tbuckley/cabot-search huggingface dataset:
Acupuncture in patients with tension-type headache: randomised controlled trial
Authors: Dieter Melchart, Andrea Streng, Andrea Hoppe, Benno Brinkhaus, Claudia Witt, Stefan Wagenpfeil, Volker Pfaffenrath, Michael Hammes, Josef Hummelsberger, Dominik Irnich, Wolfgang Weidenhammer, Stefan N Willich, Klaus Linde
Journal: BMJ (2005)

Objective To investigate the effectiveness of acupuncture compared with minimal acupuncture and with no acupuncture in patients with tension-type headache. Design Three armed randomised controlled multicentre trial. Setting 28 outpatient centres in Germany. Participants 270 patients (74% women, mean age 43 (SD 13) years) with episodic or chronic tension-type headache. Interventions Acupuncture, minimal acupuncture (superficial needling at non-acupuncture points), or waiting list control. Acupuncture and minimal acupuncture were administered by specialised physicians and consisted of 12 sessions per patient over eight weeks. Main outcome measure Difference in numbers of days with headache between the four weeks before randomisation and weeks 9-12 after randomisation, as recorded by participants in headache diaries. Results The number of days with headache decreased by 7.2 (SD 6.5) days in the acupuncture group compared with 6.6 (SD 6.0) days in the minimal acupuncture group and 1.5 (SD 3.7) days in the waiting list group (difference: acupuncture v minimal acupuncture, 0.6 days, 95% confidence interval -1.5 to 2.6 days, P = 0.58; acupuncture v waiting list, 5.7 days, 3.9 to 7.5 days, P < 0.001). The proportion of responders (at least 50% reduction in days with headache) was 46% in the acupuncture group, 35% in the minimal acupuncture group, and 4% in the waiting list group. Conclusions The acupuncture intervention investigated in this trial was more effective than no treatment but not significantly more effective than minimal acupuncture for the treatment of tension-type headache. Trial registration number [ISRCTN9737659][1]. [1]: /external-ref?link_type=ISRCTN&access_num=ISRCTN9737659
Antibody-Based Profiling of the Phosphoinositide 3-Kinase Pathway in Clinical Prostate Cancer
Authors: George V. Thomas, Steve Horvath, Bradley L. Smith, Katherine Crosby, Lori A. Lebel, Matthew Schrage, Jonathan Said, Jean De Kernion, Robert E. Reiter, Charles L. Sawyers
Journal: Clinical Cancer Research (2004)

Abstract Purpose: As kinase inhibitors transition from the laboratory to patients, it is imperative to develop biomarkers that can be used in the clinic. The primary objectives are to identify patients most likely to benefit from molecularly targeted therapies and to document modulation of the drug target. Constitutive activation of the phosphoinositide 3-kinase (PI3K) pathway and its downstream effectors, as a result of PTEN loss or by other mechanisms, occurs in a high proportion of prostate cancers, making it an ideal template for the design of clinical trials involving PI3K pathway inhibitors. Prostate cancers also present unique organ-specific challenges, in that tumors are heterogeneous and diagnostic tissue is extremely limited. Experimental Design: Working within these limitations, we have developed a set of immunohistochemical assays that define activation of the PI3K pathway in clinical samples. Results and Conclusions: Using both univariate and multivariate analyses, we show that loss of PTEN is highly correlated with the activation of AKT, and this, in turn, is associated with the phosphorylation of S6, one of its main effectors. These three antibodies are potentially able to define a molecular signature of PTEN loss and/or AKT pathway activation in prostate cancer.
The role of human glioma-infiltrating microglia/macrophages in mediating antitumor immune responses1
Authors: S. Farzana Hussain, David Yang, Dima Suki, Kenneth Aldape, Elizabeth Grimm, Amy B. Heimberger
Journal: Neuro-Oncology (2006)

