tbuckley/cabot-search huggingface dataset:
Upper-Room Ultraviolet Light and Negative Air Ionization to Prevent Tuberculosis Transmission
Authors: A. Roderick Escombe, David A. J Moore, Robert H Gilman, Marcos Navincopa, Eduardo Ticona, Bailey Mitchell, Catherine Noakes, Carlos Martínez, Patricia Sheen, Rocio Ramirez, Willi Quino, Armando Gonzalez, Jon S Friedland, Carlton A Evans
Journal: PLoS Medicine (2009)

Background Institutional tuberculosis (TB) transmission is an important public health problem highlighted by the HIV/AIDS pandemic and the emergence of multidrug- and extensively drug-resistant TB. Effective TB infection control measures are urgently needed. We evaluated the efficacy of upper-room ultraviolet (UV) lights and negative air ionization for preventing airborne TB transmission using a guinea pig air-sampling model to measure the TB infectiousness of ward air. Methods and Findings For 535 consecutive days, exhaust air from an HIV-TB ward in Lima, Perú, was passed through three guinea pig air-sampling enclosures each housing approximately 150 guinea pigs, using a 2-d cycle. On UV-off days, ward air passed in parallel through a control animal enclosure and a similar enclosure containing negative ionizers. On UV-on days, UV lights and mixing fans were turned on in the ward, and a third animal enclosure alone received ward air. TB infection in guinea pigs was defined by monthly tuberculin skin tests. All guinea pigs underwent autopsy to test for TB disease, defined by characteristic autopsy changes or by the culture of Mycobacterium tuberculosis from organs. 35% (106/304) of guinea pigs in the control group developed TB infection, and this was reduced to 14% (43/303) by ionizers, and to 9.5% (29/307) by UV lights (both p < 0.0001 compared with the control group). TB disease was confirmed in 8.6% (26/304) of control group animals, and this was reduced to 4.3% (13/303) by ionizers, and to 3.6% (11/307) by UV lights (both p < 0.03 compared with the control group). Time-to-event analysis demonstrated that TB infection was prevented by ionizers (log-rank 27; p < 0.0001) and by UV lights (log-rank 46; p < 0.0001). Time-to-event analysis also demonstrated that TB disease was prevented by ionizers (log-rank 3.7; p = 0.055) and by UV lights (log-rank 5.4; p = 0.02). An alternative analysis using an airborne infection model demonstrated that ionizers prevented 60% of TB infection and 51% of TB disease, and that UV lights prevented 70% of TB infection and 54% of TB disease. In all analysis strategies, UV lights tended to be more protective than ionizers. Conclusions Upper-room UV lights and negative air ionization each prevented most airborne TB transmission detectable by guinea pig air sampling. Provided there is adequate mixing of room air, upper-room UV light is an effective, low-cost intervention for use in TB infection control in high-risk clinical settings.
Exhaled Nitric Oxide
Authors: Andrew D. Smith, Jan O. Cowan, Karen P. Brassett, Sue Filsell, Chris McLachlan, Gabrielle Monti-Sheehan, G. Peter Herbison, D. Robin Taylor
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Rationale: The initial management of patients who present with persistent respiratory symptoms includes recognizing those with the potential to benefit from inhaled steroid therapy. To date, this has required undertaking a "trial of steroid" to identify responders. There is increasing evidence that steroid response is more likely in patients with eosinophilic airway inflammation, and this can be assessed indirectly using exhaled nitric oxide (FENO) measurements. Objectives: We aimed to assess the predictive accuracy of FENO to identify steroid response in 52 patients presenting with undiagnosed respiratory symptoms in a single-blind, fixed-sequence, placebo-controlled trial of inhaled fluticasone for 4 weeks. Methods: Comparisons of predictive accuracy were made between FENO and other conventional predictors: peak flows, spirometry, bronchodilator response, and airway hyperresponsiveness measured at baseline. "Steroid response" was defined as change in symptoms, peak flows, spirometry, or airway hyperresponsiveness to adenosine based on established guidelines and recommendations. Results: Steroid response was significantly greater in the highest FENO tertile (> 47 ppb) for each endpoint. This outcome was independent of the diagnostic label. The predictive values for FENO were significantly greater than for almost all other baseline predictors, with an optimum cut point of 47 ppb. Conclusions: FENO measurements greater than 47 ppb provide a means of predicting steroid response in patients with undiagnosed respiratory symptoms. Assessing airway inflammation is of more practical value than diagnostic labeling when considering the potential usefulness of inhaled antiinflammatory therapy.
Demonstration of diagnostic and prognostic benefits of an interstitial lung disease (ILD) multidisciplinary team meeting
Authors: Lisa Spencer, Seamus Grundy, Melanie Greaves, Paul Bishop, Annette Duck, Colm Leonard
Journal: European Respiratory Journal (2011)

