tbuckley/cabot-search huggingface dataset:
Role of -511C>T/+3953C>T haplotypes of IL1B gene as risk factors of COPD
Authors: Tatyana Vlaykova, Dmo Dimov, Mateusz Kurzawski, Vanya Ilieva, Atanas Koychev, Gospodinka Prakova, Maya Gulubova, Vladimir Maximov, Marek Drozdzik, Vasil Dimitrov
Journal: European Respiratory Journal (2012)

COPD is multifactorial lung disease driven by abnormal inflammatory reaction. Therefore, inflammatory mediators are considered to be of distinct importance in pathogenesis of COPD. It is well recognized that the genetic factors play a role in susceptibility to COPD. Hence, polymorphisms in pro-inflammatory cytokines may confer a risk for the development of COPD. There are several case-control studies focused on the role of some of the described SNPs in  IL1B  in COPD, however no previous study has been conducted to evaluate the role of haplotypes of  -511C>T  and  +3953C>T  in  IL1B  as risk factors of COPD.  The aim of the current study was to investigated the role of the haplotypes of the -511C>T and +3953C>T in  IL1B  as candidate risk factors of COPD in Bulgarian population.  We genotyped 163 patients with COPD and 174 control individuals using Taqman genotyping assay for  IL1B  -511C>T  SNP and PCR-RFLP-based method for  +3953C>T  SNP.  The frequencies of the  IL1B  haplotypes of the studied two loci of  IL1B (-511C>T  and  +3953C>T ) did not differ significantly between controls and COPD patients (p=0.099). However, the T_C haplotype, constructed by alleles found to determine enhanced expression of IL-1β, appeared to be associated with higher risk of COPD (OR 1.25, 0.88-1.79, p=0.231) compared to the most common C_C haplotype and with 1.70-fold higher risk of COPD (95% CI, 1.10-2.64, p=0.018) compared to the C_T haplotype, previously associated with lower  IL1B  expression.  Based on the results of the current study for the first time we propose that the T_C haplotype of  IL1B -511C>T:+3953C>T, supposed to determine enhanced expression of IL-1b, is a predisposing factor for COPD in Bulgarian population.
High-Grade Pegylated Asparaginase-Related Hepatotoxicity Occurrence In a Pediatric-Inspired Adult Acute Lymphoblastic Leukemia Regimen Does Not Necessarily Predict Recurrent Hepatotoxicity In Subsequent Cycles
Authors: Patrick W. Burke, Ibrahim Aldoss, Matthew A. Lunning, Vassilios I. Avramis, Ann M. Mohrbacher, Vinod Pullarkat, Martin S. Tallman, Dan Douer
Journal: Blood (2013)
Minor Changes in Expression of the Mismatch Repair Protein MSH2 Exert a Major Impact on Glioblastoma Response to Temozolomide
Authors: José L. McFaline-Figueroa, Christian J. Braun, Monica Stanciu, Zachary D. Nagel, Patrizia Mazzucato, Dewakar Sangaraju, Edvinas Cerniauskas, Kelly Barford, Amanda Vargas, Yimin Chen, Natalia Tretyakova, Jacqueline A. Lees, Michael T. Hemann, Forest M. White, Leona D. Samson
Journal: Cancer Research (2015)

Glioblastoma (GBM) is often treated with the cytotoxic drug temozolomide, but the disease inevitably recurs in a drug-resistant form after initial treatment. Here, we report that in GBM cells, even a modest decrease in the mismatch repair (MMR) components MSH2 and MSH6 have profound effects on temozolomide sensitivity. RNAi-mediated attenuation of MSH2 and MSH6 showed that such modest decreases provided an unexpectedly strong mechanism of temozolomide resistance. In a mouse xenograft model of human GBM, small changes in MSH2 were sufficient to suppress temozolomide-induced tumor regression. Using The Cancer Genome Atlas to analyze mRNA expression patterns in tumors from temozolomide-treated GBM patients, we found that MSH2 transcripts in primary GBM could predict patient responses to initial temozolomide therapy. In recurrent disease, the absence of microsatellite instability (the standard marker for MMR deficiency) suggests a lack of involvement of MMR in the resistant phenotype of recurrent disease. However, more recent studies reveal that decreased MMR protein levels occur often in recurrent GBM. In accordance with our findings, these reported decreases may constitute a mechanism by which GBM evades temozolomide sensitivity while maintaining microsatellite stability. Overall, our results highlight the powerful effects of MSH2 attenuation as a potent mediator of temozolomide resistance and argue that MMR activity offers a predictive marker for initial therapeutic response to temozolomide treatment.
Occupational cancer in europe
Authors: P Boffetta, M Kogevinas
Journal: Environmental Health Perspectives (1999)

