tbuckley/cabot-search huggingface dataset:
P133 Longitudinal Decline In Fev1 In Occupational Asthma Due To Irritants Is Not Altered By Removal From Exposure
Authors: E. Butterfield, G. Walters, V. Moore, P. Nightingale, A. Turner, P. Burge
Journal: Thorax (2014)

<h3>Introduction</h3> Airborne irritants and allergens in the workplace can induce and trigger occupational asthma (OA). OA due to sensitisation is associated with an accelerated rate of decline in FEV<sub>1</sub> (100 mls/yr) compared with healthy controls (25 mls/yr)<sup>1</sup>, which improves on removal from exposure. We sought to describe the rate of FEV<sub>1</sub> decline in patients with irritant-induced OA before and after their removal from exposure. <h3>Methods</h3> Cases of irritant-induced OA reported between 1991 and 2011 were identified from the SHIELD database (a voluntary reporting scheme for OA) and their demographic characteristics and serial FEV<sub>1</sub> measurements were gathered. Generalised estimating equations with an exchangeable correlation structure were used to calculate an average rate of FEV<sub>1</sub> decline for all patients before and after removal from exposure. <h3>Results</h3> A total of 526 FEV<sub>1</sub> readings (179 prior to removal, 347 post removal) were gathered from 52 patients. 30 patients had FEV<sub>1</sub> data both before and after removal; 5 patients had FEV<sub>1</sub> data only before removal, and 17 patients had FEV<sub>1</sub> data only after removal; demographics were not significantly different between the groups. FEV<sub>1</sub> decline prior to removal of the irritant was 44 ml/year (95% CI: 32–58) and FEV<sub>1</sub> decline after removal was 49 ml/year (95% CI: 36–62). There was no significant difference between the intercepts of the two lines, implying no improvement in FEV<sub>1</sub> after removal from exposure. <h3>Conclusion</h3> In this cohort, irritant-induced OA was associated with an accelerated decline in FEV<sub>1</sub>, which persisted after removal from the irritant. These results might be attributed to differences in the underlying pathology of sensitisation and irritant-induced OA, differences in patient behaviour, or differences in treatments offered to the two groups. <h3>Reference</h3> Anees W <i>et al</i>. FEV<sub>1</sub> decline in occupational asthma. <i>Thorax</i> 2006;61:751–5
TWO PRACTICAL POINTS IN CARE OF THE TUBERCULAR.
Authors: WILLIAM PORTER
Journal: JAMA (1900)

As we are getting to know more of the nature and progress of tuberculosis, we are becoming more practical and hopeful in the care of it. Our therapeutics is founded on a definite pathology and is, for that reason, more positive and exact than ever before, and it is not assuming too much to say that the results are better. There is no disease where attention to the minutest detail of hygiene and function is better repaid. Indeed, these considerations are as important as any attempted specific medication, valuable as that may be. The old days of practice, when cod-liver oil was prescribed for the stay-at-home cases and a climatic hypothesis for those who had the money and the courage to go, are superseded by a time when the physician interrogates every organ, endeavors to restore each failing function and individualizes each case, both from the standpoint of general and
Are we predictive engines? Perils, prospects, and the puzzle of the porous perceiver
Authors: Andy Clark
Journal: Behavioral and Brain Sciences (2013)

Abstract The target article sketched and explored a mechanism (action-oriented predictive processing) most plausibly associated with core forms of cortical processing. In assessing the attractions and pitfalls of the proposal we should keep that element distinct from larger, though interlocking, issues concerning the nature of adaptive organization in general.
O10.10 * RESULTS OF NIMOTUZUMAB AND VINORELBINE, RADIATION AND RE-IRRADIATION FOR DIFFUSE PONTINE GLIOMA IN CHILDHOOD
Authors: M. Massimino, V. Biassoni, R. Miceli, E. Schiavello, M. Warmuth-Metz, P. Modena, F. Giangaspero, F. Spreafico, F. Bach, L. Gandola
Journal: Neuro-Oncology (2014)

