tbuckley/cabot-search huggingface dataset:
Prevalence of respiratory and atopic disorders among children in the East and West of Germany five years after unification
Authors: S.K. Weiland, E. von Mutius, T Hirsch, H. Duhme, C Fritzsch, B. Werner, A. Hüsing, M. Stender, H Renz, W Leupold, U. Keil
Journal: European Respiratory Journal (1999)

Living conditions in eastern Germany have changed rapidly since unification in 1990 and little is known about how these changes affect the prevalence of atopic diseases. This study describes methods and prevalences of a large epidemiological project investigating determinants of childhood asthma and allergies in eastern (Dresden and Leipzig) and western (Munich) Germany in 1995/1996. Community based random samples of 9-11 yr old children in Dresden (n=3,017) and Munich (n=2,612), and of 5-7 yr old children in Dresden (n=3,300), Leipzig (n=3,167) and Munich (n=2,165) were studied by parental questionnaires, bronchial challenges with hypertonic saline, skin examination, skin-prick tests, and measurements of specific and total serum immunoglobulin (Ig)E using Phase II modules of the International Study of Asthma and Allergies in Childhood (ISAAC). In 9-11 yr old children, the prevalence of physician diagnosed asthma (7.9% versus 10.3%; p<0.01) and bronchial hyperresponsiveness (15.7% versus 19.9%; p<0.05) was lower in Dresden than in Munich. No difference between Munich and Dresden was observed in the prevalence of diagnosed hay fever, skin test reactivity to > or = 1 allergen, and increased levels (>0.35 kU x L(-1)) of specific IgE against inhalant and food allergens. Symptoms and visible signs of atopic eczema tended to be more prevalent in Dresden. Similar East-West differences between the three study areas were seen in the younger age group. These findings are in line with recently observed increases in the prevalence of hay fever and atopic sensitization, but not of asthma and bronchial hyperresponsiveness, among 9-11 yr old children in Leipzig.
Two-Year Outcomes of “Treat and Extend” Intravitreal Therapy for Neovascular Age-Related Macular Degeneration
Authors: Jennifer J. Arnold, Anna Campain, Daniel Barthelmes, Judy M. Simpson, Robyn H. Guymer, Alex P. Hunyor, Ian L. McAllister, Rohan W. Essex, Nigel Morlet, Mark C. Gillies, A. Hunt, M. Gillies, A. Hunt, A.P. Hunyor, J. Arnold, S. Young, G. Clark, Gayatri Banerjee, R. Phillips, M. Perks, R. Essex, I. McAllister, I. Constable, R. Guymer, R. Guymer, L. Lim, A. Harper, L.P. Chow, S. Wickremansinghe, S. Wickremasinghe, S. Wickremasinghe
Journal: Ophthalmology (2015)
Representing infant feeding: content analysis of British media portrayals of bottle feeding and breast feeding
Authors: L. Henderson
Journal: BMJ (2000)

<b><i>Background:</i></b> In polyneuropathy associated with immunoglobulin M (IgM) monoclonal gammopathy, antibodies to myelin-associated glycoprotein (MAG), sulfoglucuronyl paragloboside (SGPG), and sulfatide have been associated with specific clinical and electrophysiologic features. However, it is not known whether the results of antibody tests provide additional information for the individual patient (and the neurologist) in terms of future neurologic deficit or outcome. <b><i>Objective:</i></b> To study the independent contribution of potential prognostic factors to the prediction of outcome of neuropathy associated with IgM monoclonal gammopathy. <b><i>Methods:</i></b> In accordance with the chronology in which prognostic factors are available in clinical practice, the association between prognostic factors and outcome was evaluated by univariate and multivariate logistic regression analysis in 65 patients with polyneuropathy and IgM monoclonal gammopathy. <b><i>Results:</i></b> In univariate analysis, the initial symptoms, the IgM light chain type, electrophysiologic and pathologic studies, the presence of sural nerve IgM deposition, and anti-MAG or anti-SGPG antibodies were significantly associated with outcome. However, multivariate analysis showed that only initial symptoms and electrophysiologic studies are independent prognostic factors: initial sensory symptoms of the feet are prognostic for a slowly progressive disease course and less disability at 4 years, and evidence for demyelination on electrophysiologic examination is prognostic for development of weakness and symptoms of the upper extremities at 4 years. Addition of anti-MAG or anti-SGPG antibody tests did not yield any additional prediction of outcome. <b><i>Conclusion:</i></b> These results indicate that in clinical practice, antibody tests in polyneuropathy associated with IgM monoclonal gammopathy do not have a prognostic value in terms of future neurologic deficit or outcome.
Short term and long term detraining: is there any difference between young-old and old people?
Authors: N F Toraman
Journal: British Journal of Sports Medicine (2005)