Little is known about the immune performance and interactions of CNS microglia/macrophages in glioma patients. We found that microglia/macrophages were the predominant immune cell infiltrating gliomas (∼1% of total cells); others identified were myeloid dendritic cells (DCs), plasmacytoid DCs, and T cells. We isolated and analyzed the immune functions of CD11b/c+CD45+ glioma-infiltrating microglia/macrophages (GIMs) from postoperative tissue specimens of glioma patients. Although GIMs expressed substantial levels of Toll-like receptors (TLRs), they did not appear stimulated to produce pro-inflammatory cytokines (tumor necrosis factor α, interleukin 1, or interleukin 6), and in vitro, lipopolysaccharides could bind TLR-4 but could not induce GIM-mediated T-cell proliferation. Despite surface major histocompatibility complex class II expression, they lacked expression of the costimulatory molecules CD86, CD80, and CD40 critical for T-cell activation. Ex vivo, we demonstrate a corresponding lack of effector/activated T cells, as glioma-infiltrating CD8+ T cells were phenotypically CD8+CD25-. By contrast, there was a prominent population of regulatory CD4 T cells (CD4+CD25+FOXP3+) infiltrating the tumor. We conclude that while GIMs may have a few intact innate immune functions, their capacity to be stimulated via TLRs, secrete cytokines, upregulate costimulatory molecules, and in turn activate antitumor effector T cells is not sufficient to initiate immune responses. Furthermore, the presence of regulatory T cells may also contribute to the lack of effective immune activation against malignant human gliomas.
Regulatory RNAs: Have mRNA Untranslated Regions Joined the Party?
Authors: Thomas A Hughes, Pamela F Jones
Journal: PLoS Medicine (2008)

In the last decade or so, we have become familiar with the discovery of new classes of nuclear-encoded regulators (see Glossary) as fundamental controllers of gene expression. Each new discovery has again highlighted the incomplete nature of our understanding of the genome and its regulation. First, small interfering RNAs (siRNAs) demonstrated that RNA molecules are not merely components of the cellular machinery (such as tRNAs and rRNAs) or gene-expression intermediates (mRNAs), but can function as potent trans-acting regulators of specific genes. MicroRNAs (miRNAs) continued this theme and now attract much attention among basic scientists and clinicians alike, both as potential regulators of most human genes and as potential diagnostic tools. In this issue of PLoS Medicine, a research article by Shigetada Teshima-Kondo and colleagues supports the suggestion that another class of regulatory RNAs exists [1]. Furthermore, this class could be the largest to date, since potential members are contained within every mRNA.
Nosocomial pneumonia-epidemiological and microbiological characterization of a pulmonology department
Authors: Daniela Madama, Ana Silva, Ana Franco
Journal: European Respiratory Journal (2013)

Introduction  : Nosocomial Pneumonia(NP) can be classified in Health Care Associated(HCAP),Hospital-Acquired(HAP) and Ventilator-Associated(VAP). Objectives  : Characterize the population of patients admitted in a Pulmonology department with the diagnosis of NP and identify the most frequent microorganisms,using a prospective study carried out for 12months. Results: 100patients were included with an average age of 75,08(±12,04),74% were male.The HCAP was the most prevalent(67%),followed by HAP(29%) and VAP(4%)with an average of days of hospitalization of 20,79(±15,15).The length of hospitalization was higher in VAP(27,14).The patients had many co-morbidities associated,with 67% having up to 2.The cardiovascular(49%)and neurological diseases(23%)were the most prevalent.Blood cultures were performed(BC)in 59 patients,with 10% being positive,leading to the identification of Gram+bacteria in 5 cases.The bacteriological examination of sputum(BES) was obtained in 77 patients,but was negative in 44%.Gram + were identified in 18 patients,with the prevalence of MRSA(32%) and in 31 cases,Gram- bacteria were present, A   baumannii  being the most common(32%).Microbiological analysis of bronchial aspirate was performed in 23 cases,identifying the etiologic agent in 19 cases(positivity rate82,6%).The prevalence of MRSA(52%) and  A   baumannii (17,4%)was maintained. Conclusions  : The patients with the diagnosis of NP are old and mainly male,with a high rate of co-morbidities,leading to a high length of hospitalization(over 20 days).Infection by multiresistant bacteria and Gram- is more prevalent,and the most effective microbiological method for identifying bacteria was BES and culture of bronchial aspirate.
Contrast enhanced magnetic resonance imaging of the terminal ileum in children with Crohn's disease
Authors: A Laghi
Journal: Gut (2003)