BACKGROUND: Radiotherapy is the only treatment definitely indicated for diffuse pontine gliomas (DIPG). Data on the role of EGFR signaling in the onset of childhood DIPG prompted the use of an anti-EGFR monoclonal antibody, nimotuzumab. Based on a possible synergistic activity with vinorelbine and radiotherapy, a pilot phase 2 protocol was launched in 2009 that combined nimotuzumab, concomitantly with radiation and vinorelbine. Reirradiation was planned at relapse. Primary end-point for first line treatment was objective response rate (CR + PR + SD) according to RECIST. This paper reports the results of the whole strategy. METHODS: Vinorelbine 20 mg/m2 was administered weekly, together with nimotuzumab 150 mg/m2 in the first 12 weeks of treatment, radiotherapy was delivered from weeks 3-9 for a total dose of 54 Gy. Vinorelbine 25 mg/m2 and nimotuzumab were given every other week thereafter until the tumor progressed or for up to two years. Reirradiation consisted of 19.8 Gy, fractionated into 11 days. Basal and latest MRIs were assessed blindly by an external neuroradiologist. RESULTS: From August 2009, with a median follow-up of 23 months, 25 children, mean age 7.4 years, were enrolled. Response was observed in 24/25 (96%) patients. The nimotuzumab/vinorelbine combination was very well tolerated, with no acute side-effects. Nine of 13 locally relapsing patients were re-irradiated. The 1-year PFS and OS were 30 ± 10% and 75 ± 9%, respectively; the 2-year OS was 28 ± 11% and the median OS was 14.6 months. CONCLUSIONS: This strategy has interesting results and deserve further investigation.
INTRAVASCULAR IMAGING-GUIDED PERCUTANEOUS TRANSLUMINAL PULMONARY ANGIOPLASTY FOR PERIPHERAL PULMONARY STENOSIS AND PULMONARY TAKAYASU's ARTERITIS
Authors: Ryoji Yanagisawa, Masaharu Kataoka, Takumi Inami, Nobuhiko Shimura, Haruhisa Ishiguro, Takashi Kawakami, Keiichi Fukuda, Hideaki Yoshino, Toru Satoh
Journal: Journal of the American College of Cardiology (2016)
THE IMPACT OF CELLULAR ADHESION MOLECULES ON MORTALITY IN PATIENTS WITH STABLE ATHEROSCLEROSIS
Authors: Georg Goliasch, Oswald Wagner, Markus Exner, Renate Koppensteiner, Gerald Maurer, Martin Schillinger, Erich Minar, Wolfgang Mlekusch, Matthias Hoke
Journal: Journal of the American College of Cardiology (2015)
P4-11-02: Insulin-Like Growth Factor-1 (IGF-1), Insulin-Like Growth Factor Binding Protein-3 (IGFBP-3) and Lobule Type among Women in the Nurses' Health Study II (NHS II).
Authors: LC Collins, MS Rice, D Shen, JL Connolly, SJ Schnitt, RM Tamimi
Journal: Cancer Research (2011)

