tbuckley/cabot-search huggingface dataset:
Risk of cancer from occupational exposure to ionising radiation: retrospective cohort study of workers in France, the United Kingdom, and the United States (INWORKS)
Authors: David B Richardson, Elisabeth Cardis, Robert D Daniels, Michael Gillies, Jacqueline A O’Hagan, Ghassan B Hamra, Richard Haylock, Dominique Laurier, Klervi Leuraud, Monika Moissonnier, Mary K Schubauer-Berigan, Isabelle Thierry-Chef, Ausrele Kesminiene
Journal: BMJ (2015)

<b>Study question</b> Is protracted exposure to low doses of ionising radiation associated with an increased risk of solid cancer? <b>Methods</b> In this cohort study, 308 297 workers in the nuclear industry from France, the United Kingdom, and the United States with detailed monitoring data for external exposure to ionising radiation were linked to death registries. Excess relative rate per Gy of radiation dose for mortality from cancer was estimated. Follow-up encompassed 8.2 million person years. Of 66 632 known deaths by the end of follow-up, 17 957 were due to solid cancers. <b>Study answer and limitations</b> Results suggest a linear increase in the rate of cancer with increasing radiation exposure. The average cumulative colon dose estimated among exposed workers was 20.9 mGy (median 4.1 mGy). The estimated rate of mortality from all cancers excluding leukaemia increased with cumulative dose by 48% per Gy (90% confidence interval 20% to 79%), lagged by 10 years. Similar associations were seen for mortality from all solid cancers (47% (18% to 79%)), and within each country. The estimated association over the dose range of 0-100 mGy was similar in magnitude to that obtained over the entire dose range but less precise. Smoking and occupational asbestos exposure are potential confounders; however, exclusion of deaths from lung cancer and pleural cancer did not affect the estimated association. Despite substantial efforts to characterise the performance of the radiation dosimeters used, the possibility of measurement error remains. <b>What this study adds</b> The study provides a direct estimate of the association between protracted low dose exposure to ionising radiation and solid cancer mortality. Although high dose rate exposures are thought to be more dangerous than low dose rate exposures, the risk per unit of radiation dose for cancer among radiation workers was similar to estimates derived from studies of Japanese atomic bomb survivors. Quantifying the cancer risks associated with protracted radiation exposures can help strengthen the foundation for radiation protection standards. <b>Funding, competing interests, data sharing</b> Support from the US Centers for Disease Control and Prevention; Ministry of Health, Labour and Welfare of Japan; Institut de Radioprotection et de Sûreté Nucléaire; AREVA; Electricité de France; US National Institute for Occupational Safety and Health; US Department of Energy; and Public Health England. Data are maintained and kept at the International Agency for Research on Cancer.
A decade of breast cancer clinical investigation: results as reported in the Program/Proceedings of the American Society of Clinical Oncology.
Authors: R T Chlebowski, L M Lillington
Journal: Journal of Clinical Oncology (1994)

PURPOSE To test the hypothesis that clinical research results have driven changes in recent breast cancer management recommendations. METHODS All breast cancer abstracts in the Program/Proceedings of the American Society of Clinical Oncology (ASCO) from 1984 to 1993 were prospectively reviewed in 31 areas and categorized by study type, study question, whether statistical significance was claimed, and whether the abstract was presented. RESULTS Of 1,372 abstracts, 54% reported on prospective clinical trials (PCTs) and 17% on randomized clinical trials (RCTs). The total number of published abstracts progressively increased (from 87 in 1984 to 221 in 1993) and author citations nearly quadrupled (from 430 in 1984 to 1,642 in 1993, P &lt; .01); however, RCTs have come to represent a smaller proportion of reports: 37% (33 of 89) in 1986 versus 10% (22 of 221) in 1993 (P &lt; .001). The size of adjuvant-therapy RCTs has progressively increased (mean +/- SEM subjects/trial, 237 +/- 43 in 1984 to 874 +/- 374 in 1993), but has remained small in advanced-disease RCTs (mean +/- SEM subjects/trial, 145 +/- 25 in 1984 to 146 +/- 34 in 1993). For adjuvant therapy, 14 of 90 RCTs (with 51,207 patients) reported a significant (P &lt; .05) survival benefit for investigational therapies (16%). For advanced-disease therapy, only three of 141 RCTs (with 26,281 patients) reported a significant (P &lt; .05) survival benefit for investigational therapies (2%). Randomization was rarely used in trials of dose-intensity with blood-product support (zero of 86 trials) or locally advanced disease. CONCLUSION For breast cancer ASCO abstracts in the past decade, we determined the following: (1) adjuvant trials have not infrequently supported study hypotheses; and (2) advanced-disease trials have consistently failed to identify new approaches with a significant impact on survival. These results suggest that a critical process evaluation of current policy and procedures involved in directing breast cancer research is warranted, especially for strategies in advanced disease.
COPD: Acute exacerbation (AE) and hospitalization rate (HR) in patients with different serum surfactant protein D (SPD) level
Authors: Tetyana Pertseva, Kateryna Gashynova, Olena Bratus, Natalya Petrik
Journal: European Respiratory Journal (2012)