Introduction:  Idiopathic pulmonary fibrosis (IPF), the commonest of the idiopathic interstitial pneumonias, is increasing in incidence/prevalence. Diagnosis can be challenging due to a number of interstitial lung disease with overlapping clinical, radiological or pathological features. Recent guidelines (British Thoracic Society) emphasise the need for multidisciplinary team-based diagnosis, but little published evidence is available to support this recommendation.   Methods:  161 consecutive patients discussed at the ILD MDT meeting at University Hospital of South Manchester were analysed.   Results:  In 69 of 161 cases the MDT agreed with the diagnosis of the referring physician. In 67 of 161 cases a single ILD label different to that of the referring centre was given, and in 25 of 161 cases the ILD delivered a differential diagnosis only. Of 67 patients referred with definite IPF only 40 patients (60%) kept their label of IPF, the remaining 27 patients receiving a different diagnosis, predominantly non-specific interstitial pneumonitis (NSIP). At time of follow (3-6 years after MDT discussion) 52% of patients who kept their IPF diagnosis were alive versus 78% of patients alive where a pre-MDT diagnosis of IPF was changed to a more favourable diagnosis, p   Conclusion:  This data is the largest ILD MDT cohort thus far reported and is the first report to clearly link an MDT-based change in diagnosis from IPF to NSIP translating into documented improved survival.
Comparative Effects of Three Cytokine Regimens After High-Dose Cyclophosphamide: Granulocyte Colony-Stimulating Factor, Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF), and Sequential Interleukin-3 and GM-CSF
Authors: Alberto Ballestrero, Fabio Ferrando, Anna Garuti, Palma Basta, Roberta Gonella, Paola Stura, Giuseppe Sandro Mela, Mario Sessarego, Marco Gobbi, Franco Patrone
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To compare the toxicity and effects on hematologic recovery and circulating progenitor cell mobilization of three cytokine regimens administered after high-dose cyclophosphamide (HD-CTX; 6 g/m 2 ), given as the first step of a high-dose sequential chemotherapy. PATIENTS AND METHODS: Forty-eight patients with breast cancer or non-Hodgkin's lymphoma were randomized to receive granulocyte colony-stimulating factor (G-CSF) alone (arm 1), granulocyte-macrophage colony-stimulating factor (GM-CSF) alone (arm 2), or sequential interleukin-3 (IL-3) and GM-CSF (arm 3). Cytokines were administered as a single daily subcutaneous injection at a dose of 5 to 6 μg/kg/d. Progenitor cells were evaluated in peripheral blood as well as in apheretic product as both CD34 + cells and granulocyte-macrophage colony-forming units (CFU-GM). RESULTS: Neutrophil recovery was faster in arm 1 as compared with arms 2 and 3 (P &lt; .0001); no significant differences were observed between arms 2 and 3. In arm 3, a moderate acceleration of platelet recovery was observed, but it was statistically significant only as compared with arm 1 (P = .028). The peak of CD34 + cells was hastened in a median of 2 days in arm 1 compared with arms 2 and 3 (P = .0002), whereas the median peak value of CD34 + cells and CFU-GM was similar in the three patient groups. Administration of IL-3 and GM-CSF resulted in more significant toxicity requiring pharmacologic treatment in 90% of patients. CONCLUSION: The three cytokine regimens administered after HD-CTX are comparably effective in reducing hematologic toxicity and mobilizing the hematopoietic progenitor cells. G-CSF accelerates leukocyte recovery and progenitor mobilization. Although G-CSF–treated patients have somewhat slower platelet recovery, they definitely have fewer side effects.
A multicentre study of percentage change in venous leg ulcer area as a prognostic index of healing at 24 weeks
Authors: T. Gilman
Journal: British Journal of Dermatology (2003)