<b>Background and aims:</b> Recently, magnetic resonance imaging (MRI) has been introduced in the diagnosis of patients with inflammatory bowel disease (IBD). However, it is still rarely reported in paediatric IBD. We studied the diagnostic value of gadolinium enhanced MRI in revealing inflammation of the distal ileum in children with Crohn’s disease (CD) and in differentiating them from patients with other inflammatory diseases of the gut. MRI was performed using a polyethylene glycol (PEG) solution as oral contrast agent to distend the small bowel (CE-PEG-MRI). <b>Subjects and methods:</b> Seventy five consecutive patients (median age 13.6 years, range 8–17) with suspected CD underwent ileocolonoscopy with biopsy and CE-PEG-MRI. CD activity was measured by the paediatric Crohn’s disease activity index (PCDAI). CE-PEG-MRI was evaluated with an overall score calculated, taking into account both wall thickness and contrast enhancement. <b>Results:</b> Active CD with distal ileitis was diagnosed in 26 cases, active ulcerative colitis (UC) in 18, and spondyloarthropathy and indeterminate ileocolitis in 11; 20 children served as controls. In all CD patients, CE-PEG-MRI revealed a marked ileal involvement with increased wall thickness and parietal contrast enhancement and showed a high concordance with endoscopy and histology, whereas the test was negative in all controls. Of the 18 UC patients, CE-PEG-MRI was negative in 15 and showed a mild parietal contrast enhancement of the terminal ileum in only three of seven patients with backwash ileitis. Among the group of spondyloarthropathy patients, six had mucosal erosions and five mild superficial ileitis: CE-PEG-MRI was negative in four and revealed only mild parietal contrast enhancement of the ileal wall in seven. CE-PEG-MRI did not show an increase in wall thickness of the distal ileum in any of the UC or spondyloarthropathy patients. The sensitivity and specificity of CE-PEG-MRI related to the presence of erosive ileitis, as documented by endoscopy, were 84% and 100%, respectively. In addition, the test correlated markedly with endoscopy and histology in the entire population (<i>r</i>=0.94; <i>r</i>=0.95, respectively) as well as with the PCDAI in CD patients (<i>r</i>=0.91). <b>Conclusions:</b> In children with active CD, CE-PEG-MRI is a very sensitive and specific test for the detection of distal ileitis and for differentiation from other inflammatory diseases of the gut. The test could also be useful for the firstline diagnostic approach in children with suspected CD. The high correlation of CE-PEG-MRI with ileal endoscopy and histology as well as with PCDAI makes this test of great interest for future studies as a tool for monitoring the clinical course and the effect of therapy in CD patients.
EZH2 Expression Is Associated With High Proliferation Rate and Aggressive Tumor Subgroups in Cutaneous Melanoma and Cancers of the Endometrium, Prostate, and Breast
Authors: Ingeborg M. Bachmann, Ole J. Halvorsen, Karin Collett, Ingunn M. Stefansson, Oddbjørn Straume, Svein A. Haukaas, Helga B. Salvesen, Arie P. Otte, Lars A. Akslen
Journal: Journal of Clinical Oncology (2005)

EZH2 is a member of the polycomb group of genes and important in cell cycle regulation. Increased expression of EZH2 has been associated previously with invasive growth and aggressive clinical behavior in prostate and breast cancer, but the relationship with tumor cell proliferation has not been examined in human tumors. The purpose of this study was to validate previous findings in a population-based setting, also including tumors that have not been studied previously.In our study of nearly 700 patients, we examined EZH2 expression and its association with tumor cell proliferation and other tumor markers, clinical features, and prognosis in cutaneous melanoma and cancers of the endometrium, prostate, and breast.Strong EZH2 expression was associated with increased tumor cell proliferation in all four cancer types. Associations were also found between EZH2 and important clinicopathologic variables. EZH2 expression showed significant prognostic impact in melanoma, prostate, and endometrial carcinoma in univariate survival analyses, and revealed independent prognostic importance in carcinoma of the endometrium and prostate. CONCLUSION Our findings point at EZH2 as a novel and independent prognostic marker in endometrial cancer, and validate previous findings on prostate and breast cancer. Further, EZH2 expression was associated with features of aggressive cutaneous melanoma. The fact that EZH2 might identify increased tumor cell proliferation and aggressive subgroups in several cancers may be of practical interest because the polycomb group proteins have been suggested as candidates for targeted therapy. EZH2 expression should, therefore, be further examined as a possible predictive factor.
High-throughput analysis of spatio-temporal dynamics in Dictyostelium
Authors: Satoshi Sawai, Xiao-Juan Guan, Adam Kuspa, Edward C Cox
Journal: Genome biology (2007)