This monograph summarizes the current research on the epidemiology and prevention of occupational cancer in Europe. Eleven peer-reviewed articles offer a composite view of the current status and future perspectives of this discipline at a time of major economic and political changes in Europe. The monograph includes a brief history of occupational cancer research in Europe and the current burden of cancer from occupational exposure. A large portion of the monograph is devoted to reviews of occupational cancer in various European countries or groups of countries. The first two reviews describe those regions with the strongest tradition of research in the field: the Nordic countries and the United Kingdom. These countries are characterized by high-quality cancer registries and routinely collected information on occupation, e.g., on the occasion of censuses, allowing record linkage studies. Four articles address the situation in the remaining large Western European countries--France, Germany, Italy, and Spain. Although these countries have a strong tradition in occupational health research, with the possible exception of Spain, their epidemiologic research dates back only to the 1970s and 1980s; in recent years, however, research on occupational cancer has expanded considerably. The last two articles of the geographic overview describe the occupational cancer research in the Central European countries and the European territories of the Commonwealth of Independent States. The authors of these two articles critically review the available data on occupational cancer from former Socialist countries and provide reliable information on the extent and amount of occupational exposure to carcinogens. The two final articles of the monograph address specific thematic issues: the importance of asbestos as an occupational carcinogen in Europe and the use of routinely collected data to investigate occupational cancer in women, based on the experience in England and Wales. Despite the heterogeneity of these articles, which reflects to a large extent the differences in quality and completeness of the available data on occupational cancer, they represent an original attempt to provide a systematic overview of occupational cancer research in Europe. This publication is originally a partial result of two projects on occupational cancer in Europe funded by the European Commission, Directorate General XII (grants BMH1-CT92-1110 and BMH1-CT95-1100) and has been expanded to include non-European Union countries.
Randomized Phase II Study of Docetaxel Versus Doxorubicin in First- and Second-Line Chemotherapy for Locally Advanced or Metastatic Soft Tissue Sarcomas in Adults: A Study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group
Authors: Jaap Verweij, Siow Ming Lee, Wlodzimir Ruka, Jose Buesa, Robert Coleman, Rene van Hoessel, Caroline Seynaeve, Eugenio Donato di Paola, Martine van Glabbeke, D. Tonelli, Ian R. Judson
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To assess antitumor response and time to progression (TTP) with docetaxel compared with doxorubicin in first-line treatment of advanced and/or metastatic soft tissue sarcoma. PATIENTS AND METHODS: Patients with measurable soft tissue sarcoma lesions and adequate bone marrow, liver, and renal function were entered onto the study. They were randomized to either docetaxel 100 mg/m 2 given as a 1-hour intravenous infusion every 3 weeks or doxorubicin 75 mg/m 2 given as a bolus injection every 3 weeks. A maximum of seven cycles of treatment were scheduled. The study was designed as a randomized phase III study evaluating TTP by log-rank model. There was a clause for premature closure of the trial if fewer than five responses were observed among the first 25 assessable patients in the docetaxel treatment arm. RESULTS: Eighty-six patients were entered onto the study; 85 were assessable for toxicity and 83 for response. The rate of severe granulocytopenia was not significantly different between the two arms. Nausea (P = .001), vomiting (P &lt; .001), and stomatitis (P = .005) were more common with doxorubicin therapy, whereas neurotoxicity was more frequent with docetaxel treatment. The response rate to doxorubicin therapy was 30% (95% confidence interval, 17% to 46%), whereas no responses to docetaxel therapy were seen (P &lt; .001). In view of this, the trial was closed prematurely and the phase III study part was not conducted. CONCLUSION: Docetaxel is inactive in soft tissue sarcomas and cannot be recommended for further use in treatment of this disease.
A comparison of on-site versus remote physician follow up of directly observed preventive treatment (DOPT) for latent tuberculosis infection (LTBI) on completion rates
Authors: Hashem Bishara, Liora Ore, Najat Armaly, Daniel Weiler Ravell
Journal: European Respiratory Journal (2012)