Aim 

To evaluate whether and in which extent SPD have influence on the AE and hospitalization rate in patients with COPD.

Study population 

26 patients with stable COPD, GOLD stage II-IV, made the study sample.

Methods 

SPD was evaluated in serum by ELISA (Hycult Biotech, Netherlands) for all patients. AE (including AE, required systemic corticosteroids (SCS) and antibiotic (AB) prescription) and HR during 12 months were evaluated retrospectively by analysis of patient's medical documentation.

Results 

In accordance with SPD level all patients were divided on two groups: 12 patients with SPD < 600 ng/ml (Group I) and 14 – with SPD ³ 600 ng/ml (Group II). Both groups were similar regarding to sex, age, FEV1, smoking status and basic therapy. One or more AE during the year were found in 7 (58.33%) patients of Group I and 12 (85.71%) – of Group II. The data from patient's medical documentation analysis are performed in the table 1.

View this table:



Conclusions 

1. COPD patients with high SPD had higher AE rate and required more frequent both SCS and AB prescription.

2. SPD did not influence on HR in patients with COPD, GOLD stage II-IV.
Platelet transactivation by monocytes promotes thrombosis in heparin-induced thrombocytopenia
Authors: Valerie Tutwiler, Daria Madeeva, Hyun Sook Ahn, Izabella Andrianova, Vincent Hayes, X. Long Zheng, Douglas B. Cines, Steven E. McKenzie, Mortimer Poncz, Lubica Rauova
Journal: Blood (2015)
Crosstalk between epithelium and fibroblasts; implications for COPD
Authors: Emmanuel T. Osei, Corry-Anke Brandsma, Jacobien A. Noordhoek, Wim Timens, Dirkje Postma, Irene Heijink
Journal: European Respiratory Journal (2014)

Background:  We hypothesized that disturbed communication between lung epithelial cells and fibroblasts contributes to tissue remodelling and airway inflammation in COPD. We studied the interaction in a co-culture model with human bronchial cells epithelial cells (16HBE and primary cells from COPD and control) in the upper well and human fibroblasts (MRC-5 and primary cells from COPD and control) in the lower well of a transwell system. We harvested cell-free supernatants to measure pro-inflammatory cytokine IL-8, and cells for mRNA analysis of IL-8 and extracellular matrix (ECM) proteins, including fibronectin, decorin, and collagen. Also, we tested effects of epithelium-conditioned medium on fibroblast inflammatory and ECM responses.   Results:  IL-8 levels were significantly higher upon co-culture than single culture in cell lines as well as primary cells from COPD and control subjects, with fibroblasts being the main source as revealed by mRNA analysis. In contrast, fibroblast mRNA expression of ECM proteins significantly decreased upon co-culture. 16HBE-conditioned medium also strongly increased IL-8 secretion and decreased ECM expression in fibroblasts. This could be blocked by the use of neutralizing IL-1α antibody, suggesting that IL-1α drives the observed changes in fibroblasts. In line with this role for epithelium-derived IL-1α, we observed that both 16HBE and primary epithelial cells secrete substantial levels of IL-1α, in contrast to fibroblasts.   Conclusion:  Together, our data suggests that epithelial cells regulate fibroblast responses by secreting soluble factors (e.g. IL-1α), inducing a switch towards a more inflammatory and less regenerative phenotype, which may have implications for COPD.
An integrated care pathway programme for COPD patients in Singapore
Authors: Gerald Chua, Thong Gan Chee, Yee Mun Choo, Christine Wu, Ryan See, Lynette Kwek
Journal: European Respiratory Journal (2014)

Background/Aim :

Chronic diseases such as COPD (Chronic Obstructive Pulmonary Disease) are longstanding medical conditions that are often debilitating. To assist with the problem in Singapore, JurongHealth has put in place a COPD ICP (Integrated Care Pathway) programme. It emphasises on case management and clinical integration, where a holistic approach is taken by a multidisciplinary team, towards patient care in the acute and community settings.

