tbuckley/cabot-search huggingface dataset:
Early detection of colorectal cancer from patient blood plasma using microRNA-based q-rt-PCR
Authors: Søren J. Nielsen, Nana Jacobsen, Jacob U. Fog, Hanni Willenbrock, Adam Baker, Thorarinn Blondal, Martin Vincent, Torben Oerntoft, Hans Joergen Nielsen, Ib J. Christensen, Claus L. Andersen, Søren Møller, Jan Stenvang, Nils Brünner
Journal: Clinical Cancer Research (2010)

Abstract microRNAs (miRNAs) constitute a recently discovered class of small RNAs (typically 21-23 nt) that function as post-transcriptional regulators of gene expression. Current estimates indicate that more than one third of the cellular transcriptome is regulated by miRNAs, and that each miRNA potentially regulates hundreds of different mRNAs. As a consequence, miRNAs have been proposed to be master regulators of cellular state. This hypothesis has been borne out by a large number of studies demonstrating a causal link between miRNA dys-regulation and numerous disease states, including a diverse array of human cancers. Furthermore, the high stability of miRNA in common clinical source materials (e.g. FFPE blocks, plasma, serum, urine, saliva, etc.) and the ability of miRNA expression profiles to accurately classify discrete tissue types and disease states have positioned miRNA quantification as a promising new tool for a wide range of diagnostic applications. Colorectal cancer (CRC) ranks 4th in terms of prevalence and second in numbers of deaths among cancers of the western world. Although early detection of CRC leads to a favorable prognosis, and though CRC can easily be detected in the locally restricted state using a variety of diagnostic procedures, frequent late diagnosis means that CRC is still a leading cause of cancer mortality worldwide. Current procedures suffer from one or more disadvantages within areas such as cost, safety, inconvenience to the patient with the consequence of low compliance, lack of trained personnel, sensitivity etc, thereby precluding their adoption as a population screening tool. There is therefore an unmet need for a generally acceptable CRC screening assay. To facilitate discovery and clinical transfer of miRNA-based diagnostic markers, we developed a genome-wide LNA™-based miRNA q-rt-PCR platform with unparalleled sensitivity and robustness. The platform uses a single RT reaction to profile &amp;gt;700 human miRNAs from 2 predefined 384 well plates and thus allows high-throughput profiling of miRNAs from important clinical sources without the need for pre-amplification. Using this system, we have profiled a large number of plasma samples from localized and regional CRC patients, and from matched healthy controls. An extensive QC system has been implemented in order to secure technical excellence and reveal any unwanted bias in the dataset. We will present our approaches to data normalization and the results of signature development using linear classification methods. We show that we can detect the majority of cancer cases with good specificity, using a cross-validation approach. In summary, our results show that minimally invasive early detection of CRC using a clinically viable approach is feasible.
Respiratory syncytial virus (RSV) causes ciliary dyskinesia but not loss of frequency during infection of human ciliated respiratory epithelial cells in culture
Authors: Claire Smith, Gwyneth Williams, Andrew Rutman, Andrew Easton, Peter Andrew, Chris O'Callaghan
Journal: European Respiratory Journal (2012)

Aim To determine the effect of RSV on ciliary function using ciliated air–liquid interface (ALI) cultures.  Introduction: RSV targets ciliated respiratory epithelial cells for infection1. Two previous studies on the effect of RSV on ciliated cultures have shown different effects, one describing rapid ciliostasis2 and another describes no cytopathic effect1.  Methods Ciliated epithelial cells were cultured from nasal and bronchial brush biopsies. Cells were infected with RSV (A2) for up to 72h. Ciliary beat frequency (CBF) and pattern (CBP) were observed with a high-speed video camera. The cells were fixed and stained using anti-RSV (FITC) and anti-acetylated tubulin (Alexa594) antibodies. Confocal optical sectioning and electron microscopy (EM) was also performed.  Results CBP showed a higher proportion of dyskinetic cilia following RSV infection. The median (IQR) dyskinesia index was increased as early as 24h and at 72h had increased to 33% (25-42%) compared with controls 13% (11-14%). CBF was unaffected by RSV infection. By 72h the ultrastructure of the ciliated epithelium was abnormal following RSV infection with an increased in ciliated cells exhibiting loss of cilia and an increase in ciliated cells with mitochondrial damage. Furthermore, RSV antigens were observed on the apical surface of the cell and had extended the full length of the cilial shaft.  Conclusion RSV infection of ciliated cells results in increased dyskinesia of cilia, whilst CBF is maintained. Epithelial damage was preferentially seen in ciliated cells.  Refs  1. J Virol. 2005;79(2):1113-1124  2. Arch Otolaryngol Head Neck Surg, 1998;124(7):777-83.
Intermittent oxaliplatin (oxali) administration and time-to-treatment-failure (TTF) in metastatic colorectal cancer (mCRC): Final results of the phase III CONcePT trial
Authors: A. Grothey, L. L. Hart, K. M. Rowland, R. H. Ansari, S. R. Alberts, N. M. Chowhan, A. Shpilsky, H. S. Hochster
Journal: Journal of Clinical Oncology (2008)

