tbuckley/cabot-search huggingface dataset:
Impact of Prosthesis-Patient Mismatch on Long-Term Survival in Patients With Small St Jude Medical Mechanical Prostheses in the Aortic Position
Authors: Dania Mohty-Echahidi, Joseph F. Malouf, Steve E. Girard, Hartzell V. Schaff, Diane E. Grill, Maurice E. Enriquez-Sarano, Fletcher A. Miller
Journal: Circulation (2006)

The impact of aortic prosthesis-patient mismatch (P-PtM) on long-term survival is unclear.Between 1985 and 2000, 388 patients at Mayo Clinic in Rochester, Minn, underwent aortic valve replacement (AVR) with 19- or 21-mm St Jude Medical prostheses and had transthoracic echocardiography within 1 year after AVR. Mean age of patients was 62+/-13 years; 69% were female. Prosthesis effective orifice area (EOA) was derived from the continuity equation. P-PtM was classified as severe (indexed EOA < or =0.60 cm2/m2), moderate (0.60 cm2/m2<indexed EOA< or =0.85 cm2/m2), or not hemodynamically significant (indexed EOA >0.85 cm2/m2). P-PtM was severe in 66 patients (17%), moderate in 168 (43%), and not hemodynamically significant in 154 (40%). Patients with severe P-PtM had a significantly larger body surface area (P<0.0001), higher mean gradient (P<0.0001), lower preoperative (P<0.0001) and postoperative (P<0.0001) ejection fractions, and lower stroke volume (P<0.0001) and more often received a 19-mm prosthesis (P=0.0008) than patients with moderate or no hemodynamically significant mismatch. For patients with severe mismatch, 5-year survival rates (72+/-6%) and 8-year survival rates (41+/-8%) were significantly less than for patients with moderate mismatch (80+/-3% and 65+/-5%; P=0.026) or no hemodynamically significant mismatch (85+/-3% and 74+/-5%; P=0.002). On multivariate analysis after adjustment for other predictors of outcome, severe mismatch was associated with higher mortality (hazard ratio 2.18; 95% confidence interval 1.24 to 3.85; P=0.007) and higher incidence of congestive heart failure (hazard ratio 3.1; 95% confidence interval 1.3 to 7.4; P=0.009) than no hemodynamically significant mismatch.Severe P-PtM is an independent predictor of higher long-term mortality and congestive heart failure in patients with small St Jude Medical aortic valve prostheses. For patients undergoing AVR who are at risk of severe mismatch, every effort should be made to use a larger prosthesis or to consider a prosthesis with a larger EOA.
Imaging of bronchodilator effects in COPD with hyperpolarised 3He and 1H MRI
Authors: Helen Marshall, Sam Janoff, Juan Parra-Robles, Sam Miller, Stephen Harrison, Martin Deppe, David Lipson, Rod Lawson, Jim Wild
Journal: European Respiratory Journal (2013)

Introduction  A combination of hyperpolarised  3 He and  1 H MRI can provide high spatial resolution images of lung ventilation and blood perfusion, and measurements of lung emphysema.   Objective  To assess regional lung function response to bronchodilator in COPD.   Methods  10 patients with moderate to severe COPD (NICE guidelines) were scanned using  3 He and  1 H MRI, before and after bronchodilator on two occasions. Quantitative MRI measures of ventilation, blood perfusion, apparent diffusion coefficient (ADC) and lung volume were calculated regionally and for the whole lung. Statistical analysis was carried out on the global measures.   Results  After bronchodilator there was a significant decrease in global lung volume suggesting reduced air trapping. No other global MRI measures showed significant change. However, regional changes in ventilation and perfusion were seen after bronchodilator; different lung regions showed different responses, which may account for the lack of significant change globally.  Mean  3 He ADC demonstrated excellent test-retest repeatability at baseline and inverse correlation with DLCO, suggesting that ADC is a reliable measure of emphysematous destruction which shows no change with bronchodilator.   Conclusion  Lung ventilation and perfusion assessment with  3 He and  1 H MRI showed regional variations in response to bronchodilator which were masked by whole lung measurements in this group of patients with moderate to severe COPD.
Association between polymorphism of tumour necrosis factor -308 gene promoter and asthma: a meta-analysis
Authors: J Gao
Journal: Thorax (2006)