Objectives: To assess the effects of short (six weeks) and long (52 weeks) term detraining on functional fitness in elderly people, and to determine whether these effects differ according to age in elderly people. Methods: Elderly subjects, aged 60–86 years, completed a nine week multicomponent exercise training programme. They performed the senior fitness test after six and 52 weeks, and the responses of 12 young-old subjects (YO, aged 60–73 years) and nine older subjects (O, aged 74–86 years) were compared. Results: Functional fitness improved during the exercise training period. Short term detraining caused a loss of this improvement in functional performance. Performance on the chair stand test for both YO and O groups and on the up and go and six minute walk tests for the YO group remained significantly higher than before training after six weeks of detraining (p&lt;0.013). Performance in all tests reverted to the pre-training values or lower after 52 weeks of detraining in both groups. In the O group, performances in the six minute walk test and arm curl test were lower than before training (p&lt;0.013). The components of functional fitness most affected by detraining were agility with short term detraining, and aerobic endurance and upper extremity strength with long term detraining. Conclusion: Changes in functional capacity after short and long term detraining are affected by age in elderly adults.
Ly6c+ “inflammatory monocytes” are microglial precursors recruited in a pathogenic manner in West Nile virus encephalitis
Authors: Daniel R. Getts, Rachael L. Terry, Meghann Teague Getts, Marcus Müller, Sabita Rana, Bimmi Shrestha, Jane Radford, Nico Van Rooijen, Iain L. Campbell, Nicholas J.C. King
Journal: The Journal of Experimental Medicine (2008)

In a lethal West Nile virus (WNV) model, central nervous system infection triggered a threefold increase in CD45(int)/CD11b(+)/CD11c(-) microglia at days 6-7 postinfection (p.i.). Few microglia were proliferating, suggesting that the increased numbers were derived from a migratory precursor cell. Depletion of "circulating" (Gr1(-)(Ly6C(lo))CX3CR1(+)) and "inflammatory" (Gr1(hi)/Ly6C(hi)/CCR2(+)) classical monocytes during infection abrogated the increase in microglia. C57BL/6 chimeras reconstituted with cFMS-enhanced green fluorescent protein (EGFP) bone marrow (BM) showed large numbers of peripherally derived (GFP(+)) microglia expressing GR1(+)(Ly6C(+)) at day 7 p.i., suggesting that the inflammatory monocyte is a microglial precursor. This was confirmed by adoptive transfer of labeled BM (Ly6C(hi)/CD115(+)) or circulating inflammatory monocytes that trafficked to the WNV-infected brain and expressed a microglial phenotype. CCL2 is a chemokine that is highly expressed during WNV infection and important in inflammatory monocyte trafficking. Neutralization of CCL2 not only reduced the number of GFP(+) microglia in the brain during WNV infection but prolonged the life of infected animals. Therefore, CCL2-dependent inflammatory monocyte migration is critical for increases in microglia during WNV infection and may also play a pathogenic role during WNV encephalitis.
CHLORPROMAZINE IN THE TREATMENT OF MENTAL ILLNESS. IV: FINAL RESULTS WITH ANALYSIS OF DATA ON 1,523 PATIENTS
Authors: HERMAN C. B. DENBER, ETTA G. BIRD
Journal: American Journal of Psychiatry (1957)