Journal Article A multicentre study of percentage change in venous leg ulcer area as a prognostic index of healing at 24 weeks Get access T. Gilman T. Gilman Hollister Incorporated, Libertyville, IL 60048‐3746, U.S.A. E‐mail: tom.gilman@hollister.com Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 149, Issue 4, 1 October 2003, Pages 896–897, https://doi.org/10.1046/j.1365-2133.2003.05575.x Published: 01 October 2003
Epidermal Growth Factor Receptor Gene Polymorphisms Predict Pelvic Recurrence in Patients with Rectal Cancer Treated with Chemoradiation
Authors: Wu Zhang, David J. Park, Bo Lu, Dong Yun Yang, Michael Gordon, Susan Groshen, Jim Yun, Oliver A. Press, Daniel Vallböhmer, Katrin Rhodes, Heinz-Josef Lenz
Journal: Clinical Cancer Research (2005)

An association between epidermal growth factor receptor (EGFR) signaling pathway and response of cancer cells to ionizing radiation has been reported. Recently, a polymorphic variant in the EGFR gene that leads to an arginine-to-lysine substitution in the extracellular domain at codon 497 within subdomain IV of EGFR has been identified. The variant EGFR (HER-1 497K) may lead to attenuation in ligand binding, growth stimulation, tyrosine kinase activation, and induction of proto-oncogenes myc, fos, and jun. A (CA)(n) repeat polymorphism in intron 1 of the EGFR gene that alters EGFR expression in vitro and in vivo has also been described. In the current pilot study, we assessed both polymorphisms in 59 patients with locally advanced rectal cancer treated with adjuvant or neoadjuvant chemoradiation therapy using PCR-RFLP and a 5'-end [gamma-(33)P]ATP-labeled PCR protocol. We tested whether either polymorphism alone or in combination can be associated with local recurrence in the setting of chemoradiation treatment. We found that patients with HER-1 497 Arg/Arg genotype or lower number of CA repeats (both alleles <20) tended to have a higher risk of local recurrence (P = 0.24 and 0.31, respectively). Combined analysis showed the highest risk for local recurrence was seen in patients who possessed both a HER-1 497 Arg allele and <20 CA repeats (P = 0.05, log-rank test). Our data suggest that the HER-1 R497K and EGFR intron 1 (CA)(n) repeat polymorphisms may be potential indicators of radiosensitivity in patients with rectal cancer treated with chemoradiation.
Routine Adrenalectomy in Patients with Locally Advanced Renal Cell Cancer Does Not Offer Oncologic Benefit and Places a Significant Portion of Patients at Risk for an Asynchronous Metastasis in a Solitary Adrenal Gland
Authors: Christopher J. Weight, Simon P. Kim, Christine M. Lohse, John C. Cheville, R. Houston Thompson, Stephen A. Boorjian, Bradley C. Leibovich
Journal: European Urology (2011)
Detection of Aberrant Methylation of Four Genes in Plasma DNA for the Detection of Breast Cancer
Authors: Mohammad O. Hoque, Qinghua Feng, Papa Toure, Amadou Dem, Cathy W. Critchlow, Stephen E. Hawes, Troy Wood, Carmen Jeronimo, Eli Rosenbaum, Joshua Stern, Mujun Yu, Barry Trink, Nancy B. Kiviat, David Sidransky
Journal: Journal of Clinical Oncology (2006)

Novel approaches to breast cancer screening are necessary, especially in the developing world where mammography is not feasible. In this study, we explored the hypothesis that blood-based biomarkers have potential for biomarkers for breast cancer.We first determined the frequency of aberrant methylation of four candidate genes (APC, GSTP1, Rassf1A, and RARbeta2) in primary breast cancer tissues from West African women with predominantly advanced cancers. We used a high-throughput DNA methylation assay (quantitative methylation-specific polymerase chain reaction) to examine plasma from 93 women with breast cancer and 76 controls for the presence of four methylated genes. Samples were randomly divided evenly into training and validation data sets. Cutoff values for gene positivity of the plasma-based assay and the gene panel were determined by receiver operating characteristic curves in the training data set and subsequently evaluated as a screening tool in the validation data set.Methylation of at least one gene resulted in a sensitivity of 62% and a specificity of 87%. Moreover, the assay successfully detected 33% (eight of 24) of early-stage tumors.These data suggest that epigenetic markers in plasma may be of interest for detection of breast cancer. Identification of additional breast cancer specific methylated genes with higher prevalence in early stage cancers would improve this approach.
Lyn, a Src family kinase, regulates activation of epidermal growth factor receptors in lung adenocarcinoma cells
Authors: Parnetta Sutton, Jeffrey A Borgia, Philip Bonomi, Janet MD Plate
Journal: Molecular Cancer (2013)