Background:  Ethiopian immigrants (EI) at absorption centers treated for LTBI by DOPT, were followed on-site from 2005 - 2007 by a physician, to supposedly enhance compliance to therapy. This strategy could not be continued and between 2008-2010, patients were followed at a tuberculosis center (TBC) 60 Km. away, while DOPT was continued at the absorption center.   Objective:  To compare completion rates and cost of DOPT among EI when managed at their place of residence vs. management at a TBC.   Methodology:  A retrospective cohort analysis of 547 medical records for all EI at absorption centers in Zefat who had started DOPT for LTBI and were followed up at absorption centers (2005-2006, study group -SG), compared to patients followed up at a TBC (2008-2010, comparison group – CG). Free transportation to the TBC was provided for the CG.   Findings:  Altogether 495 EIs were included (263 in the SG and 232 in the CG group). Both groups had high completion rates (SG: 96.2% vs. CG: 93.1%, p=0.14). While demographic factors did not predict treatment completion side effects were significantly associated with non-completion. Costs were the same for both groups.   Conclusion:  The success and cost of DOPT was not dependent on on-site physician involvement. High completion rates could be due to the congregation of immigrants in absorption centers leading to easy access to dedicated and skilled TB nursing staff.  Sponsored by the Israel National Institute for Health Policy Research and the Israel Lung and Tuberculosis Association.  Part of a Thesis submitted for MPH degree, School of Public Health, University of Haifa, Israel.
Effect of granulocyte-macrophage colony-stimulating factor on oral mucositis in head and neck cancer patients after cisplatin, fluorouracil, and leucovorin chemotherapy.
Authors: K H Chi, C H Chen, W K Chan, K C Chow, S Y Chen, S H Yen, J Y Chao, C Y Chang, K Y Chen
Journal: Journal of Clinical Oncology (1995)

PURPOSE To evaluate prospectively the efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the reduction of chemotherapy-induced oral mucositis. PATIENTS AND METHODS Twenty patients with stage IV squamous cell carcinoma of head and neck were studied. Two-cycles (periods) of identical doses of cisplatin, fluorouracil (5-FU), and leucovorin (PFL) chemotherapy with cisplatin 20 mg/m2/d, 5-FU 800 mg/m2/d, leucovorin 90 mg/m2/d by 96-hour continuous intravenous infusion every 3 weeks were given to each patient. After PFL chemotherapy, GM-CSF 4 micrograms/kg subcutaneously from days 5 to 14 or no therapy was given by a randomized self-controlled crossover study design. Oral mucositis was graded with modified Radiation Therapy Oncology Group criteria. RESULTS In the first cycle of PFL chemotherapy, GM-CSF significantly reduced the incidence, mean duration, and mean area under the curve (AUC) of severe oral gross mucositis (grade &gt; or = 3) compared with no therapy. These beneficial effects continued into the second cycle of PFL chemotherapy after crossover to no GM-CSF. The incidence of severe mucositis was reduced when GM-CSF was given in the second cycle of PFL. Analysis of variance indicated significant direct GM-CSF treatment effects on the mean AUC of gross/functional scores and duration of moderate gross mucositis (grade &gt; or = 2) over both periods. There was a significant period effect in favor of giving GM-CSF in the first cycle of chemotherapy. CONCLUSION GM-CSF can significantly reduce the severity and duration of chemotherapy-induced oral mucositis after PFL chemotherapy.
Methadone in cancer pain management: individualize dose and titrate to effect.
Authors: K M Foley, R W Houde
Journal: Journal of Clinical Oncology (1998)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1998.16.10.3213 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 9779693 Methadone in cancer pain management: individualize dose and titrate to effect. K M FoleyxK M FoleySearch for articles by this author , R W HoudexR W HoudeSearch for articles by this author https://doi.org/10.1200/JCO.1998.16.10.3213 First Page PDF © 1998 by American Society of Clinical Oncology
Neonatal resuscitation at the community level
Authors: Nitin Bhandari, Ram Bhandari, Poonam Kandel, Sudesh Sharma
Journal: European Respiratory Journal (2011)