<b>Background:</b> Asthma is a complex polygenic disease in which gene–environment interactions are important. The gene encoding tumour necrosis factor alpha (TNFα) is one of several candidate loci for asthma pathogenesis and is highly polymorphic. A number of studies have investigated the polymorphism of TNFα-308 gene promoter (substitution G→A, designated as TNF1 and TNF2) in relation to asthma susceptibility in different populations. However, the results of individual studies have been inconsistent. <b>Methods:</b> To address the inconsistent findings in studies of the association of the polymorphism of TNFα-308 gene promoter with susceptibility to asthma, a systematic review was undertaken of the published data and a meta-analysis was performed. The MEDLINE database was searched for case-control studies published in English language journals from 1966 to October 2005. Data were extracted using standardised forms and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. <b>Results:</b> Fifteen eligible studies, comprising 2409 patients with asthma and 3266 controls, were included in the meta-analysis. Using the random effects model, the pooled result showed that the TNF2 allele is associated with overall susceptibility to asthma (OR 1.37, 95% CI 1.02 to 1.84, p = 0.04). The ORs for asthma susceptibility in TNF2 homozygote individuals were significantly increased at 2.01 (95% CI 1.26 to 3.20, p = 0.009) and 1.51 (95% CI 1.02 to 2.22, p = 0.041) compared with TNF1 homozygotes and TNF2/1 heterozygotes, respectively. In addition, the pooled OR for asthma risk in TNF2/1 heterozygotes was also significantly higher than that in TNF1/1 homozygotes (OR 1.47, 95% CI 1.01 to 2.13, p = 0.045). <b>Conclusions:</b> The TNF2 allele confers a significant risk for developing asthma. A large scale case-control study is needed to clarify the functional effect of the polymorphism of the TNFα gene in the pathogenesis of asthma.
Lysophosphatidic Acid Receptors 1 and 2 Play Roles in Regulation of Vascular Injury Responses but Not Blood Pressure
Authors: Manikandan Panchatcharam, Sumitra Miriyala, Fanmuyi Yang, Mauricio Rojas, Christopher End, Christopher Vallant, Anping Dong, Kevin Lynch, Jerold Chun, Andrew J. Morris, Susan S. Smyth
Journal: Circulation Research (2008)

Phenotypic modulation of vascular smooth muscle cells (SMCs) is essential for the development of intimal hyperplasia. Lysophosphatidic acid (LPA) is a serum component that can promote phenotypic modulation of cultured SMCs, but an endogenous role for this bioactive lipid as a regulator of SMC function in vivo has not been established. Ligation injury of the carotid artery in mice increased levels in the vessel of both autotaxin, the lysophospholipase D enzyme responsible for generation of extracellular LPA, and 2 LPA responsive G protein-coupled receptors 1 (LPA1) and 2 (LPA2). LPA1(-/-)2(-/-) mice were partially protected from the development of injury-induced neointimal hyperplasia, whereas LPA1(-/-) mice developed larger neointimal lesions after injury. Growth in serum, LPA-induced extracellular signal-regulated protein kinase activation, and migration to LPA and serum were all attenuated in SMCs isolated from LPA1(-/-)2(-/-) mice. In contrast, LPA1(-/-) SMCs exhibited enhanced migration resulting from an upregulation of LPA3. However, despite their involvement in intimal hyperplasia, neither LPA1 nor LPA2 was required for dedifferentiation of SMCs following vascular injury or dedifferentiation of isolated SMCs in response to LPA or serum in vitro. Similarly, neither LPA1 nor LPA2 was required for LPA to elicit a transient increase in blood pressure following intravenous administration of LPA to mice. These results identify a role for LPA1 and LPA2 in regulating SMC migratory responses in the context of vascular injury but suggest that additional LPA receptor subtypes are required for other LPA-mediated effects in the vasculature.
The Somatic Symptom Scale–8 (SSS-8)
Authors: Benjamin Gierk, Sebastian Kohlmann, Kurt Kroenke, Lena Spangenberg, Markus Zenger, Elmar Brähler, Bernd Löwe
Journal: JAMA Internal Medicine (2013)

