tbuckley/cabot-search huggingface dataset:
Exhaled nitric oxide thresholds associated with a sputum eosinophil count &gt;=3% in a cohort of unselected patients with asthma
Authors: F. N. Schleich, L. Seidel, J. Sele, M. Manise, V. Quaedvlieg, A. Michils, R. Louis
Journal: Thorax (2010)

It has been claimed that exhaled nitric oxide (FeNO) could be regarded as a surrogate marker for sputum eosinophil count in patients with asthma. However, the FeNO threshold value that identifies a sputum eosinophil count ≥3% in an unselected population of patients with asthma has been poorly studied.This retrospective study was conducted in 295 patients with asthma aged 15–84 years recruited from the asthma clinic of University Hospital of Liege. Receiver-operating characteristic (ROC) curve and logistic regression analysis were used to assess the relationship between sputum eosinophil count and FeNO, taking into account covariates such as inhaled corticosteroids (ICS), smoking, atopy, age and sex.Derived from the ROC curve, FeNO ≥41 ppb gave 65% sensitivity and 79% specificity (AUC=0.777, p=0.0001) for identifying a sputum eosinophil count ≥3%. Using logistic regression analysis, a threshold of 42 ppb was found to discriminate between eosinophilic and non-eosinophilic asthma (p<0.0001). Patients receiving high doses of ICS (≥1000 μg beclometasone) had a significantly lower FeNO threshold (27 ppb) than the rest of the group (48 ppb, p<0.05). Atopy also significantly altered the threshold (49 ppb for atopic vs 30 ppb for non-atopic patients, p<0.05) and there was a trend for a lower threshold in smokers (27 ppb) compared with non-smokers (46 ppb, p=0.066). Age and sex did not affect the relationship between FeNO and sputum eosinophilia. When combining all variables into the logistic model, FeNO (p<0.0001), high-dose ICS (p<0.05) and smoking (p<0.05) were independent predictors of sputum eosinophilia, while there was a trend for atopy (p=0.086).FeNO is able to identify a sputum eosinophil count ≥3% with reasonable accuracy and thresholds which vary according to dose of ICS, smoking and atopy.
Colon mucosa of patients both with spondyloarthritis and Crohn's disease is enriched with macrophages expressing the scavenger receptor CD163
Authors: P Demetter
Journal: Annals of the Rheumatic Diseases (2004)

<b>Background:</b> Crohn's disease is associated with an increased number of macrophages in ileal and colonic mucosa. Data on macrophages in gut mucosa of patients with spondyloarthritis (SpA) are scarce. <b>Objective:</b> To investigate macrophages and other antigen presenting cells in gut mucosa from patients with SpA and Crohn's disease, given the relationship between both entities. <b>Methods:</b> Biopsy specimens from patients with SpA, Crohn's disease, ulcerative colitis, and from controls were immunohistochemically stained with different markers for macrophages and dendritic cells. Slides were scored semiquantitatively on a four point scale. <b>Results:</b> SpA and Crohn's disease were associated with large numbers of CD68<sup>+</sup> macrophages. Colon mucosa of both patients with SpA and Crohn's disease, but not ulcerative colitis, showed increased numbers of macrophages expressing the scavenger receptor CD163. <b>Conclusions:</b> Macrophages expressing the scavenger receptor CD163 are increased in colonic mucosa in SpA and in Crohn's disease, highlighting the relationship between these entities. The increased number of CD163<sup>+</sup> macrophages in colon mucosa of patients with SpA suggests this is another argument for a role of macrophage scavenger receptors in this group of diseases.
Murine B-cell subpopulations responsive to T-dependent and T-independent antigens.
Authors: G K Lewis, R Ranken, D E Nitecki, J W Goodman
Journal: The Journal of Experimental Medicine (1976)