Introduction:  Community Based New Born Care Program (CB-NCP) was piloted in Nepal in order to reach the MDG 4 target, which focuses on decreasing the perinatal mortality. The program focuses the community level and reaches the local doctors, community level health workers and volunteers, educates and trains them with major emphasis to correctly identify and manage birth asphyxia by the use of DeLee suction and bag and mask ventilation.   Aims:  The aim of this study was to assess the knowledge and proficiency gained by the community level (VHW/MCHW, FCHV) and health facility level health workers who participated in a Community Based New Born Care training program.   Methods:  Based on CB-NCP curriculum designed by the Child Health Division, two sets of checklists were developed for all levels.The knowledge of the 57 health facility staffs including doctors, 36 VHW/MCHW and 141 FCHV were collected through semi-structure questionnaire and the skill was assessed through the observational checklist with practical hands on bag and mask ventilation in a neonatal manikin.   Results:  The knowledge of health workers, VHW/MCHW and FCHV regarding the management of birth asphyxiated baby was 100% (N=57/57), 94% (N=34/36) and 90.8% (N=128/141) respectively. The knowledge of FCHV regarding the management of asphyxiated new born was comparatively less than Health Worker and VHW/MCHW. Similarly, 49.1% (N=28/57) health workers, 50% (N=18/36) VHW/MCHW and 35.5% (N=50/141) FCHV correctly demonstrated the skills of management of asphyxiated newborn.   Conclusions:  Further studies are required to finally confirm the effectiveness of the intervention at the community level before implementing the program in other districts.
The c-jun N-terminal kinase signaling pathway regulates airway smooth muscle cell proliferation
Authors: Sahoko Chiba, Yuki Sumi, Kaori Okayasu, Tsukasa Okamoto, Tomoya Tateishi, Haruhiko Furusawa, Kimitake Tsuchiya, Toshihide Fujie, Meiyo Tamaoka, Hiroyuki Sakashita, Yasunari Miyazaki, Naohiko Inase
Journal: European Respiratory Journal (2014)

Background:  Airway smooth muscle cell (ASMC) proliferation is a central feature of asthmatic airways and is elicited by mechanisms of considerable interest. The role of the phosphoinositide 3-kinase (PI3K) and the extracellular signal-regulated kinase (ERK) pathway in ASMC proliferation is well established, but it remains unclear how the c-jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) pathways contribute. Nuclear factor-kappa B (NF-kB) plays a well-recognized role in airway inflammation such as asthma, but there are still open questions about its role in ASMC proliferation.   Objective:  We sought to determine the roles of JNK, p38, and NF-kB in ASMC proliferation.   Methods:  Normal human bronchial airway smooth muscle cells (BSMCs), asthmatic human bronchial airway smooth muscle cells (DBSMC-Ass), and rat airway smooth muscle cells (rat ASMCs) were cultured  in vitro . The effect of JNK, p38, or NF-kB inhibition on ASMC proliferation in response to fetal bovine serum (FBS) was estimated by crystal violet assay and tritiated thymidine uptake. The involvement of cell cycle regulators was examined using real-time quantitative PCR and Western blotting.   Results:  The inhibition of JNK by both chemical inhibitor and small interfering RNA (siRNA) strongly suppressed FBS-induced proliferation in BSMCs, DBSMC-Ass, and rat ASMCs. The p38 and NF-kB inhibitors, however, had little effect. The JNK inhibitor significantly decreased cyclin D1 protein levels in human ASMCs without significantly changing the level of cyclin D1 mRNA.   Conclusion:  The JNK pathway contributes to FBS-induced human ASMC proliferation, at least in part, via the regulation of cyclin D1.
Determinants of support for pictorial warning labels on packaging of tobacco products: An analysis of 26,566 adults in 27 EU countries
Authors: Israel Agaku, Constantine Vardavas
Journal: European Respiratory Journal (2014)

Introduction:  The revised EU Tobacco Products Directive (TPD) in 2014 stresses the need to update the current status quo in tobacco product labelling. We hence aimed to assess the determinants of population support for pictorial warning labels on tobacco products throughout the EU.   Methods: A secondary analysis of the Special Eurobarometer 385 (77.1) survey was performed. In total 26,566 adults, ≥15 years of age, from 27 countries in the European Union (EU) responded. The study was IRB exempt: IRB14-0346.   Results:  Approximately 80.3% of all EU adults supported pictorial health warnings on all tobacco products. Support was significantly lower among current cigarette smokers (adjusted odds ratio [aOR] = 0.27; 95%CI: 0.24-0.30) and among respondents in urban areas. In contrast, support was significantly higher among females (aOR = 1.17; 95%CI: 1.06-1.30). By region, the likelihood of support for pictorial health warnings on all tobacco products was significantly higher among respondents in Southern (aOR = 1.40; 95%CI: 1.22-1.61); Northern (aOR = 1.25; 95%CI: 1.10-1.43); and Eastern Europe (aOR = 1.48; 95%CI: 1.29-1.70) compared to those in Western Europe. No significant differences in support for pictorial warnings on all tobacco products were observed by socio-economic status, or age.   Conclusions:  The above analyses indicate significant population support for pictorial warning labels within the EU, however geographical differences in support were noted. These findings strengthen the need for the revised EU-TPD to update existing tobacco product packaging based also on population request.
Prognostic factors for survival in advanced non-small-cell lung cancer: univariate and multivariate analyses including recursive partitioning and amalgamation algorithms in 1,052 patients. The European Lung Cancer Working Party.
Authors: M Paesmans, J P Sculier, P Libert, G Bureau, G Dabouis, J Thiriaux, J Michel, O Van Cutsem, R Sergysels, P Mommen
Journal: Journal of Clinical Oncology (1995)