Somatic symptoms are the core features of many medical diseases, and they are used to evaluate the severity and course of illness. The 8-item Somatic Symptom Scale (SSS-8) was recently developed as a brief, patient-reported outcome measure of somatic symptom burden, but its reliability, validity, and usefulness have not yet been tested.To investigate the reliability, validity, and severity categories as well as the reference scores of the SSS-8.A national, representative general-population survey was performed between June 15, 2012, and July 15, 2012, in Germany, including 2510 individuals older than 13 years.The SSS-8 mean (SD), item-total correlations, Cronbach α, factor structure, associations with measures of construct validity (Patient Health Questionnaire-2 depression scale, Generalized Anxiety Disorder-2 scale, visual analog scale for general health status, 12-month health care use), severity categories, and percentile rank reference scores.The SSS-8 had excellent item characteristics and good reliability (Cronbach α = 0.81). The factor structure reflects gastrointestinal, pain, fatigue, and cardiopulmonary aspects of the general somatic symptom burden. Somatic symptom burden as measured by the SSS-8 was significantly associated with depression (r = 0.57 [95% CI, 0.54 to 0.60]), anxiety (r = 0.55 [95% CI, 0.52 to 0.58]), general health status (r = -0.24 [95% CI, -0.28 to -0.20]), and health care use (incidence rate ratio, 1.12 [95% CI, 1.10 to 1.14]). The SSS-8 severity categories were calculated in accordance with percentile ranks: no to minimal (0-3 points), low (4-7 points), medium (8-11 points), high (12-15 points), and very high (16-32 points) somatic symptom burden. For every SSS-8 severity category increase, there was a 53% (95% CI, 44% to 63%) increase in health care visits.The SSS-8 is a reliable and valid self-report measure of somatic symptom burden. Cutoff scores identify individuals with low, medium, high, and very high somatic symptom burden.
Human Dendritic Cells Skew Isotype Switching of CD40-activated Naive B Cells towards IgA1 and IgA2
Authors: Jérôme Fayette, Bertrand Dubois, Stéphane Vandenabeele, Jean-Michel Bridon, Béatrice Vanbervliet, Isabelle Durand, Jacques Banchereau, Christophe Caux, Francine Brière
Journal: The Journal of Experimental Medicine (1997)

Within T cell-rich areas of secondary lymphoid organs, interdigitating dendritic cells recruit antigen-specific T cells that then induce B cells to secrete Igs. This study investigates the possible role(s) of dendritic cells in the regulation of human B cell responses. In the absence of exogenous cytokines, in vitro generated dendritic cells (referred to as Dendritic Langerhans cells, D-Lc) induced surface IgA expression on approximately 10% of CD40-activated naive sIgD+ B cells. In the presence of IL-10 and TGF-beta, a combination of cytokines previously identified for its capacity to induce IgA switch, D-Lc strongly potentiated the induction of sIgA on CD40-activated naive B cells from 5% to 40-50%. D-Lc alone did not induce the secretion of IgA by CD40-activated naive B cells, which required further addition of IL-10. Furthermore, D-Lc skewed towards the IgA isotype at the expense of IgG, the Ig production of CD40-activated naive B cells cultured in the presence of IL-10 and TGF-beta. Importantly, under these culture conditions, both IgA1 and IgA2 were detected. In the presence of IL-10, secretion of IgA2 by CD40-activated naive B cells could be detected only in response to D-Lc and was further enhanced by TGF-beta. Collectively, these results suggest that in addition to activating T cells in the extrafollicular areas of secondary lymphoid organs, human D-Lc also directly modulate T cell-dependent B cell growth and differentiation, by inducing the IgA isotype switch.
Epigenetic regulation of leptin affects MMP-13 expression in osteoarthritic chondrocytes: possible molecular target for osteoarthritis therapeutic intervention
Authors: D Iliopoulos, K N Malizos, A Tsezou
Journal: Annals of the Rheumatic Diseases (2007)

To investigate whether epigenetic mechanisms can regulate leptin's expression and affect its downstream targets as metalloproteinases 3,9,13 in osteoarthritic chondrocytes.DNA methylation in leptin promoter was measured by DNA bisulfite sequencing, and mRNA expression levels were measured by real-time quantitative PCR in osteoarthritic as well as in normal cartilage. Osteoarthritic articular cartilage samples were obtained from two distinct locations of the knee (n = 15); from the main defective area of maximum load (advanced osteoarthritis (OA)) and from adjacent macroscopically intact regions (minimal OA). Using small interference RNA, we tested if leptin downregulation would affect matrix metalloproteinase (MMP)-13 activity. We also evaluated the effect of the demethylating agent, 5'-Aza-2-deoxycytidine (AZA) and of the histone deacetylase inhibitor trichostatin A (TSA) on leptin expression in chondrocyte cultures. Furthermore, we performed chromatin immunoprecipitation in leptin's promoter area.We found a correlation between leptin expression and DNA methylation and also that leptin controls MMP-13 activity in chondrocytes. Leptin's downregulation with small interference RNA inhibited MMP-13 expression dramatically. After 5-AZA application in normal chondrocytes, leptin's methylation was decreased, while its expression was upregulated, and MMP-13 was activated. Furthermore, TSA application in normal chondrocyte cultures increased leptin's expression. Also, chromatin immunoprecipitation in leptin's promoter after TSA treatment revealed that histone H3 lysines 9 and 14 were acetylated.We found that epigenetic mechanisms regulate leptin's expression in chondrocytes affecting its downstream target MMP-13. Small interference RNA against leptin deactivated directly MMP-13, which was upregulated after leptin's epigenetic reactivation, raising the issue of leptin's therapeutic potential for osteoarthritis.
P111 Fluticasone propionate/formoterol fumarate combination therapy is superior to fluticasone propionate alone in improving asthma control
Authors: D. Price, A. Papi, M. Tamm, K. Kaiser, B. Grothe, M. Lomax, T. McIver
Journal: Thorax (2011)

