 27-93 years, males: 61%) Binomial logistic regression and correlation analyses were used to assess the associations of sarcopenia with simple physical data and biomarkers, including muscle-related inflammation makers and nutritional markers.Sarcopenia was present in 29.5% of the study population. Serum concentrations of adiponectin and sialic acid were significantly higher in sarcopenic than non-sarcopenic CVD patients. Stepwise multivariate binomial logistic regression analysis revealed that adiponectin, sialic acid, sex, age, and body mass index were independent factors for sarcopenia detection. Sarcopenia index, obtained from the diagnostic regression formula for sarcopenia detection including the five independent factors, indicated a high accuracy in ROC curve analysis (sensitivity 94.9%, specificity 69.9%) and the cutoff value for sarcopenia detection was -1.6134. Sarcopenia index had a significant correlation with the conventional diagnostic parameters of sarcopenia.Our new sarcopenia index using simple parameters would be useful for diagnosing sarcopenia in CVD patients.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 4
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 28 May 2002, Vol.99(11), pp.7367-72
    Description: Prostaglandin D(2) (PGD(2)), a major cyclooxygenase product in a variety of tissues and cells, readily undergoes dehydration to yield the bioactive cyclopentenone-type PGs of the J(2)-series, such as 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)). The observation that the level of 15d-PGJ(2) increased in the tissue cells from patients with sporadic amyotrophic lateral sclerosis suggested that the formation of 15d-PGJ(2) may be closely associated with neuronal cell death during chronic inflammatory processes. In vitro experiments using SH-SY5Y human neuroblastoma cells revealed that 15d-PGJ(2) induced apoptotic cell death. An oligonucleotide microarray analysis demonstrated that, in addition to the heat shock-responsive and redox-responsive genes, the p53-responsive genes, such as gadd45, cyclin G1, and cathepsin D, were significantly up-regulated in the cells treated with 15d-PGJ(2). Indeed, the 15d-PGJ(2) induced accumulation and phosphorylation of p53, which was accompanied by a preferential redistribution of the p53 protein in the nuclei of the cells and by a time-dependent increase in p53 DNA binding activity, suggesting that p53 accumulated in response to the treatment with 15d-PGJ(2) was functional. The 15d-PGJ(2)-induced accumulation of p53 resulted in the activation of a death-inducing caspase cascade mediated by Fas and the Fas ligand.
    Keywords: Apoptosis -- Drug Effects ; Immunologic Factors -- Pharmacology ; Neurons -- Physiology ; Prostaglandin D2 -- Analogs & Derivatives
    ISSN: 0027-8424
    E-ISSN: 10916490
    Source: MEDLINE/PubMed (U.S. National Library of Medicine)
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  • 5
    In: The New England Journal of Medicine, 2017, Vol.376(11), pp.1038-1046
    Description: We assessed the feasibility of transplanting a sheet of retinal pigment epithelial (RPE) cells differentiated from induced pluripotent stem cells (iPSCs) in a patient with neovascular age-related macular degeneration. The iPSCs were generated from skin fibroblasts obtained from two patients with advanced neovascular age-related macular degeneration and were differentiated into RPE cells. The RPE cells and the iPSCs from which they were derived were subject to extensive testing. A surgery that included the removal of the neovascular membrane and transplantation of the autologous iPSC-derived RPE cell sheet under the retina was performed in one of the patients. At 1 year after surgery, the transplanted sheet remained intact, best corrected visual acuity had not improved or worsened, and cystoid macular edema was present. (Funded by Highway Program for Realization of Regenerative Medicine and others; University Hospital Medical Information Network Clinical Trials Registry [UMIN-CTR] number, UMIN000011929 .) A goal of regenerative medicine is to use induced pluripotent stem cells to generate an autologous graft for transplantation. This study tests the feasibility of the approach to treat age-related macular degeneration. Age-related macular degeneration (AMD) is one of the most prevalent retinal diseases that threaten vision in older populations in developed countries. 1 – 4 Neovascular (also called “wet”) AMD is more prevalent than atrophic (or “dry”) AMD in Japan 5 and is associated with the ectopic development of a choroidal neovascular membrane in the subretinal space of the center of the retina (the macula). Physical disruption and functional impairment of the retinal pigment epithelium (RPE), a monolayer sheet of cells that supports the overlying photoreceptors and underlying choroidal vasculature, occur in the course of wet AMD. 6 Current treatments of AMD that involve the . . .