Abstract In a previous analysis of women enrolled in NHSII, we found that among women diagnosed with benign breast disease (BBD), those with predominant type 1/no type 3 lobules were at lower risk of subsequent breast cancer compared to women with other lobule types. Additionally, studies in animal models suggest that higher levels of IGF-1, a polypeptide hormone involved in the proliferation/differentiation of normal mammary epithelium, may inhibit involution of breast lobules. However, the interaction between IGF-1 levels and lobule types in determining breast cancer risk has not been previously evaluated. Therefore, we examined the association between IGF-1 levels and lobule type among women with BBD. Methods: We conducted a cross-sectional study among 484 women in NHSII with biopsy-confirmed BBD between 1993–2001 who had blood samples available for determining levels of IGF-1 and IGFBP-3. A pathologist, blinded to exposure status, classified lobule type on biopsy slides according to the number of acini per lobule (type 1 &amp;lt; 12; type 2∼50; type 3∼80 acini). Lobule type was classified into (1) predominant type 1/no type 3 lobules or (2) other lobule types. Multivariate logistic models were used to assess the associations between plasma IGF-1, IGFBP-3, and IGF-1/IGFBP-3 levels with lobule type. Models were adjusted for age, IGF-1 batch and additional potential confounders in secondary analyses. Results: In univariate analyses, older age at biopsy, higher body mass index, postmenopausal status, nulliparity, and lower IGF-1 levels were associated with predominant type1/no type 3 lobules (p&amp;lt;0.05). In multivariate logistic models adjusting for age, higher IGF-1 levels were associated with a decreased risk of predominant type 1/no type 3 lobules (OR quartile 4 vs. quartile 1 = 0.35, 95%CI: 0.15−0.81). Greater IGF-1/IGFBP-3 ratio was also associated with a decreased risk of predominant type1/no type 3 lobules (OR quartile 4 vs. quartile 1 = 0.24, 95%CI: 0.10−0.57). These associations persisted, though were slightly attenuated, in models adjusting for additional potential confounders. Conclusion: Higher IGF-1 levels and greater IGF-1/IGFBP-3 ratios are associated with a decreased risk of predominant type 1 lobules/no type 3 lobules among women with BBD in the NHSII. Whether this association contributes to the mechanism by which IGF-1 confers an elevated breast cancer risk requires further investigation. Acknowledgements: This work was supported by T32 CA09001-35 CA124865, R01 CA050385, and the Breast Cancer Research Foundation Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-11-02.
Abstract 4475: Inhibition of aminoacid biosynthetic pathways lead to increase sensitivity to anthracyclines in Saccharomyces cerevisiae
Authors: Hernan Flores-Rozas, Tryphon Mazu
Journal: Cancer Research (2011)

Abstract Anthracycline antibiotics are commonly used antineoplastic agents that provide significant therapeutic efficacy in the treatment of both solid tumors and hematological cancers. Although there is a dose-dependent response in the use of these agents, there is also a dose related toxicity associated to them. The most serious toxicity of the use of anthracyclines is chronic cardiotoxicity. To increase our knowledge of the pathways that protect cells from the cytotoxic effects of anthracyclines, we carried out a genetic screening in the eukaryotic model organism S. cerevisiae, to identify gene defects that generate cells hypersensitive to doxorubicin. Our findings indicate that inactivation of some aminoacid biosynthetic pathways hypersensitize cells to doxorubicin. Defects in the biosynthesis of threonine lead to an increase sensitivity to doxorubicin up to 1000-fold higher than wild type cells, while inactivation of serine and tryptophan pathways lead to an increase of up to 100-fold higher than wild type cells. We present evidence that accumulation of intermediate metabolites in the pathway are responsible for the hypersensitivity to doxorubicin and discuss the potential use of these compounds as chemotherapeutic enhancing agents. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4475. doi:10.1158/1538-7445.AM2011-4475
Use of the modified Borg scale and numerical rating scale to measure chronic breathlessness: a pooled data analysis
Authors: Miriam J. Johnson, Lucy Close, Suzie C. Gillon, Alex Molassiotis, Paul H. Lee, Morag C. Farquhar
Journal: European Respiratory Journal (2016)