<h3>Introduction and Objectives</h3> Poor asthma control impacts on patients9 health and reduces their quality of life. Despite a rise in the proportion of patients receiving treatment, asthma remains uncontrolled in many patients. A new therapy option combining the inhaled corticosteroid fluticasone propionate (FLUT) with the long-acting ß<sub>2</sub>-agonist formoterol fumarate (FORM) in a single aerosol inhaler (FLUT/FORM; <b><i>flutiform</i><sup>®</sup></b>) has been developed for the treatment of asthma. This integrated analysis of data from five randomised, double-blind, parallel-group phase 3 studies assessed the effects of FLUT/FORM compared with FLUT alone on the percentage of asthma control days. <h3>Methods</h3> Symptomatic adult and adolescent patients with mild, moderate or severe asthma were randomly assigned to receive FLUT/FORM (100/10, 250/10 or 500/20 μg twice daily) or the equivalent nominal dose of FLUT alone (100, 250 or 500 μg twice daily) for 8 or 12 weeks. Most patients randomised to treatment had uncontrolled asthma. The percentage change in asthma control days (defined as those with no use of rescue medication, an asthma symptom score reporting no symptoms and a sleep disturbance score indicating that the patient slept through the night) was assessed from baseline to study end. <h3>Results</h3> At baseline, the percentage of asthma control days was low in both groups (FLUT/FORM [n=623]: 12.8%; FLUT [n=623]: 12.6%). FLUT/FORM combination therapy was superior to FLUT alone for improvement in percentage of asthma control days. At study end, patients in the FLUT/FORM group experienced a mean of 62.4% asthma control days, an improvement of 49.6% from baseline, whereas FLUT treatment was associated with 54.8% asthma control days (42.2% change from baseline). FLUT/FORM provided a statistically significant improvement in asthma control days compared with FLUT alone (least-squares mean difference [95% CI]: 7.5% [3.21 to 11.84]; p&lt;0.001). <h3>Conclusions</h3> Fluticasone/formoterol combination therapy is superior to fluticasone monotherapy for improving the percentage of asthma control days over 8 or 12 weeks9 treatment in adults and adolescents with mild, moderate or severe asthma. These data suggest the combination of fluticasone and formoterol in a single aerosol inhaler will provide an effective option for asthma maintenance therapy.
Profile of Patients With Kaposi's Sarcoma in the Era of Highly Active Antiretroviral Therapy
Authors: James H. Gallafent, Susan E. Buskin, Peter B. De Turk, David M. Aboulafia
Journal: Journal of Clinical Oncology (2005)

Purpose Since the advent of highly active antiretroviral therapy (HAART), the incidence of Kaposi's sarcoma (KS) among AIDS patients has declined both nationwide and in King County, Washington. We sought to compare clinical parameters of patients diagnosed with KS in the pre-HAART (1990 to 1996) and HAART (1997 to 2002) eras. Methods We used patient data abstracted from the Adult/Adolescent Spectrum of HIV-Related Diseases study of Public Health—Seattle and King County. Results Patients diagnosed with KS in the HAART era (n = 40) were significantly more likely (P &lt; .05) than pre–HAART-era KS patients (n = 366) to be diagnosed with alcohol problems (43% v 18%), noninjection drug use (45% v 18%), injection drug use (25% v 10%), psychosis (25% v 13%), and hypertension (13% v 2%). Although median CD4 + count and HIV-1 viral load at the time of KS diagnosis were not significantly different between the two groups, significantly fewer (P &lt; .01) HAART-era KS patients developed opportunistic illnesses (OIs) during their follow-up. The risk of dying among KS patients diagnosed in the HAART era is significantly lower (P &lt; .01) than for KS patients diagnosed in the pre-HAART era (hazard ratio, 0.24). Conclusion Although HAART-era KS patients in King County were as likely to have a depleted CD4 + cell count and high HIV-1 viral loads at the time of KS diagnosis as pre-HAART KS patients, they survived longer and fewer of them were diagnosed with other OIs. They also had an increased prevalence of substance abuse and mental illness, contributing to a dynamic and changing KS clinical profile.
Anticardiolipin antibodies recognize beta 2-glycoprotein I structure altered by interacting with an oxygen modified solid phase surface.
Authors: E Matsuura, Y Igarashi, T Yasuda, D A Triplett, T Koike
Journal: The Journal of Experimental Medicine (1994)