Abstract We demonstrate a time-lapse video approach that allows rapid examination of the spatio-temporal dynamics of Dictyostelium cell populations. Quantitative information was gathered by sampling life histories of more than 2,000 mutant clones from a large mutagenesis collection. Approximately 4% of the clonal lines showed a mutant phenotype at one stage. Many of these could be ordered by clustering into functional groups. The dataset allows one to search and retrieve movies on a gene-by-gene and phenotype-by-phenotype basis.
High dose rate endobronchial brachytherapy: results and complications in 189 patients
Authors: M Taulelle, B Chauvet, P Vincent, C Felix-Faure, B Buciarelli, R Garcia, Y Brewer, F Reboul
Journal: European Respiratory Journal (1998)

The purpose of this study was to determine the benefit of high dose rate endobronchial brachytherapy in the treatment of obstructive lung cancer. Between September 1990 and March 1995, 189 patients with bronchogenic carcinoma were treated with high dose rate endobronchial brachytherapy. Most patients (69.3%) had received prior treatment and presented with symptomatic bronchial obstruction due to either recurrent or residual endobronchial disease. A small group (12%) was medically unfit for either surgical resection or thoracic radiotherapy and benefited from endobronchial brachytherapy alone for small endobronchial tumours. The remainder of the patients had not been treated previously and endobronchial brachytherapy was performed for life-threatening symptoms requiring emergency obstruction relief before other therapy. Treatment was performed weekly and consisted of three to four 8 to 10 Gy fractions at a radius of 10 mm from the centre of the source. Major symptomatic relief was obtained for haemoptysis (74%), dyspnoea (54%), and cough (54%). Complete endoscopic response was observed in 54% of cases. Median survival was 7 months for the entire group. For small, strictly endobronchial tumours, complete response rate was 96%, median survival 17 months, and 30 month survival 46%, with a plateau starting at 18 months. Grade 3 to 4 toxicities occurred at a rate of 17% and included massive haemoptysis (n=13), bronchial stenosis (n=12), soft tissue necrosis (n=8), and bronchial fistula (n=3). By univariate analysis, no factor was found to be predictive of late pulmonary toxicity. The present study confirms the usefulness of endobronchial brachytherapy in alleviating symptoms caused by endobronchial recurrence of bronchogenic carcinoma. In addition, this therapy can be tried with curative intent in patients who present with small endobronchial tumours and are not candidates for other forms of therapy.
Neonatal exposure to potent and environmental oestrogens and abnormalities of the male reproductive system in the rat: evidence for importance of the androgen-oestrogen balance and assessment of the relevance to man
Authors: K. Williams
Journal: Human Reproduction Update (2001)

The effects on reproductive tract development in male rats, of neonatal exposure to potent (reference) oestrogens, diethylstilboestrol (DES) and ethinyl oestradiol (EE), with those of two environmental oestrogens, octylphenol and bisphenol A were systematically compared. Other treatments, such as administration of a gonadotrophin-releasing hormone antagonist (GnRHa) or the anti-oestrogen tamoxifen or the anti-androgen flutamide, were used to aid interpretation of the pathways involved. All treatments were administered in the neonatal period before onset of puberty. The cellular sites of expression of androgen receptors (AR) and of oestrogen receptor-α (ERα) and ERβ were also established throughout development of the reproductive system. The main findings were as follows: (i) all cell types that express AR also express one or both ERs at all stages of development; (ii) Sertoli cell expression of ERβ occurs considerably earlier in development than does expression of AR; (iii) most germ cells, including fetal gonocytes, express ERβ but not AR; (iv) treatment with high, but not low, doses of potent oestrogens such as DES and EE, induces widespread structural and cellular abnormalities of the testis and reproductive tract before puberty; (v) the latter changes are associated with loss of immunoexpression of AR in all affected tissues and a reduction in Leydig cell volume per testis; (vi) none of the effects in (iv) and (v) can be duplicated by treating with high-dose octylphenol or bisphenol A; (vi) none of the reproductive tract changes in (iv) and (v) can be induced by simply suppressing androgen production (GnRHa treatment) or action (flutamide treatment); and (vii) the adverse changes induced by high-dose DES (iv and v) can be largely prevented by co-administration of testosterone. Thus, it is suggested that many of the adverse changes to the testis and reproductive tract induced by exposure to oestrogens result from a combination of high oestrogen and low androgen action. High oestrogen action or low androgen action on their own are unable to induce the same changes.
Thrombospondin-1 Is Downregulated by Anoxia and Suppresses Tumorigenicity of Human Glioblastoma Cells
Authors: Mirna Tenan, Giulia Fulci, Michele Albertoni, Annie-Claire Diserens, Marie-France Hamou, Michèle El Atifi-Borel, Jean-Jacques Feige, Michael S. Pepper, Erwin G. Van Meir
Journal: The Journal of Experimental Medicine (2000)