Strain A/J mice made secondary indirect plaque-forming cell (PFC) responses to azobenzenearsonate (ABA) conjugates of giant keyhole limpet hemocyanin (KLH), a thymic-dependent antigen, but not to conjugates of Ficoll, a T-independent antigen. ABA-Ficoll was also unable to elicit a response in animals primed with ABA-KLH, which have an expanded anti-ABA memory cell pool. On the other hand, ABA-Ficoll rendered mice unresponsive to ABA-KLH when administered before priming or boosting with the T-dependent immunogen. Hence, the T-independent antigen was able to tolerize but unable to trigger B-memory cells responsive to the T-dependent antigen. A/J mice immunized with dinitrophenyl conjugates of Ficoll or bovine IgG (BGG) made vigorous IgM and IgG PFC responses. PFC responses to ABA-KLH and 2,4-dinitrophenyl (DNP)-BGG were abrogated by depleting mice of C3 with cobra venom factor, whereas the IgM and IgG PFC responses to DNP-Ficoll were unaffected. B lymphocytes were fractionated on the basis of receptors for C3 and the subpopulations were assayed for in vitro PFC responses to DNP-Ficoll. Very little response was obtained from complement receptor lymphocyte [CRL(+)] B cells, whereas CRL(-) cells were more responsive than unfractionated B cells. Both populations responded to a polyclonal B-cell mitogen (lipopolysaccharide). On the other hand, the in vitro PFC response to a T-dependent antigen (sheep erythrocytes) correlated with the presence of CRL(+) B cells in the cultures. However, a minor component of this response, sensitive to anti-Thy-1 serum, was made by CRL(-) B cells, indicating the existence of subpopulations of T-dependent B cells with different signalling requirements. The results suggest that most B cells responsive to T-dependent antigens possess receptors for C3 and that C3 plays an obligatory role in the response of these cells. A distinct subpopulation of B cells which lack C3 receptors respond to T-independent antigens. The precursors of PFC for the ABA epitope reside largely or exclusively in the CRL(+) compartment in A/J mice, whereas precursors for the DNP determinant are found in both compartments.
Molecular Diagnosis of Primary Mediastinal B Cell Lymphoma Identifies a Clinically Favorable Subgroup of Diffuse Large B Cell Lymphoma Related to Hodgkin Lymphoma
Authors: Andreas Rosenwald, George Wright, Karen Leroy, Xin Yu, Philippe Gaulard, Randy D. Gascoyne, Wing C. Chan, Tong Zhao, Corinne Haioun, Timothy C. Greiner, Dennis D. Weisenburger, James C. Lynch, Julie Vose, James O. Armitage, Erlend B. Smeland, Stein Kvaloy, Harald Holte, Jan Delabie, Elias Campo, Emili Montserrat, Armando Lopez-Guillermo, German Ott, H. Konrad Muller-Hermelink, Joseph M. Connors, Rita Braziel, Thomas M. Grogan, Richard I. Fisher, Thomas P. Miller, Michael LeBlanc, Michael Chiorazzi, Hong Zhao, Liming Yang, John Powell, Wyndham H. Wilson, Elaine S. Jaffe, Richard Simon, Richard D. Klausner, Louis M. Staudt
Journal: The Journal of Experimental Medicine (2003)

Using current diagnostic criteria, primary mediastinal B cell lymphoma (PMBL) cannot be distinguished from other types of diffuse large B cell lymphoma (DLBCL) reliably. We used gene expression profiling to develop a more precise molecular diagnosis of PMBL. PMBL patients were considerably younger than other DLBCL patients, and their lymphomas frequently involved other thoracic structures but not extrathoracic sites typical of other DLBCLs. PMBL patients had a relatively favorable clinical outcome, with a 5-yr survival rate of 64% compared with 46% for other DLBCL patients. Gene expression profiling strongly supported a relationship between PMBL and Hodgkin lymphoma: over one third of the genes that were more highly expressed in PMBL than in other DLBCLs were also characteristically expressed in Hodgkin lymphoma cells. PDL2, which encodes a regulator of T cell activation, was the gene that best discriminated PMBL from other DLBCLs and was also highly expressed in Hodgkin lymphoma cells. The genomic loci for PDL2 and several neighboring genes were amplified in over half of the PMBLs and in Hodgkin lymphoma cell lines. The molecular diagnosis of PMBL should significantly aid in the development of therapies tailored to this clinically and pathogenetically distinctive subgroup of DLBCL.
Tumour necrosis factor-alpha production in human alveolar macrophages: modulation by inhaled corticosteroid
Authors: B.G. Marshall, A. Wangoo, L.I. Harrison, D.b Young, R.j Shaw
Journal: European Respiratory Journal (2000)