The subjective nature of the experience of chronic breathlessness (dyspnoea) creates challenges for patients who need to communicate its intensity, and for clinicians and researchers who need to measure the symptom in order to plan management and assess the effect of interventions. Measuring chronic dyspnoea in clinical studies: numerical rating scale better than the modified Borg scale <http://ow.ly/XZc1G> With thanks to members of the Breathlessness Research Interest Group who provided data: Claudia Bausewein (University of Munich, Munich, Germany); Saskie Dorman (Poole Hospital NHS Foundation Trust, Poole, UK); Morag Farquhar and Sara Booth (University of Cambridge, Cambridge, UK); Alex Molassiotis (The Hong Kong Polytechnic University, Hong Kong); Stephen Oxberry (Calderdale and Huddersfield NHS Foundation Trust, Huddersfield, UK); Farida Malik (Eastbourne and East Sussex Healthcare NHS Trust, Eastbourne, UK); Steffen Simon (University of Cologne, Cologne, Germany); Kyle Pattinson (University of Oxford, Oxford, UK); Janelle Yorke (University of Manchester, Manchester, UK); Patrick White (King's College London, London, UK).
Are selective serotonin reuptake inhibitors (SSRIs) a risk factor for post-polypectomy bleeding?
Authors: P. Katsinelos, S. Gkagkalis, G. Chatzimavroudis, C. Zavos, J. Kountouras
Journal: Endoscopy (2013)

We read with great interest the letter of Sarkis et al. [1] and the reply of Repici et al. [2] on post-procedure bleeding after cold polypectomy and biopsy in the gastrointestinal tract. It is interesting that in the study by Sarkis et al. one patient with post-biopsy bleeding was under treatment with paroxetine (the oldest selective serotonin reuptake inhibitor [SSRI]). Moreover, Repici et al. note that antidepressants may increase the post-procedure bleeding risk. However, there is no study that relates post-polypectomy or biopsy bleeding with use of SSRIs.
Abstract P6-04-08: Microarray Characterization of 24 Cases of Pure Mucinous Carcinoma of the Breast
Authors: AJ Sanchez-Salazar, SR Gunn, I-T. Yeh
Journal: Cancer Research (2010)

Abstract Background: Mucinous carcinoma of the breast has been shown to be a distinct histological entity with a better clinical prognosis than invasive ductal carcinoma, NOS. Only a few cases have thus far been studied by molecular analysis. The purpose of this is study is to further evaluate the genomic changes in mucinous carcinoma of the breast. Design: 24 pure mucinous breast carcinomas with available fresh frozen tissue were retrieved from our files. The cases were reviewed for histologic grade (SBR), mitoses, percent mucin, intracytoplasmic mucin, type A or B mucinous carcinoma, and estrogen receptor (ER) and progesterone receptor (PR) expression. Follow-up was available for 13 patients and included 4 recurrences. Representative sections of the tumors were dissected from the normal tissue present in the blocks and were assayed by Agilent (Santa Clara, CA, USA) human genome CGH microarray kit 105A. Analysis was performed using Agilent (Santa Clara, CA, USA) genomic workbench 5.0 software. Results: The 24 mucinous carcinomas were composed of 19 type A and 5 type B mucinous carcinomas, including 21 with &amp;gt;60% mucin and 3 with &amp;lt;60% mucin. Seven cases contained intracytoplasmic mucin. Tumors were grade 1 in 20 cases and grade 2 in 4 cases. Mitotic count per 10hpfs was 0 or 1-2 in 19 cases and &amp;gt;3 in 5 cases. ER was positive in all cases, and PR was positive in all but 4 cases. Analysis of the genome arrays showed that 17 of the cases had a complex level of genetic instability with three or more (up to 15) of the chromosomes showing instability while four show only one or two chromosomes affected. On the other hand, there are no abnormalities found in four of the cases. The most frequently affected chromosome is chromosome 1 which is involved in 12 of the cases, with three cases showing 1p partial loss/full loss, and nine cases showing 1q partial gain/full gain. Gains were also commonly seen in 8p, 8q, 11q, 16p, 17q and 20q. Losses were most frequently seen in 6q, 11q, 16q and 17p. Four of five Type B tumors exhibited a complex pattern, and all four grade 2 tumors had a complex pattern. Of the tumors that recurred, three of four had a complex pattern of genetic instability. Conclusions: Evaluation of pure mucinous carcinomas studied showed a high level of genomic complexity with multiple chromosomal changes in most cases. Tumors that were grade 2 and mucinous type B tumors tended to be of higher complexity than grade 1 and type A mucinous tumors. The most commonly affected chromosomes include chromosomes 1, 6, 8, 11, 16, and 17. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-04-08.
Abstract 1372: Microvessel proliferation by co-expression of endothelial nestin and Ki-67 is associated with a basal-like phenotype and aggressive features in breast cancer
Authors: Kristi Krüger, Ingunn Marie Stefansson, Karin Collett, Jarle Birger Arnes, Turid Aas, Lars Andreas Akslen
Journal: Cancer Research (2012)