Anticardiolipin antibodies (aCL) derived from the sera of individuals exhibiting the antiphospholipid syndrome (APS) directly bind to beta 2-glycoprotein I (beta 2-GPI), which is adsorbed to an oxidized polystyrene surface. Oxygen atoms were introduced on a polystyrene surface by irradiation with electron or gamma-ray radiation. X-ray photoelectron spectroscopy revealed the irradiated surfaces were oxidized to generate C-O and C = O moieties. aCL derived from either APS patients or (NZW x BXSB)F1 mice bound to beta 2-GPI coated on the irradiated plates, depending on the radiation dose. Antibody binding to beta 2-GPI on the irradiated plates was competitively inhibited by simultaneous addition of cardiolipin (CL)-coated latex beads mixed together with beta 2-GPI but were unaffected by addition of excess beta 2-GPI, CL micelles, or CL-coated latex beads alone. There was a high correlation between binding values of aCL in sera from 40 APS patients obtained by the anti-beta 2-GPI enzyme-linked immunosorbent assay (ELISA) using the irradiated plates and those by the beta 2-GPI-dependent aCL ELISA. Therefore, aCL have specificity for an epitope on beta 2-GPI. This epitope is expressed by a conformational change occurring when beta 2-GPI interacts with an oxygen-substituted solid phase surface.
Predicting Resistance or Response to Chemotherapy by Proton Magnetic Resonance Spectroscopy in Neuroblastoma
Authors: Magnus Lindskog, Christian Spenger, Jüri Jarvet, Astrid Gräslund, Per Kogner
Journal: JNCI Journal of the National Cancer Institute (2004)

We previously showed that proton magnetic resonance spectroscopy (1H-MRS) enables estimation of neuroblastoma tumor viability. Here we investigated if 1H-MRS can predict response or resistance to chemotherapy in neuroblastoma.Neuroblastoma cell lines with various drug sensitivities were treated with cytotoxic drugs (cisplatin, etoposide, and irinotecan) and examined by 1H-MRS. Viability was assessed by trypan blue staining and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Nude rats carrying drug-sensitive or drug-resistant neuroblastoma xenografts were treated for 4 days with irinotecan (n = 11) or saline (n = 11) and were examined with 1H-MRS at 4.7 T before and during treatment. The Wilcoxon matched-pairs test was used to test statistical significance of difference within treatment groups. Independent groups were compared using the Mann-Whitney U test. Correlation was assessed with Spearman's rank correlation. All statistical tests were two-sided.Cytotoxic drug treatment of drug-sensitive SH-SY5Y neuroblastoma cells resulted in increased methylene and polyunsaturated fatty acid resonances and decreased choline resonance. The methylene/choline ratio correlated with cell death (r(s) = .94, P<.001) and was increased in cisplatin-treated drug-sensitive (SH-SY5Y, IMR-32) but not drug-resistant [SK-N-BE2, SK-N-FI, SK-N-AS] cell lines. No changes were observed in SK-N-BE2 cells treated with irinotecan or cisplatin, whereas circumvention of the resistance by arsenic trioxide treatment led to lipid accumulation and choline depletion. Irinotecan therapy of rats carrying drug-sensitive xenografts caused the methylene/choline ratio of tumors to increase eightfold after 3 days (95% confidence interval [CI] = fivefold to 12-fold; P = .005 compared with pretreatment spectra at day 0) and caused tumors to regress statistically significantly on day 10 compared with pretreatment volume on day 0 (difference = -60%, 95% CI = -12% to -100%, n = 6; P = .012). The methylene/choline ratio of nonregressing drug-resistant xenografts was unaffected. No differences were observed after saline treatment.Response or resistance to chemotherapy is accurately predicted by 1H-MRS in experimental neuroblastoma models in vivo.