Abstract Background Activation of receptors for growth factors on lung epithelial cells is essential for transformation into tumor cells, supporting their viability and proliferation. In most lung cancer patients, EGFR is constitutively activated without evidence of mutation. Defining mechanisms for constitutive activation of EGFR could elucidate additional targets for therapy of lung cancers. Methods The approach was to identify lung cancer cell lines with constitutively activated EGFR and use systematic selection of inhibitors to evaluate their effects on specific EGFR phosphorylations and downstream signaling pathways. Interactions between receptors, kinases, and scaffolding proteins were investigated by co-immunoprecipitation plus Western blotting. Results The results revealed a dependence on Src family of tyrosine kinases for downstream signaling and cell growth. Lyn, a Src family kinase functional in normal and malignant B-lymphocytes, was a defining signal transducer required for EGFR signaling in Calu3 cell line. Src family kinase activation in turn, was dependent on PKCßII. Lyn and PKC exist in membrane complexes of RACK1 and in association with EGFR which pairs with other receptor partners. Silencing of Lyn expression with interfering siRNA decreased EGFR activation and cell viability. Conclusions The importance of Src family kinases and PKCßII in the initiation of the EGFR signaling pathway in lung tumor cells was demonstrated. We conclude that phosphorylation of EGFR is mediated through PKCßII regulation of Lyn activation, and occurs in association with RACK1 and Cbp/PAG proteins. We suggest that protein complexes in cell membranes, including lipid rafts, may serve as novel targets for combination therapies with EGFR and Src Family Kinase inhibitors in lung cancer.
Studies of T- and B-Lymphocytes in Patients with Connective Tissue Diseases
Authors: Ralph C. Williams, James R. DeBoard, Ove J. Mellbye, Ronald P. Messner, Folke D. Lindström
Journal: Journal of Clinical Investigation (1973)

Peripheral blood lymphocytes from normal subjects as well as patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and active tuberculosis were studied for the relative distribution of bone marrow-derived lymphocytes (B-cells) and thymic-derived T-cells. B-cells were identified by direct immunofluorescence of surface Ig markers; T-cells were studied using rabbit antisera to pooled human fetal thymocytes absorbed with chronic lymphatic leukemia lymphocytes as a source of B-cells. In normal subjects, the sum of percentages of peripheral blood lymphocytes staining for surface Ig (B-cells) plus the percentage of cells staining with the absorbed antithymocyte antiserum closely approximated 100%. The mean value for percent B-cells among 51 normals tested was 22.9%±7.1; mean T-cells value was 75.3±13.95%. T-cell-specific antiserum stained 18% of normal human bone marrow lymphocytes, 42.5% of lymphocytes from normal spleens, and 98% of cells obtained from thoracic duct drainage of patients with RA. Specificity of antihuman thymocyte antiserum appeared to depend on the use of living cells.
BAL findings in idiopathic nonspecific interstitial pneumonia and usual interstitial pneumonia
Authors: S. Veeraraghavan, P.I. Latsi, A.U. Wells, P. Pantelidis, A.G. Nicholson, T.V. Colby, P.L. Haslam, E.A. Renzoni, R.M. du Bois
Journal: European Respiratory Journal (2003)

Idiopathic pulmonary fibrosis (IPF), which has the histological pattern of usual interstitial pneumonia (UIP), is a progressive interstitial lung disease with a poor prognosis. Idiopathic interstitial pneumonias with a histological pattern of nonspecific interstitial pneumonia (NSIP) have a better prognosis than UIP, and may present with a clinical picture identical to IPF. The authors hypothesised that bronchoalveolar lavage (BAL) findings may distinguish between UIP and NSIP, and have prognostic value within disease subgroups. BAL findings were studied retrospectively in 54 patients with histologically proven (surgical biopsy) idiopathic UIP (n=35) or fibrotic NSIP (n=19), all presenting clinically as IPF. These findings were also compared with the BAL profile of patients with other categories of idiopathic interstitial pneumonias. BAL total and differential cell counts did not differ between the two groups. Survival was better in NSIP. In neither group were BAL findings predictive of survival or changes in lung function at 1 yr, even after adjustment for disease severity, smoking andtreatment. BAL differential counts in fibrotic NSIP differed from respiratory bronchiolitis-associated interstitial lung disease, but not from desquamative interstitial pneumonia or cellular NSIP. The authors conclude that bronchoalveolar lavage findings do not discriminate between usual interstitial pneumonia and nonspecific interstitial pneumonia in patients presenting with clinical features of idiopathic pulmonary fibrosis, and have no prognostic value, once the distinction between the two has been made histologically.
Nicotine Patch Therapy for Smoking Cessation Combined With Physician Advice and Nurse Follow-up
Authors: Richard D. Hurt
Journal: JAMA (1994)