This study attempted to determine the prognostic value for survival of various pretreatment characteristics in patients with nonresectable non-small-cell lung cancer in the context of more than 10 years of experience of a European Cooperative Group.We included in the analysis all eligible patients (N = 1,052) with advanced non-small-cell lung cancer registered onto one of seven trials conducted by the European Lung Cancer Working Party (ELCWP) during one decade. The patients were treated by chemotherapy regimens based on platinum derivatives. We prospectively collected 23 variables and analyzed them by univariate and multivariate methods.The global estimated median survival time was 29 weeks, with a 95% confidence interval of 27 to 30 weeks. After univariate analysis, we applied two multivariate statistical techniques. In a Cox regression model, the selected explanatory variables were disease extent, Karnofsky performance status, WBC and neutrophil counts, metastatic involvement of skin, serum calcium level, age, and sex. These results were confirmed by application of recursive partitioning and amalgamation algorithms (RECPAM), which led to classification of the patients into four homogeneous subgroups.We confirmed by our analysis the role of well-known independent prognostic factors for survival, but also identified the effect of the neutrophil count, rarely studied, with the use of two methods: a classical Cox regression model and a RECPAM analysis. The classification of patients into the four subgroups we obtained needs to be validated in other series.
India’s Supreme Court allows girl who was raped to have termination outside legal limits
Authors: Sanjeet Bagcchi
Journal: BMJ (2015)

A medical panel constituted by India’s Supreme Court has allowed a 14 year old rape victim in Gujarat, who is said to be at 25 weeks of pregnancy, to have a termination. In India termination is not usually allowed after 20 weeks.

On 28 July the Supreme Court over-ruled an earlier decision by the High Court and said that the surgery could go ahead provided that gynaecologists and psychologists were in favour of the procedure.1

In February the girl visited a doctor with symptoms of typhoid. She was allegedly raped by the doctor and became pregnant. The Supreme Court’s bench of justices said that “it would direct the authorities …
Is Chronic Fatigue Syndrome Synonymous with Effort Syndrome?
Authors: S D Rosen, J C King, J B Wilkinson, P G F Nixon
Journal: Journal of the Royal Society of Medicine (1990)

Chronic fatigue syndrome (CFS), including myalgic encephalomyelitis (ME) and postviral syndrome (PVS), is a term used today to describe a condition of incapacity for making and sustaining effort, associated with a wide range of symptoms. None of the reviews of CFS has provided a proper consideration of the effort syndrome caused by chronic habitual hyperventilation. In 100 consecutive patients, whose CFS had been attributed to ME or PVS, the time course of their illness and the respiratory psychophysiological studies were characteristic of chronic habitual hyperventilation in 93. It is suggested that the labels ‘CFS’, ‘ME’ or TVS' should be withheld until chronic habitual hyperventilation - for which conventional rehabilitation is available - has been definitively excluded.
Influenza A Virus Infection, Innate Immunity, and Childhood
Authors: Bria M. Coates, Kelly L. Staricha, Kristin M. Wiese, Karen M. Ridge
Journal: JAMA Pediatrics (2015)

Infection with influenza A virus is responsible for considerable morbidity and mortality in children worldwide. While it is apparent that adequate activation of the innate immune system is essential for pathogen clearance and host survival, an excessive inflammatory response to infection is detrimental to the young host. A review of the literature indicates that innate immune responses change throughout childhood. Whether these changes are genetically programmed or triggered by environmental cues is unknown. The objectives of this review are to summarize the role of innate immunity in influenza A virus infection in the young child and to highlight possible differences between children and adults that may make children more susceptible to severe influenza A infection. A better understanding of age-related differences in innate immune signaling will be essential to improve care for this high-risk population.