1. Of 1, 523 patients treated with chlorpromazine from 1-15 months, 81.8% showed improvement. 2. Problems concerning dose, side-effects, and clinical results have been considered. 3. Female patients used higher doses, had a proportionately larger number of sideeffects, and showed a better discharge rate than males. 4. Some theoretical considerations of these findings have been reviewed.
Hypoexpression and Epigenetic Regulation of Candidate Tumor Suppressor Gene <i>CADM-2</i> in Human Prostate Cancer
Authors: Guimin Chang, Shuping Xu, Rajiv Dhir, Uma Chandran, Denise S. O'Keefe, Norman M. Greenberg, Jeffrey R. Gingrich
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Cell adhesion molecules (CADM) comprise a newly identified protein family whose functions include cell polarity maintenance and tumor suppression. CADM-1, CADM-3, and CADM-4 have been shown to act as tumor suppressor genes in multiple cancers including prostate cancer. However, CADM-2 expression has not been determined in prostate cancer. Experimental Design: The CADM-2 gene was cloned and characterized and its expression in human prostatic cell lines and cancer specimens was analyzed by reverse transcription-PCR and an immunohistochemical tissue array, respectively. The effects of adenovirus-mediated CADM-2 expression on prostate cancer cells were also investigated. CADM-2 promoter methylation was evaluated by bisulfite sequencing and methylation-specific PCR. Results: We report the initial characterization of CADM-2 isoforms: CADM-2a and CADM-2b, each with separate promoters, in human chromosome 3p12.1. Prostate cancer cell lines, LNCaP and DU145, expressed negligible CADM-2a relative to primary prostate tissue and cell lines, RWPE-1 and PPC-1, whereas expression of CADM-2b was maintained. Using immunohistochemistry, tissue array results from clinical specimens showed statistically significant decreased expression in prostate carcinoma compared with normal donor prostate, benign prostatic hyperplasia, prostatic intraepithelial neoplasia, and normal tissue adjacent to tumor (P &amp;lt; 0.001). Adenovirus-mediated CADM-2a expression suppressed DU145 cell proliferation in vitro and colony formation in soft agar. The decrease in CADM-2a mRNA in cancer cell lines correlated with promoter region hypermethylation as determined by bisulfite sequencing and methylation-specific PCR. Accordingly, treatment of cells with the demethylating agent 5-aza-2′-deoxycytidine alone or in combination with the histone deacetylase inhibitor trichostatin A resulted in the reactivation of CADM-2a expression. Conclusions: CADM-2a protein expression is significantly reduced in prostate cancer. Its expression is regulated in part by promoter methylation and implicates CADM-2 as a previously unrecognized tumor suppressor gene in a proportion of human prostate cancers. Clin Cancer Res; 16(22); 5390–401. ©2010 AACR.
Ultrastructural localisation of alkaline phosphatase activity in osteoarthritic human articular cartilage.
Authors: J A Rees, S Y Ali
Journal: Annals of the Rheumatic Diseases (1988)

The distribution of alkaline phosphatase activity in human articular cartilage from normal and osteoarthritic joints has been examined by an electron microscope technique, probably for the first time. In osteoarthritic cartilage chondrocytes and matrix vesicles close to the tidemark were positive for alkaline phosphatase activity. Large numbers of matrix vesicles were found within the extracellular matrix of osteoarthritic cartilage, and there is a specific relation between phosphatase activity, matrix vesicles, and initial mineral formation in the tidemark region of articular cartilage.
Predictive and Prognostic Value of Peripheral Blood Cytokeratin-19 mRNA-Positive Cells Detected by Real-Time Polymerase Chain Reaction in Node-Negative Breast Cancer Patients
Authors: Nikos Xenidis, Maria Perraki, Maria Kafousi, Stella Apostolaki, Irene Bolonaki, Aliki Stathopoulou, Kostas Kalbakis, Nikos Androulakis, Charalambos Kouroussis, Thanos Pallis, Charalambos Christophylakis, Katerina Argyraki, Evi S. Lianidou, Stathis Stathopoulos, Vassilis Georgoulias, Dimitris Mavroudis
Journal: Journal of Clinical Oncology (2006)

To evaluate the predictive and prognostic value of peripheral blood cytokeratin-19 (CK-19) mRNA-positive cells in axillary lymph node-negative breast cancer patients.Peripheral blood was obtained from 167 node-negative breast cancer patients before the initiation of any systemic adjuvant therapy, and was analyzed for the presence of CK-19 mRNA-positive cells using a real time polymerase chain reaction assay. The association with known prognostic factors and the effect of CK-19 mRNA-positive cells on patients' prognosis was investigated.CK-19 mRNA-positive cells were detected in the blood of 36 (21.6%) of the 167 patients. There was no correlation between the detection of CK-19 mRNA-positive cells in the peripheral blood and the various known pathologic and clinical prognostic factors; only overexpression of HER2 receptor (score 2+/3+) on the primary tumor was associated with a higher incidence of CK-19 mRNA-positive cell detection (P = .033). Multivariate analysis revealed that detection of peripheral blood CK-19 mRNA-positive cells was associated with early clinical relapse (P < .00001) and disease-related death (P = .008).Detection of peripheral-blood CK-19 mRNA-positive cells is an independent predictive and prognostic factor for reduced disease-free interval and overall survival, respectively, in node-negative breast cancer patients.
Duration of the initial TCR stimulus controls the magnitude but not functionality of the CD8+ T cell response
Authors: Martin Prlic, Gabriela Hernandez-Hoyos, Michael J. Bevan
Journal: The Journal of Experimental Medicine (2006)