Methods :

The programme models case management principles after a U.S-based health service organisation, Geisinger. It encourages case managers to actively follow up, educate and equip their patients to manage their medical conditions. They will also monitor the patient's quality of life using the COPD Assessment Tool (CAT), which captures the patient's baseline and best score within the first year of enrolment. Monthly interdisciplinary meetings are held to discuss social and clinical issues of COPD frequent flyers and patients who readmit within 30-days in the preceeding month.

Results :

From July 2012 to September 2013, 166 patients were recruited and care delivery was assessed by an all-or-none care bundle. 70% of care elements in the care bundle were complied by all patients within the first year of enrolment. The overall COPD 30-day readmission rate improved from 36.0% (April to December 2012) to 20.0% (Jan 2013 to Sep 2013). 75.5% of Group B and D patients with baseline CAT score >10 showed >10% improvement in CAT score from their baseline.

Conclusion :

High touch case management and multidisciplinary care within the COPD ICP programme has effectively reduced the 30-day readmission rate, improved the patient's quality of life and their care bundle compliance rate.
Improving use
Authors: Lucy V Harding, Cuong Dang, Robert Young
Journal: BMJ (2007)

Fitzmaurice and Murray remind us that venous thromboembolism is not just a problem among surgical patients but an important cause of morbidity and mortality in medical patients too.1

We work in a hospital that implemented a thromboprophylaxis protocol for medical patients in 2004. In line with the recent recommendations of the UK government's Health Select Committee, the protocol states that every medical patient admitted to the hospital should have a risk assessment for venous thromboembolism and be prescribed thromboprophylaxis with low molecular weight heparin if indicated. When the protocol was introduced it was widely publicised within the hospital and made easily accessible to doctors in the patient's bedside file and on the hospital intranet.

In the year after the protocol had been introduced we audited all cases of hospital acquired venous thromboembolism, to assess concordance with the protocol. We found that only 18% of medical patients who had an indication for thromboprophylaxis according to the protocol were prescribed an appropriate dose of low molecular weight heparin. Furthermore, out of six patients who died due to pulmonary embolism, only two had received low molecular weight heparin, although it was indicated in all six.

Maybe a new approach to the problem is required. Electronic alerts to the need for thromboprophylaxis have been shown to be effective in increasing doctors' use of thromboprophylaxis and reducing rates of venous thromboembolism.2 This system, however, requires complete electronic records of patients' risk factors for venous thromboembolism. An alternative approach might be to mandate thromboembolism risk stratification and linked action as part of the standard admission procedure.
Retinoic Acid-Induced Growth Inhibition and Morphologic Differentiation of Human Neuroblastoma Cells In Vitro&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: N Sidell
Journal: JNCI Journal of the National Cancer Institute (1982)

Retinoic acid (RA) induced concentration-dependent morphologic differentiation and growth inhibition in the LA-N-1 human neuroblastoma cell line. Time course studies demonstrated a significant increase in the formation of long neurites in LA-N-1 cultures within 48 hours of RA addition; maximum expression of differentiation occurred at approximately 4 days. This differentiation profile corresponded to a detectable decrease in [3H]thymidine incorporation at 48 hours and complete inhibition of cell growth after 3-4 days. The RA-induced morphologic differentiation and growth inhibition persisted despite removal of the drug. A soft agar assay system showed that RA also inhibited the ability of LA-N-1 cells to form anchorage-independent colonies and induced morphologic differentiation in colonies that did develop. These findings suggest that RA promoted the differentiation of LA-N-1 neuroblastoma cells, resulting in an altered expression of the malignant phenotype.
Mechanism of Dimethylnitrosamine Metabolism and Activation in Rats2
Authors: H. M. Godoy, M. I. Diaz Gomez, J. A. Castro
Journal: JNCI Journal of the National Cancer Institute (1978)