To determine the efficacy of a 22-mg nicotine patch combined with the National Cancer Institute program for physician advice and nurse follow-up in providing withdrawal symptom relief, 1-year smoking cessation outcome, and percentage of nicotine replacement.Randomized, double-blind, placebo-controlled trial.Two-hundred forty healthy volunteers who were smoking at least 20 cigarettes per day.Based on the National Cancer Institute program, subjects received smoking cessation advice from a physician. Follow-up and relapse prevention were provided by a study nurse during individual counseling sessions. Subjects were randomly assigned to 8 weeks of a 22-mg nicotine or placebo patch.Abstinence from smoking was verified by expired air carbon monoxide levels. Withdrawal symptoms were recorded during patch therapy, and the percentage of nicotine replacement was calculated by dividing serum nicotine and cotinine levels at week 8 of patch therapy by levels obtained while smoking.Higher smoking cessation rates were observed in the active nicotine patch group at 8 weeks (46.7% vs 20%) (P < .001) and at 1 year (27.5% vs 14.2%) (P = .011). Higher smoking cessation rates were also observed in subjects assigned to the active patch who had lower serum levels of nicotine and cotinine at baseline, and withdrawal symptom relief was better in the active patch group compared with placebo.Clinically significant smoking cessation can be achieved using nicotine patch therapy combined with physician intervention, nurse counseling, follow-up, and relapse prevention. Smokers with lower baseline nicotine and cotinine levels had better cessation rates, which provides indirect evidence that they had more adequate nicotine replacement with this fixed dose of transdermal nicotine than those smokers with higher baseline levels.
A retroviral mutagenesis screen identifies Cd74 as a common insertion site in murine B-lymphomas and reveals the existence of a novel IFNγ-inducible Cd74 isoform
Authors: Magdalena Pyrz, Bruce Wang, Matthias Wabl, Finn Skou Pedersen
Journal: Molecular Cancer (2010)

Abstract Background Insertional mutagenesis screens in the mouse are an acknowledged approach to identify genes involved in the pathogenesis of cancer. The potential of these screens to identify genes causally involved in tumorigenesis is not only limited to the murine host, but many of these genes have also been proven to be involved in the oncogenic process in man. Results Through an insertional mutagenesis screen applying murine leukemia viruses in mouse, we found that Cd74 was targeted by proviral insertion in tumors of B-cell origin. This locus encodes a protein playing crucial roles in antigen presentation and B-cell homeostasis, and its deregulation is often associated with cancer in man. The distribution of insertions within the Cd74 locus prompted the identification of an alternative transcript initiated in intron 1 of Cd74 encoding an N-terminally truncated Cd74 isoform in tissues from un-infected mice, and transcriptional activation assays revealed a positive effect on the novel intronic promoter by a formerly described intronic enhancer in the Cd74 locus. Furthermore, we show that the new Cd74 isoform is IFNγ inducible and that its expression is differentially regulated from the canonical Cd74 isoform at the transcriptional level. Conclusions We here identify Cd74 as a common insertion site in murine B-lymphomas and describe a novel IFNγ-inducible murine Cd74 isoform differentially regulated from the canonical isoform and expressed under the control of an intronic promoter. The distribution and orientation of proviral insertion sites within the Cd74 locus underscores the causal involvement of the isoforms in the murine B-lymphomagenic process.
England's health department agrees to independent review of standardised tobacco packaging
Authors: A. O'Dowd
Journal: BMJ (2013)

England may be a step closer to following other countries in introducing standardised packaging of tobacco products, after the government announced that it will take advice from a new independent review.

In a move likely to be seen as bowing to growing acceptance of the benefits of such a policy, the Department of Health announced on 28 November that it had commissioned an independent review of standardised packaging, which is due to report next spring.

The review, to be led by the paediatrician Cyril Chantler, will focus on the evidence that standardised packaging of tobacco products benefits public health, looking in particular at evidence from Australia, where such a policy was introduced a year ago.

The health department held a consultation on standardised packaging between April and August 2012,1 and in July this year it announced …