Abstract Angiogenesis, the formation of new blood vessels from pre-existing ones, is essential in tumour growth and metastasis. Microvessel density (MVD) is the most widely used method for quantification of tumour angiogenesis. We here present a novel angiogenesis marker, microvessel proliferation (MVP) based on a dual immunohistochemical stain of nestin and Ki-67. Nestin is an intermediate filament protein expressed in a variety of undifferentiated cells, including newly synthesized endothelial cells (1-3), and used in this study to stain the vasculature. Proliferating cells were recognized by their Ki-67 positivity, and immature microvessels were recognized by their nestin positivity combined with their morphology. Proliferating microvessels contains endothelial cells co-expressing nestin and Ki-67. Microvessel proliferation was estimated by vascular proliferation index (VPI), the ratio of vessels containing immature proliferating endothelial cells, and the total number of immature vessels. VPI was evaluated in 178 breast cancer tissue sections. High VPI showed significant association to several markers of aggressive breast cancer, including negative estrogen receptor (ER) status (p=0.003), high tumour cell proliferation by Ki-67 (p=0.004), high p53 expression (p=0.001), five immunohistochemical profiles for the basal-like phenotype (odds ratios (OR); range 2.8-6.3), and the triple negative phenotype (TNP)(p=0.040). Concerning the mode of detection, high VPI was three times more likely to be presented in an interval detected breast cancer compared with a screening detected (OR: 3.0, p&amp;lt;0.0005). Both in univariate and multivariate analysis, high VPI was significantly associated with poor survival (p=0.034 and p=0.022, respectively). In conclusion, activated angiogenesis, estimated by microvessel proliferation, is associated with several markers of aggressive breast cancer phenotype, basal-like breast cancer, interval detection, and a significant predictor of prognosis in this series of breast cancer. 1. Lendahl U, Zimmerman LB, McKay RD. CNS stem cells express a new class of intermediate filament protein. Cell. 1990 Feb 23;60(4):585-95. 2. Mokry J, Cizkova D, Filip S, Ehrmann J, Osterreicher J, Kolar Z, et al. Nestin expression by newly formed human blood vessels. Stem Cells Dev. 2004 Dec;13(6):658-64. 3. Mokry J, Ehrmann J, Karbanova J, Cizkova D, Soukup T, Suchanek J, et al. Expression of intermediate filament nestin in blood vessels of neural and non-neural tissues. Acta Medica (Hradec Kralove). 2008;51(3):173-9. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1372. doi:1538-7445.AM2012-1372
A10.08 Detailed analysis of the effect of cryopreservation on the viability and cytokine release of human synovial tissue
Authors: M de Vries, MGA Broeren, MB Bennink, PLEM van Lent, PM van der Kraan, MI Koenders, RM Thurlings, FAJ van de Loo
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> Human synovial tissue derived from joint surgery of osteoarthritis (OA) and rheumatoid arthritis (RA) patients is valuable material for studying fundamental research questions. It would be ideal to store and collect all this valuable tissue for later use. In this study cryopreservation solutions are validated for their capability to preserve the tissue as freshly obtained material. <h3>Materials and methods</h3> Human synovial OA tissue was derived (n = 4), with informed consent, from joint surgery and frozen as 3 mm biopsies. Cryosections were made to prove synovial origin. Biopsies were cryopreserved by slow freezing using several cryoprotectant (CPA) solutions (Cryostor CS2, Cryostor CS10, CryoSFM, Biofreeze and standard freezing medium containing 10% DMSO and 10% FCS). For slow freezing an isopropanol container was used assuring a temperature decrease of 1°C/min. Frozen tissues were stored for 7 days in liquid nitrogen. Thawing was performed at 37°C, followed by quick removal of the CPA solution. <h3>Results</h3> To asses general viability after thawing the tissue was cultured overnight. Both the ATP and XTT assays showed viability rates up to 90% of non frozen tissue. However, decreased viability (60%) was observed with higher concentrations of DMSO (CS10 and standard media, XTT) and the complete absence of DMSO (Biofreeze, ATP). Next, the RNA integrity number (RIN) was determined 24 h after thawing to ensure the RNA is suitable for gene array experiments. A high RIN (˜8) was found in all conditions. Stress genes (<i>CASP3, HSPA1A, HSP27, MCL1, BAX, CD95, p53</i>) described to be up/downregulated after cryopreservation did not show deviations from the non frozen tissue in the four donors tested. However, studying OA characteristic gene expression (<i>TIMP3, CCL18, MMP9</i>) showed that the Biofreeze medium had most changes (up/down) compared to non frozen tissue. Furthermore, we showed that the tissue was able to respond to inflammatory stimuli (Pam3Cys/LPS) as cytokine secretion (IL1b, TNFa, IL6, IL8) was highly upregulated. <h3>Conclusion</h3> Evaluation by two viability assays, stress – and disease characteristic gene expression, and cytokine secretion showed that during a short-time culture of human synovial tissue the disease characteristic phenotype was unchanged after cryopreservation.
Cell Proliferation and Carcinogenesis: A Brief History and Current View Based on an IARC Workshop Report
Authors: L. Tomatis
Journal: Environmental Health Perspectives (1993)