CD8+ T cells only require a brief stimulation with antigen in vitro to divide and differentiate into effector and memory cells upon transfer in vivo. The efficiency of clonal expansion and the functional characteristics of memory cells derived from briefly stimulated cells are poorly defined. We developed a system that allowed us to examine programming entirely in vivo. This was achieved by rapidly killing peptide-pulsed DCs carrying a diphtheria toxin receptor transgene with timed injections of diphtheria toxin without altering the course of an accompanying infection. The magnitude of clonal expansion, but not the functionality of the effector cells, correlated directly with the duration of antigen exposure. Furthermore, memory T cells were capable of mounting a secondary response, regardless of the length of antigen encounter during the primary response. These results indicate that the duration of initial antigen encounter influences the magnitude of the primary response, but does not program responsiveness during the secondary challenge.
Central adiposity, regional fat distribution, and the risk of cholecystectomy in women
Authors: C-J Tsai
Journal: Gut (2006)

Whether central adiposity contributes independently of total adiposity to the risk for gall stones is inconclusive. We examined prospectively indicators of central adiposity in relation to the occurrence of gall stone disease.We evaluated the relationship between abdominal circumference and waist to hip ratio and risk of cholecystectomy in a cohort of women who had no history of gall stone disease. As part of the Nurses' Health Study, the women reported on questionnaires their weights, heights, and waist and hip circumferences, and the occurrence of cholecystectomy. A total of 42,312 women, aged 39-66 years in 1986, who were free of prior gall stone disease, provided complete waist and hip circumference measurements in 1986.We documented 3197 cases of cholecystectomy during 514,283 person years of follow up. After adjusting simultaneously for regional (waist circumference or waist to hip ratio) and total adiposity (body mass index) measures as well as for other risk factors of gall stone disease, women with a height adjusted waist circumference of 36 inches or larger had a relative risk (RR) of 1.96 (95% confidence interval (CI) 1.53-2.51; p trend < 0.0001) compared with women with a height adjusted waist circumference of less than 26 inches. Waist to hip ratio was directly associated with the risk, with an RR of 1.39 (95% CI 1.16-1.66; p trend < 0.0001) for women with a waist to hip ratio of 0.86 or higher compared with women with a waist to hip ratio of less than 0.70.Abdominal circumference and waist to hip ratio were associated with an increased risk of cholecystectomy, independently of body mass index in women.
Adenoviral-mediated gene transfer induces sustained pericardial VEGF expression in dogs: effect on myocardial angiogenesis
Authors: D Lazarous
Journal: Cardiovascular Research (1999)

Angiogenic peptides like VEGF (vascular endothelial growth factor) and bFGF (basic fibroblast growth factor) have entered clinical trials for coronary artery disease. Attempts are being made to devise clinically relevant means of delivery and to effect site-specific delivery of these peptides to the cardiac tissue, in order to limit systemic side-effects. We characterized the response of the pericardium to delivery of a replication-deficient adenovirus carrying the cDNA for AdCMV.VEGF165, and assessed the effect of pericardial VEGF165 on myocardial collateral development in a canine model of progressive coronary occlusion.Ameroid constrictors were placed on the proximal left circumflex coronary artery of mongrel dogs. Ten days later, 6 x 10(9) pfu AdCMV.VEGF165 (n = 9). AdRSV.beta-gal (n = 9), or saline (n = 7) were injected through an indwelling pericardial catheter. Transfection efficiency was assessed by X-gal staining. Pericardial and serum VEGF levels were measured serially by ELISA. Maximal myocardial collateral perfusion was quantified with radiolabeled or fluorescent microspheres 28 days after treatment.In AdRSV.beta-gal-treated dogs, there was extensive beta-gal staining in the pericardium and epicardium, with minimal beta-gal staining in the mid-myocardium and endocardium. Pericardial delivery of AdCMV.VEGF165 resulted in sustained (8-14 day) pericardial transgene expression, with VEGF levels peaking 3 days after infection (> 200 ng/ml) and decreasing thereafter. There was no detectable increase in serum VEGF levels. Maximal collateral perfusion, a principal correlate of collateral development and angiogenesis, was equivalent in all groups.Adenoviral-mediated gene transfer is capable of inducing sustained VEGF165 expression in the pericardium; however, locally targeted pericardial VEGF delivery failed to improve myocardial collateral perfusion in this model.
Innovative research methods for studying treatments for rare diseases: methodological review
Authors: J. J. Gagne, L. Thompson, K. O'Keefe, A. S. Kesselheim
Journal: BMJ (2014)