Angiogenesis, the sprouting of new capillaries from preexisting blood vessels, results from a disruption of the balance between stimulatory and inhibitory factors. Here, we show that anoxia reduces expression of thrombospondin-1 (TSP-1), a natural inhibitor of angiogenesis, in glioblastoma cells. This suggests that reduced oxygen tension can promote angiogenesis not only by stimulating the production of inducers, such as vascular endothelial growth factor, but also by reducing the production of inhibitors. This downregulation may significantly contribute to glioblastoma development, since we show that an increase in TSP-1 expression is sufficient to strongly suppress glioblastoma cell tumorigenicity in vivo.
International recommendations for the assessment of autoantibodies to cellular antigens referred to as anti-nuclear antibodies
Authors: Nancy Agmon-Levin, Jan Damoiseaux, Cees Kallenberg, Ulrich Sack, Torsten Witte, Manfred Herold, Xavier Bossuyt, Lucille Musset, Ricard Cervera, Aresio Plaza-Lopez, Carlos Dias, Maria José Sousa, Antonella Radice, Catharina Eriksson, Olof Hultgren, Markku Viander, Munther Khamashta, Stephan Regenass, Luis Eduardo Coelho Andrade, Allan Wiik, Angela Tincani, Johan Rönnelid, Donald B Bloch, Marvin J Fritzler, Edward K L Chan, I Garcia-De La Torre, Konstantin N Konstantinov, Robert Lahita, Merlin Wilson, Olli Vainio, Nicole Fabien, Renato Alberto Sinico, Pierluigi Meroni, Yehuda Shoenfeld
Journal: Annals of the Rheumatic Diseases (2013)

Anti-nuclear antibodies (ANA) are fundamental for the diagnosis of autoimmune diseases, and have been determined by indirect immunofluorescence assay (IIFA) for decades. As the demand for ANA testing increased, alternative techniques were developed challenging the classic IIFA. These alternative platforms differ in their antigen profiles, sensitivity and specificity, raising uncertainties regarding standardisation and interpretation of incongruent results. Therefore, an international group of experts has created recommendations for ANA testing by different methods. Two groups of experts participated in this initiative. The European autoimmunity standardization initiative representing 15 European countries and the International Union of Immunologic Societies/World Health Organization/Arthritis Foundation/Centers for Disease Control and Prevention autoantibody standardising committee. A three-step process followed by a Delphi exercise with closed voting was applied. Twenty-five recommendations for determining ANA (1-13), anti-double stranded DNA antibodies (14-18), specific antibodies (19-23) and validation of methods (24-25) were created. Significant differences between experts were observed regarding recommendations 24-25 (p<0.03). Here, we formulated recommendations for the assessment and interpretation of ANA and associated antibodies. Notably, the roles of IIFA as a reference method, and the importance of defining nuclear and cytoplasmic staining, were emphasised, while the need to incorporate alternative automated methods was acknowledged. Various approaches to overcome discrepancies between methods were suggested of which an improved bench-to-bedside communication is of the utmost importance. These recommendations are based on current knowledge and can enable harmonisation of local algorithms for testing and evaluation of ANA and related autoantibodies. Last but not least, new more appropriate terminologies have been suggested.
Halothane: its Use in Closed Circuit
Authors: H. R. Marrett
Journal: BMJ (1957)

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~fMEDCAL J'OURNAL blood differed from that found when treatment was by a single dose of 2 g.However, the effect on the blood and urine sugars was the same. in both cases.Analyses of plasma amino-acid nitrogen and inorganic phosphorus indicate that tolbutamide has a mode of action different from that of insulin.No toxic effects due to tolbutamide were observed.We express our thanks to the Medical Research Committee of the North-west Metropolitan Regional Hospital Board for a grant to pursue these studies, and also to the Wellcome Founda- tion for -supplies of tolbutamide and placebos.We are grateful to Dr. J.