Gene transfer of tyrosine hydroxylase (TH) in animal models of Parkinson’s disease (PD), using either genetically modified cells or recombinant virus vectors, has produced partial restoration of behavioral and biochemical deficits. The limited success of this approach may be related to the availability of the cofactor, tetrahydrobiopterin (BH<sub>4</sub>), because neither the dopamine-depleted striatum nor the cells used for gene transfer possess a sufficient amount of BH<sub>4</sub> to support TH activity. To determine the role of BH<sub>4</sub> in gene therapy, fibroblast cells transduced with the gene for TH were additionally modified with the gene for GTP cyclohydrolase I, an enzyme critical for BH<sub>4</sub> synthesis. In contrast to cells transduced with only TH, doubly transduced fibroblasts spontaneously produced both BH<sub>4</sub> and 3,4-dihydroxy-l-phenylalanine. To examine further the importance of GTP cyclohydrolase I in gene therapy for PD, <i>in vivo</i> microdialysis was used to assess the biochemical changes in the dopamine-denervated striatum containing grafts of genetically modified fibroblasts. Only denervated striata grafted with fibroblasts possessing both TH and GTP cyclohydrolase I genes displayed biochemical restoration. However, no significant differences from controls were observed in apomorphine-induced rotation. This is partly attributable to a limited duration of gene expression <i>in vivo</i>. These differences between fibroblasts transduced with TH alone and those additionally modified with the GTP cyclohydrolase I gene indicate that BH<sub>4</sub> is critical for biochemical restoration in a rat model of PD and that GTP cyclohydrolase I is sufficient for production of BH<sub>4</sub>.
Chronic subdural haematoma, an unusual injury from playing basketball.
Authors: T M Keller, M C Holland
Journal: British Journal of Sports Medicine (1998)

Although the literature records instances of acute epidural haematoma and acute subdural haematoma related to playing basketball, there has not been a report of chronic subdural haematoma as a basketball injury. With the burgeoning interest in this sport in the United Kingdom and Europe, the possibility of this particular neurotrauma increases. Such an injury, along with the diagnosis and management of this often insidious lesion, is documented in this case report.
Respiratory viruses associated with community-acquired pneumonia in children: matched case–control study
Authors: Samuel Rhedin, Ann Lindstrand, Annie Hjelmgren, Malin Ryd-Rinder, Lars Öhrmalm, Thomas Tolfvenstam, Åke Örtqvist, Maria Rotzén-Östlund, Benita Zweygberg-Wirgart, Birgitta Henriques-Normark, Kristina Broliden, Pontus Naucler
Journal: Thorax (2015)

<h3>Background</h3> Community-acquired pneumonia (CAP) is the leading cause of death in children worldwide and a substantial proportion of childhood CAP is caused by viruses. A better understanding of the role of virus infections in this condition is needed to improve clinical management and preventive measures. The aim of the study was therefore to assess the association between specific respiratory viruses and childhood CAP. <h3>Methods</h3> A case–control study was conducted during 3 years in Stockholm, Sweden. Cases were children aged ≤5 years with radiological CAP. Healthy controls were consecutively enrolled at child health units during routine visits and matched to cases on age and calendar time. Nasopharyngeal aspirates were obtained and analysed by real-time PCR for 15 viruses. Multivariate conditional logistic regression was used to account for coinfections with other viruses and baseline characteristics. <h3>Results</h3> A total of 121 cases, of which 93 cases met the WHO criteria for radiological pneumonia, and 240 controls were included in the study. Viruses were detected in 81% of the cases (n=98) and 56% of the controls (n=134). Influenza virus, metapneumovirus and respiratory syncytial virus were detected in 60% of cases and were significantly associated with CAP with ORs &gt;10. There was no association with parainfluenza virus, human enterovirus or rhinovirus and coronavirus and bocavirus were negatively associated with CAP. <h3>Conclusions</h3> Our study indicates viral CAP is an underestimated disease and points out hMPV as a new important target for the prevention of childhood CAP.
View from Scottish pilot site of Safer Patients Initiative
Authors: P. O'Connor
Journal: BMJ (2011)