The International Agency for Research on Cancer recently convened a Working Group of Experts (June 11-18, 1991) to discuss the use of information on carcinogenesis mechanisms in carcinogenic risk identification. The role of cell proliferation in carcinogenesis was among the items discussed in detail. It was recognized that cell proliferation is an important mechanistic aspect for both genotoxic and nongenotoxic carcinogens. It may act at each stage of the carcinogenesis process altering the size of the pool of cells at risk for a next event. Cell proliferation was considered to be important, especially as a) an integral part of the process of converting DNA adducts to mutation, b) an enhancing factor for the mutation frequency by inducing errors in replication, and c) an important factor in determining dose-response relationships for some carcinogens. It was also recognized that not all agents that induce cell proliferation are necessarily involved in carcinogenesis; for example, a) not all skin hyperplasia-inducing compounds are skin tumor promoters, b) agents that induce regenerative cell proliferation appear to have different effects on tumor induction from agents that have a direct mitogenic effect, and c) the carcinogenic activity of many nonmutagenic agents depends on the continuous administration of the agent. In addition, tissues with a high rate of cell proliferation do not have a higher risk of developing cancer. Thus, no simple relationship exists between cell proliferation and carcinogenesis.
Prophylaxis and Treatment of Heat-Reaction States
Authors: Louis Friedfeld
Journal: New England Journal of Medicine (1949)

DURING a severe heat wave in the summer of 1937, 8 of the aged residents of the Home of Old Israel in New York City succumbed in a single day under circumstances that left no doubt that the high environmental temperature was the precipitating cause of death. During the much more severe heat wave in August, 1948, not a single death occurred in the same institution although the mortality rate for the city as a whole was higher than that in 1937. It is believed that the reason for the difference is that the unfortunate experience of 1937 had led . . .