Journal Article Mechanism of Dimethylnitrosamine Metabolism and Activation in Rats Get access H. M. Godoy, H. M. Godoy 3Laboratorio de Quimica Biotoxicologica, CITEFA, Zufriategui y Varela, Villa Martelli, Pcia. de Buenos Aires, Argentina. Search for other works by this author on: Oxford Academic PubMed Google Scholar M. I. Diaz Gomez, M. I. Diaz Gomez 3Laboratorio de Quimica Biotoxicologica, CITEFA, Zufriategui y Varela, Villa Martelli, Pcia. de Buenos Aires, Argentina. Search for other works by this author on: Oxford Academic PubMed Google Scholar J. A. Castro J. A. Castro 4 3Laboratorio de Quimica Biotoxicologica, CITEFA, Zufriategui y Varela, Villa Martelli, Pcia. de Buenos Aires, Argentina. 4Address reprint requests to Dr. Castro. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 61, Issue 5, November 1978, Pages 1285–1289, https://doi.org/10.1093/jnci/61.5.1285 Published: 01 November 1978 Article history Received: 14 February 1978 Accepted: 09 June 1978 Published: 01 November 1978
Regional hyperinflation in COPD patients: Correlation between lobar hyperinflation and internal flow distribution
Authors: Wilfried De Backer, Samir Vinchurkar, Wim Vos, Cedric Van Holsbeke, Jan De Backer
Journal: European Respiratory Journal (2012)

Background: Diagnosis of COPD patients is mainly based on lung function tests. Severe COPD patients often develop dynamic and static hyperinflation. However, few studies have addressed the association of hyperinflation and internal flow redistribution. This study describes the relation between regional hyperinflation and flow distribution in COPD patients.

Methods: Lobar volume levels in COPD patients (n=39,  =42.1±2.1 %pred) were determined using functional imaging based on CT data (De Backer J. et al, Radiology 2010; 257(3):854-862). Lobar flow distribution was obtained by calculating the relative difference in the TLC and FRC volumes on the lobar level. The flow distribution towards the different lobes was compared to the imaged based volumes of the corresponding lobes.

Results: Statistically significant correlations (R= 0.4, p< 0.04) were observed between lobar flow distribution and lobar volume-hyperinflation with more flow going to more hyperinflated areas.

![Figure][1] 



Conclusion: Internal flow is redistributed towards the hyperinflated zones which means that also inhaled medication would mainly go to the hyperinflation areas leaving other areas partially untreated and this may further enhance the observed flow redistribution.

 [1]: pending:yes
Proliferation of alveolar type II pneumocytes is stimulated by Jagged-1 in vitro
Authors: Rainer Zembacher, Susanna Desole, Caroline Linhart, Kathrin Watzinger, Christian M. Kähler
Journal: European Respiratory Journal (2012)

Notch is an ancient cell-signaling system that regulates the specification of cell fate. Recently, Notch was found to confer antigen presenting cell function on mast cells, induce histamine release in human basophils and regulate migration and survival of eosinophils.  In acute lung injury, alveolar type II cells activate macrophages, secrete soluble mediators, migrate and spread in response to the injury. Additionally, Notch stimulated myofibroblast differentiation and migration of cultured RLE-6TN cells. However, until now, nothing is known on the role of Notch activation regarding proliferation of rat alveolar type II cells.  Rat alveolar type II cells (RLE 6TN) were obtained from the American Type Culture Collection (ATCC no. CRL-2300; Manassas, VA, USA) and were cultured in DMEM/Ham9s F12 containing 10% fetal calf serum and L-glutamine. Cell proliferation was measured by direct cell count and the fluorometric proliferation assay EZ4U basing on tetrazolium salt reduction. Cells were incubated with the test substances in medium containing 0.5% fetal calf serum for 24h at 37°C and 5% CO 2 .  Jagged-1 significantly stimulated proliferation of alveolar epithelial cells within a wide concentration range [5µg/ml to 100pg/ml]. The maximum effect was observed at 100ng/ml. To show specificity of the observed effect, rat alveolar type II cells were preincubated (45 min) and co-incubated with the specific gamma secretase inhibitor DAPT [10 -4  M] which completely abolished the effect of Jagged-1 [ng/ml].  Herewith, we report for the first time that the Jagged-1/Notch signalling pathway is affecting rat alveolar type II cell proliferation in vitro.
Phase I trial of ZD1694, a new folate-based thymidylate synthase inhibitor, in patients with solid tumors.
Authors: S J Clarke, J Hanwell, M de Boer, A Planting, J Verweij, M Walker, R Smith, A L Jackman, L R Hughes, K R Harrap, G T Kennealey, I R Judson
Journal: Journal of Clinical Oncology (1996)