As a lead clinician in NHS Tayside’s team in the Safer Patients Initiative (SPI1) and a faculty member in SPI2, I find it difficult to reconcile the results in Benning and colleagues’ evaluation with my experience and local data.1 NHS Tayside achieved a 63% reduction in adverse events in SPI1 by means of the global trigger tool, and the trigger …
A 12-Gene Set Predicts Survival Benefits from Adjuvant Chemotherapy in Non–Small Cell Lung Cancer Patients
Authors: Hao Tang, Guanghua Xiao, Carmen Behrens, Joan Schiller, Jeffrey Allen, Chi-Wan Chow, Milind Suraokar, Alejandro Corvalan, Jianhua Mao, Michael A. White, Ignacio I. Wistuba, John D. Minna, Yang Xie
Journal: Clinical Cancer Research (2013)

Prospectively identifying who will benefit from adjuvant chemotherapy (ACT) would improve clinical decisions for non-small cell lung cancer (NSCLC) patients. In this study, we aim to develop and validate a functional gene set that predicts the clinical benefits of ACT in NSCLC.An 18-hub-gene prognosis signature was developed through a systems biology approach, and its prognostic value was evaluated in six independent cohorts. The 18-hub-gene set was then integrated with genome-wide functional (RNAi) data and genetic aberration data to derive a 12-gene predictive signature for ACT benefits in NSCLC.Using a cohort of 442 stage I to III NSCLC patients who underwent surgical resection, we identified an 18-hub-gene set that robustly predicted the prognosis of patients with adenocarcinoma in all validation datasets across four microarray platforms. The hub genes, identified through a purely data-driven approach, have significant biological implications in tumor pathogenesis, including NKX2-1, Aurora Kinase A, PRC1, CDKN3, MBIP, and RRM2. The 12-gene predictive signature was successfully validated in two independent datasets (n = 90 and 176). The predicted benefit group showed significant improvement in survival after ACT (UT Lung SPORE data: HR = 0.34, P = 0.017; JBR.10 clinical trial data: HR = 0.36, P = 0.038), whereas the predicted nonbenefit group showed no survival benefit for 2 datasets (HR = 0.80, P = 0.70; HR = 0.91, P = 0.82).This is the first study to integrate genetic aberration, genome-wide RNAi data, and mRNA expression data to identify a functional gene set that predicts which resectable patients with non-small cell lung cancer will have a survival benefit with ACT.
Paraplegia secondary to fracture-subluxation of the thoracic spine sustained playing rugby union football
Authors: A J Walsh, S Shine, F McManus
Journal: British Journal of Sports Medicine (2004)

Fractures of the spinal column during rugby matches of all codes are rare but catastrophic, especially when associated with spinal cord injury. The cervical spine is vulnerable during trauma to the head and neck in contact sports. Spinal injuries reported during rugby matches have almost exclusively involved the cervical region, often with neurological sequelae. This is the first reported case of paraplegia caused by a fracture-dislocation of the thoracic spine resulting from a low velocity rugby union injury.
Kinetics of the Establishment of Human Peripheral Blood Cultures&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: C. Rosenfeld, A. Macieira-Coelho, A. M. Venuat, C. Jasmin, T. Q. Tuan
Journal: JNCI Journal of the National Cancer Institute (1969)

Cultures were started with human normal and leukemic peripheral blood cells. Cells were counted from the time of inoculation until the cultures were well established in vitro. Five lines were established from leukemic blood. The comparison between the curves representing cumulative growth, the ratio between the number of cells after 3 or 4 days of growth and the respective inoculum, the cell doubling time, and the morphology revealed an intermediary population that seemed to adapt in vitro after a variable time. This population was characterized by the heterogeneity found among the different parameters analyzed. Later, the cell population became more homogeneous. Results support the hypothesis that the established population originated in culture. The different theories concerning establishment in vitro are discussed.
Monofunctional Platinum–DNA Adducts Are Strong Inhibitors of Transcription and Substrates for Nucleotide Excision Repair in Live Mammalian Cells
Authors: Guangyu Zhu, MyatNoeZin Myint, Wee Han Ang, Lina Song, Stephen J. Lippard
Journal: Cancer Research (2011)