    Keywords: Induced Pluripotent Stem Cells -- Cytology ; Macular Degeneration -- Therapy ; Retinal Pigment Epithelium -- Cytology;
    ISSN: 0028-4793
    E-ISSN: 1533-4406
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  • 6
    Language: English
    In: Atherosclerosis, December 2013, Vol.231(2), pp.365-370
    Description: Intima-media thickness (IMT) of the carotid artery, flow-mediated dilation (FMD) of the brachial artery, and pulse wave velocity of the central artery (PWV) have been widely used to evaluate progression of atherosclerosis. Our previous work has revealed that IMT, FMD and PWV are related to each other, and the combination of these measurements was useful in identifying patients with atherosclerotic disease. The aim of the present study was to investigate whether combination of these measurements would predict future cardiovascular events better than each test alone. From November 2000 to March 2008, 274 consecutive elderly subjects (men/women; 114/160, mean age; 71 ± 12 years) were enrolled in this study. We measured IMT, FMD, and PWV in all of these subjects and followed them for a mean of 41 ± 28 months. During the follow-up period, vascular events occurred in 42 patients (15.3%). IMT (hazard ratio = 1.28 [95%CI, 1.09–1.50],  = 0.002 per 0.1 mm increase in mean IMT) and brachial-ankle (ba) PWV (hazard ratio = 1.06 [95%CI, 1.01–1.10],  = 0.015 per 1 m/s increase in baPWV) were independent predictors of future vascular events by Cox proportional hazard analysis, although FMD did not reach statistical significance (hazard ratio = 0.85 [95%CI, 0.72–1.01],  = 0.062 per 1% increase in %FMD). Importantly, the number of tests showing results in the worst tertile was a more powerful predictor (hazard ratio = 2.21 [95%CI, 1.42–3.43],  = 0.0004 for number of tests showing worst tertile) of future vascular events than either IMT, baPWV, or FMD alone. When both IMT and baPWV (with respective cut-off values of 0.98 mm and 19.1 m/s) were taken into consideration, the efficacy increased as compared with each test alone (odds ratio 4.9). These results indicate that IMT and baPWV, especially when combined, are useful in predicting future vascular events in elderly subjects.
    Keywords: Intima-Media Thickness ; Flow-Mediated Dilation ; Pulse Wave Velocity ; Vascular Event ; Medicine
    ISSN: 0021-9150
    E-ISSN: 1879-1484
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  • 7
    Language: English
    In: Japanese journal of clinical oncology, 01 August 2018, Vol.48(8), pp.777-780
    Description: A randomized phase III trial comparing watchful waiting with first-line rituximab for advanced stage follicular lymphoma commenced in Japan in December 2016. Watchful waiting is the current standard treatment for stages III and IV (Ann Arbor classification) follicular lymphoma with low tumour burden. This study aimed to confirm the superiority of early administration of first-line rituximab in terms of event-free survival to watchful waiting for stages III and IV follicular lymphoma with low tumour burden. A total of 290 patients will be accrued from 50 Japanese institutions within 5 years. The primary endpoint is event-free survival defined as the period from registration to diagnosis of high tumour burden, therapy using cytotoxic chemotherapy and/or radiotherapy, or death. The secondary endpoints are overall survival, progression-free survival, cytotoxic chemotherapy/radiotherapy-free survival, histological transformation-free survival, response rate, adverse events and serious adverse events. This trial has been registered at the UMIN Clinical Trials Registry as UMIN000025187 (http://www.umin.ac.jp/ctr/index.htm).
    Keywords: Tumor Burden ; Watchful Waiting ; Lymphoma, Follicular -- Drug Therapy ; Rituximab -- Therapeutic Use
    ISSN: 03682811
    E-ISSN: 1465-3621
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  • 8
    Language: Japanese
    In: No shinkei geka. Neurological surgery, April 2016, Vol.44(4), pp.283-93
    Description: It has been pointed out that the motor evoked potential(MEP)with a subdural electrode is useful in the intraoperative monitoring for unruptured aneurysm surgery. However, in some cases, we experienced postoperative ischemic complications despite evaluating the motor function via MEP monitoring. Herein, we have reported the usefulness and problems of intraoperative monitoring with MEP to evaluate brain dysfunction caused by insufficiency of cerebral blood flow. Out of 279 aneurysm surgery procedures, we performed MEP monitoring in 142 cases and successfully recorded in 126 cases. We compared the ischemic complication rate of the group for which MEP was monitored with that of the group for which MEP was not monitored. The whole ischemic complication rate was decreased in the group that underwent MEP monitoring. Thus, it was suggested that MEP monitoring was useful for avoiding ischemic complications. In internal carotid artery aneurysms, the amplitude of MEP changed and recovered in 2 cases and disappeared in one case. In anterior cerebral artery aneurysms, the amplitude of MEP changed and recovered in 2 cases. In middle cerebral artery aneurysms, the amplitude of MEP changed and recovered in 5 cases. We could avoid ischemic complications by intraoperative MEP monitoring in many cases. However, in some cases, we found ischemic complications that were not detected by MEP monitoring with a subdural electrode. In these cases, transcranial stimulation in combination with subdural electrode might be effective in avoiding ischemic complications that might occur after dural closure.