PURPOSE To perform a phase I clinical and pharmacologic study of ZD1694 (Tomudex, Alderley Park, United Kingdom), a new folate-based thymidylate synthase (TS) inhibitor, in patients with advanced malignancy. PATIENTS AND METHODS From February 1991 to January 1993, 61 patients with a range of solid tumor received 161 courses of ZD1694 given as a single 15-minute intravenous infusion every 3 weeks, at escalating doses from 0.1 to 3.5 mg/m2. Pharmacokinetic (PK) analysis was performed with the first two courses of treatment. There were 33 men and 28 women with a median age of 53 years (range, 21 to 73). Fifty-five patients (90%) had previously received chemotherapy. RESULTS Reversible liver toxicity and dose-related gastrointestinal (GI) and bone marrow toxicity occurred at &gt; or = 1.6 mg/m2. Liver function usually returned to normal with repeated treatment, but GI and bone marrow toxicities generally became more severe. No renal toxicity was observed. The maximum-tolerated dose (MTD) was 3.5 mg/m2, at which, in addition to antiproliferative toxicities, four of six patients (67%) developed severe malaise that consisted of anorexia, nausea, and asthenia, with rapidly decreasing performance status that limited re-treatment. Abnormal liver function was also seen in four patients (67%). At 3.0 mg/m2, grades III and IV diarrhea were seen in six of 23 patients (26%) and grade IV myelosuppression in two others. Liver toxicity was self-limiting and not associated with severe malaise. Two patients had a partial response to treatment. PK analysis showed that plasma elimination was triexponential, with pronounced variability in the mean terminal half-life (t1/2gamma) for a given dose ranging from 8.2 to 105 hours. There was a linear relationship between dose and both the area under the concentration-time curve (AUC) and maximum concentration (Cmax), but no clear association between these parameters and response or toxicity. CONCLUSION The dose of ZD1694 recommended for phase II trials is 3.0 mg/m2.
Two clones of methicillin-resistant Staphylococcus aureus in Poland
Authors: Krzysztof Trzciński, Willem van Leeuwen, Alex van Belkum, Pawel Grzesiowski, Jan Kluytmans, Marly Sijmons, Henri Verbrugh, Wolfgang Witte, Waleria Hryniewicz
Journal: Clinical Microbiology and Infection (1997)
Are there gender-specific differences in the short time results of a 3-week inpatient pulmonary rehabilitation (PR) in COPD Patients?
Authors: Nicola Lehbert, Daniel Jelusic, Michael Wittmann, Michael Schuler, Konrad Schultz
Journal: European Respiratory Journal (2014)

Background:  The prevalence and mortality of COPD in women is increasing. Effectiveness of PR is proved on the highest level of evidence. However there is little data concerning gender differences in the results of PR. The objective was to evaluate if PR outcome parameters in men and women differ.   Methods:  In 346 consecutive COPD-patients data of the following parameters was collected at the beginning (T0) and the end (T1) of the PR-programme and compared regarding gender: physical working capacity (6MWD = 6 minute walk distance), dyspnea (MMRC = mod. MRC-dyspnea-scale, TDI=Transition Dyspnea Index) and quality of life (CAT=COPD Assessment Test, SGRQ-sum score = St. George9s Respiratory Questionnaire). Gender-, overtime- and interaction effects were evaluated by variance analyses with repeated measurements.   Results : 219 (63%) patients were male (O age 57.5, O FEV 1  49.8 % pred.), 127 (36.7%) female (O age 57.4, O FEV 1  51.5 % pred.). Baseline and changes over time for both groups are shown in table1. Neither group comparisons nor interactions show significant effects in any outcome (all p>0.1).   Conclusion:  Men and women benefit equally from a pulmonary rehabilitation.
Schizophrenia in ethnic minority groups
Authors: D. Jacobs
Journal: BMJ (2002)

Compiling list of non-diseases is medical arroganceEditor-The arrogance of the concept of compiling a list of non-diseases is breathtaking. 1ad this list been compiled 50 years ago, which illnesses would have been listed?Multiple sclerosis, Crohn's disease, hypothyroidism?The medical community's inability to learn from past mistakes-namely, to acknowledge that most patients are honestly relating their symptoms and sincerely wish to recover-will doom generations of innocent people to the kind of humiliation and insult this ballot encapsulates.Unable to perceive their own ignorance, these commentators will enjoy a brief moment in the spotlight sneering at the proponents of non-diseases, utterly failing to advance medical science.And you wonder why the benighted sufferers of their non-diseases resort to alternative practitioners.