To overcome drug resistance and reduce the side effects of cisplatin, a widely used antineoplastic agent, major efforts have been made to develop next generation platinum-based anticancer drugs. Because cisplatin-DNA adducts block RNA polymerase II unless removed by transcription-coupled excision repair, compounds that react similarly but elude repair are desirable. The monofunctional platinum agent pyriplatin displays antitumor activity in mice, a cytotoxicity profile in cell cultures distinct from that of cisplatin, and a unique in vitro transcription inhibition mechanism. In this study, we incorporated pyriplatin globally or site specifically into luciferase reporter vectors to examine its transcription inhibition profiles in live mammalian cells. Monofunctional pyriplatin reacted with plasmid DNA as efficiently as bifunctional cisplatin and inhibited transcription as strongly as cisplatin in various mammalian cells. Using repair-defective nucleotide excision repair (NER)-, mismatch repair-, and single-strand break repair-deficient cells, we show that NER is mainly responsible for removal of pyriplatin-DNA adducts. These findings reveal that the mechanism by which pyriplatin generates its antitumor activity is very similar to that of cisplatin, despite the chemically different nature of their DNA adducts, further supporting a role for monofunctional platinum anticancer agents in human cancer therapy. This information also provides support for the validity of the proposed mechanism of action of cisplatin and provides a rational basis for the design of more potent platinum anticancer drug candidates using a monofunctional DNA-damaging strategy.
Asthma and Outdoor Air Pollution
Journal: Thorax (1996)

Lung disease induced by drug addictionIn their editorial on the pulmonary con- sequences ofillicit drug use (November 1995; 50:1125-7) Benson and Bentley draw at- tention to barotrauma as a complication of cocaine inhalation.Pneumothorax, pneumomediastinum, and pneumopericardium have also been described, however, in association with the use of marijuana,12 a drug that is more widely used in England and Australia than cocaine.The mechanism of injury is thought to be by coughing while breath- holding in inspiration, or by performance of a Valsalva manoeuvre.The latter has been recognised as a cause of spontaneous pneumo- mediastinum since the 17th century.3We have found it rewarding to seek a history of illicit drug use in young adult patients presenting with spontaneous pneumothorax.
Biological therapy for paediatric IBD: effective but associated with financial and safety issues
Authors: F. L. Cameron, D. C. Wilson, M. Wilson, W. M. Bisset, A. Jamieson, N. Basheer, R. K. Russell
Journal: Gut (2011)

<h3>Introduction</h3> Biological agents are increasingly used as treatment for paediatric inflammatory bowel disease (IBD) in the UK, yet the evidence base is very limited and safety concerns are rising. We aimed to evaluate pattern of usage, effectiveness and safety in the clinical setting using a Scottish national framework. <h3>Methods</h3> Usage of the biological agents infliximab (IFX), adalimumab (ADA) and natalizumab (NAT) for treatment of paediatric IBD (aged &lt;18 years of age at start of biological therapy) from 1/1/00 to 30/04/10 was collated in a retrospective audit. Treatment was administered by members of the Scottish Society of Paediatric Gastroenterology, Hepatology and Nutrition (all regional academic paediatric centres and interested DGHs in Scotland). <h3>Results</h3> 112 children had 1 or more biological agent administered from a median (range) age of 14.3 (6.6–17.9) years; 50 (45%) were female and 102 (91%) had Crohn9s disease (CD), 8 (7%) had ulcerative colitis (UC) and 2 (2%) had inflammatory bowel disease unspecified (IBDU). Twenty-two (20%) had trials of 2 biological agents. 104 children (98 CD) had IFX, with a median (range) of 4 (1–25) infusions and almost all with moderate-severe IBD. 38 entered remission, 34 responded and 32 had no response. 11 of the 46 (24%) proceeding to maintenance IFX required escalation of therapy. 14 (13%) had infusion events with 3 having anaphylaxis and 7 reactions led to discontinuation. 1 child developed a lupus-like reaction requiring prolonged hospitalisation and 1 had severe infection, with no deaths. 19 (18%) proceeded to ADA. 23 children (all CD) had ADA therapy (including 19 after IFX, 2 as first biological and 2 with inflammatory arthritis in whom CD developed while on etanercept), with a median of 20 doses and nearly all with moderate-severe IBD. 11 entered remission, 6 responded and 6 had no response. All proceeded to maintenance and 11 (50%) required escalation of therapy. 13 had pain at injection site and none had reactions leading to discontinuation. 1 child developed leucopaenia and 1 had a severe viral infection, with no deaths. 2 children with CD had NAT, both in a trial, and both proceeded to IFX after the agent was withdrawn. <h3>Conclusion</h3> Our nationwide ‘real-life’ experience shows that biological agents are effective in moderate-severe paediatric IBD in the clinical setting, but there are significant financial issues (need for dose escalation or multiple biological usage), as well as safety issues.