To examine methods for generating evidence on health outcomes in patients with rare diseases.Methodological review of existing literature.PubMed, Embase, and Academic Search Premier searched for articles describing innovative approaches to randomized trial design and analysis methods and methods for conducting observational research in patients with rare diseases.We assessed information related to the proposed methods, the specific rare disease being studied, and outcomes from the application of the methods. We summarize methods with respect to their advantages in studying health outcomes in rare diseases and provide examples of their application.We identified 46 articles that proposed or described methods for studying patient health outcomes in rare diseases. Articles covered a wide range of rare diseases and most (72%) were published in 2008 or later. We identified 16 research strategies for studying rare disease. Innovative clinical trial methods minimize sample size requirements (n=4) and maximize the proportion of patients who receive active treatment (n=2), strategies crucial to studying small populations of patients with limited treatment choices. No studies describing unique methods for conducting observational studies in patients with rare diseases were identified.Though numerous studies apply unique clinical trial designs and considerations to assess patient health outcomes in rare diseases, less attention has been paid to innovative methods for studying rare diseases using observational data.
Association of Clopidogrel Pretreatment With Mortality, Cardiovascular Events, and Major Bleeding Among Patients Undergoing Percutaneous Coronary Intervention
Authors: Anne Bellemain-Appaix, Stephen A. O’Connor, Johanne Silvain, Michel Cucherat, Farzin Beygui, Olivier Barthélémy, Jean-Philippe Collet, Laurent Jacq, François Bernasconi, Gilles Montalescot, for the ACTION group
Journal: JAMA (2012)

Clopidogrel pretreatment is recommended for patients with acute coronary syndromes (ACS) and stable coronary artery disease who are scheduled for percutaneous coronary intervention (PCI), but whether using clopidogrel as a pretreatment for PCI is associated with positive clinical outcomes has not been established.To evaluate the association of clopidogrel pretreatment vs no treatment with mortality and major bleeding after PCI.MEDLINE, EMBASE, Cochrane Controlled Trials Register databases, and reference lists of qualifying articles. STUDY SELECTION Studies reporting clinical data on mortality and major bleeding were included. Of the 392 titles identified, 15 articles published between August 2001 and September 2012 met the inclusion criteria: 6 randomized controlled trials (RCTs), 2 observational analyses of RCTs, and 7 observational studies.Quality of studies was assessed with the Ottawa Scale and the Jadad Score as appropriate. Results were independently extracted by 2 reviewers. A random-effect model was applied. Pretreatment was defined as the administration of clopidogrel before PCI or catheterization. The main analysis was performed on RCTs and confirmed by observational analyses and observational studies. Prespecified subgroups--clinical presentation and clopidogrel loading dose--were analyzed. The primary efficacy and safety end points were all-cause mortality and major bleeding. Secondary end points included major cardiac events.Of the 37 814 patients included in the meta-analysis, 8608 patients had participated in RCTs; 10,945, in observational analyses of RCTs; and 18,261, in observational studies. Analysis of RCTs showed that clopidogrel pretreatment was not associated with a reduction of death (absolute risk, 1.54% vs 1.97%; OR, 0.80; 95% CI, 0.57-1.11; P = .17) but was associated with a lower risk of major cardiac events (9.83% vs 12.35%; OR, 0 .77; 95% CI, 0.66-0.89; P < .001). There was no significant association between pretreatment and major bleeding overall (3 .57% vs 3.08%; OR, 1.18; 95% CI, 0.93-1.50; P = .18). Analyses from observational analyses of RCTs and observational studies were consistent for all results.Among patients scheduled for PCI, clopidogrel pretreatment was not associated with a lower risk of mortality but was associated with a lower risk of major coronary events.