    Keywords: Evoked Potentials, Motor ; Intracranial Aneurysm -- Physiopathology
    ISSN: 0301-2603
    E-ISSN: 18821251
    Source: MEDLINE/PubMed (U.S. National Library of Medicine)
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  • 9
    Language: English
    In: Journal of Pharmacological Sciences, 2012, Vol.119(4), pp.324-329
    Description: The effect of renal impairment on the pharmacokinetics of a single oral dose of memantine (10 mg) was determined in Japanese subjects. Subjects were assigned to four groups based on baseline creatinine clearance (CL ): normal renal function (〉 80 mL/min, n = 6), and mild (50 to ≤ 80 mL/min, n = 6), moderate (30 to 〈 50 mL/min, n = 6), and severe renal impairment (5 to 〈 30 mL/min, n = 7). Mean memantine maximum plasma concentration (C ) was similar in the groups (12.66, 17.25, 15.75, and 15.83 ng/mL, respectively), as was mean time to C (6.2, 5.2, 4.3, and 5.4 h, respectively). However, exposure to memantine determined from mean area under the plasma concentration–time curve was 1.62-, 1.97-, and 2.33-times higher in subjects with mild, moderate, and severe renal impairment, respectively, as compared to controls with normal renal function. Mean memantine plasma elimination half-life increased according to increasing renal impairment (61.15, 83.00, 100.13, and 124.31 h, respectively), while mean cumulative urinary recovery of unchanged memantine in 72 h after dosing decreased according to increasing renal impairment (33.68%, 33.47%, 23.60%, and 16.17%, respectively). These results are the same as those in the previous study on caucasian individuals, when compared per body weight. It is suggested that the dose of memantine should be halved in patients with renal impairment.
    Keywords: Memantine ; Renal Impairment ; Pharmacokinetics ; Dose ; Dementia ; Pharmacy, Therapeutics, & Pharmacology
    ISSN: 1347-8613
    E-ISSN: 1347-8648
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  • 10
    Language: English
    In: Cancer research, 01 January 2012, Vol.72(1), pp.100-11
    Description: Activation of the EGFR, KRAS, and ALK oncogenes defines 3 different pathways of molecular pathogenesis in lung adenocarcinoma. However, many tumors lack activation of any pathway (triple-negative lung adenocarcinomas) posing a challenge for prognosis and treatment. Here, we report an extensive genome-wide expression profiling of 226 primary human stage I-II lung adenocarcinomas that elucidates molecular characteristics of tumors that harbor ALK mutations or that lack EGFR, KRAS, and ALK mutations, that is, triple-negative adenocarcinomas. One hundred and seventy-four genes were selected as being upregulated specifically in 79 lung adenocarcinomas without EGFR and KRAS mutations. Unsupervised clustering using a 174-gene signature, including ALK itself, classified these 2 groups of tumors into ALK-positive cases and 2 distinct groups of triple-negative cases (groups A and B). Notably, group A triple-negative cases had a worse prognosis for relapse and death, compared with cases with EGFR, KRAS, or ALK mutations or group B triple-negative cases. In ALK-positive tumors, 30 genes, including ALK and GRIN2A, were commonly overexpressed, whereas in group A triple-negative cases, 9 genes were commonly overexpressed, including a candidate diagnostic/therapeutic target DEPDC1, that were determined to be critical for predicting a worse prognosis. Our findings are important because they provide a molecular basis of ALK-positive lung adenocarcinomas and triple-negative lung adenocarcinomas and further stratify more or less aggressive subgroups of triple-negative lung ADC, possibly helping identify patients who may gain the most benefit from adjuvant chemotherapy after surgical resection.
    Keywords: Genes, Ras ; Up-Regulation ; Adenocarcinoma -- Genetics ; Erbb Receptors -- Genetics ; Lung Neoplasms -- Genetics ; Receptor Protein-Tyrosine Kinases -- Metabolism
    ISSN: 00085472
    E-ISSN: 1538-7445
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