4010 Background: About 60% of mCRC patients (pts) discontinue oxali prior to disease progression (PD), largely driven by cumulative neurotoxicity (NT). CONcePT (Combined Oxaliplatin Neurotoxicity Prevention Trial) was initiated to test if an intermittent oxali (IO) schedule of FOLFOX/bevacizumab (BV) allows pts to remain on therapy longer compared to a conventional oxali (CO) "treat-to- failure" approach. To explore the impact of IV calcium/magnesium (CaMg: Ca-gluconate 1g, Mg-sulfate 1g, pre/post oxali) on NT, pts were randomized in a 2x2 factorial design (IO vs. CO) x (CaMg vs. placebo [PL] - double-blinded). Methods: Eligibility criteria included measurable disease, PS 0–1, no neuropathy. In CO arms, pts received mFOLFOX7 (oxali 85mg/m2, LV 200mg/m2, 5FU 2,400mg/m2 x 46h) plus BV (5mg/kg) q2wks. In the IO arms, pts alternated every 8 cycles with and without oxali. After 140 pts, a protocol amendment eliminated the CaMg vs. PL randomization and 40 subsequent pts all received CaMg. TTF (primary endpoint) was calculated as time from randomization to treatment discontinuation for any reason, including PD, death, toxicity, investigator or patient preference. Results: The study was terminated 6/07 by the IDMC based on unadjudicated tumor response data suggesting lower RR for CaMg compared with PL. In the 2x2 phase of the trial (n=139 treated pts), median age was 64y (30–88), 53% PS 0, 55% male, 80% colon, 22% prior adjuvant chemo, 12% prior radiation. Aes were the main cause of treatment failure (35% of pts, IO 28% vs. CO 43%); 22% of failures were due to PD (IO 23% vs CO 21%). Only 1 pt in the IO arm required early reintroduction of oxali. A 2-factor Cox regression model of TTF revealed a statistically significant effect for IO vs CO (median TTF 25 vs 18 wks, p=0.0025, HR=0.58, 95% CI 0.41- 0.83), but not for CaMg vs PL (p=0.1179, HR=1.32, 95% CI 0.93–1.86). Conclusions: Despite early termination, CONcePT met its primary endpoint, demonstrating that IO results in increased time on therapy compared to CO. This strategy is particularly useful in extending time on first-line therapy for oxali/BV combinations. Final results on RR, PFS, and safety (including NT) will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration sanofi-aventis Genentech, Roche, sanofi-aventis Genentech, sanofi-aventis
Comparison of distal lung innervation in human and guinea pig precision-cut lung slices (PCLS)
Authors: Marco Schlepütz, Annette D. Rieg, Marc Bernau, Jan W. Spillner, Alberto Perez-Bouza, Rüdiger Autschbach, Stefan Uhlig, Christian Martin
Journal: European Respiratory Journal (2011)

Introduction:  PCLS from human tissue are well suited to study peripheral airway responses. Since autonomic nerves are involved in airway control and in several diseases including allergic airway hyperreactivity, we characterized distal lung innervation in guinea pigs (GP) with respect to bronchoconstriction (BC) and compared the results to those with human PCLS.   Methods:  PCLS were prepared from GP or human lung tissue. Neural activation was triggered by electric field stimulation (EFS) or capsaicin addition. Cholinergic innervation was verified by atropine. Capsaicin was used to show excitatory non-adrenergic non-cholinergic (eNANC) nerves. Application of Ruthenium red or SKF96365 confirmed transient receptor potential (TRP) channel contributions upon eNANC activation.   Results:  GP and human PCLS were both sensitive to EFS and airways contracted to 39±26% of the initial airway area (%-IAA) and 42±30%-IAA, respectively. Frequency response curves were also similar. For both species, EFS-induced BC was decreased after the addition of atropine. Capsaicin contracted GP and human airways to 18±15%-IAA and to 62±6%-IAA, respectively. Capsaicin-triggered BC was inhibited in GP by Ruthenium red and SKF96365. Both inhibitors also reduced EFS-induced BC in PCLS from GP.   Conclusion:  Both species contain atropine sensitive cholinergic and capsaicin sensitive eNANC nerves. In addition, GP PCLS were sensitive to TRP channel inhibitors allowing the study of their contribution in the pathogenesis of lung diseases. In conclusion, GP PCLS represent a useful model to study pharmacological aspects of lung innervation and resemble the human distal lung innervation.
Adipokines and ghrelin in chronic obstructive pulmonary disease
Authors: Evgenia Kochetkova, Ludmila Ugay, Ylia Maistrovskaya, Tatiana Sourovenko, Gilbert Massard
Journal: European Respiratory Journal (2013)

Objective: to determine associations between the adipokines tumor necrosis factor-alpha (TNF-a) and its receptors sTNFR I, II, leptin, adiponectin, resistin, ghrelin, pulmonary function testing, bone mineral density (BMD) and nutritive status in severe and very severe chronic obstructive pulmonary disease COPD.  Materials: we determined BMD, serum adipokine and ghrelin in 48 patients with severe and very severe COPD and 52 age and sex matched controls. BMD at lumbar spine (LS) and femoral neck (FN) and parameters of body composition were measured by dual-energy X-ray absorptiometry.  Results: the levels of adiponectin, resistin, TNF-a and its receptors sTNFR I, II were higher, but leptin and ghrelin levels were low in COPD than in controls. It was a correlation between leptin (r=0,58, p  Conclusion: Results shows possibly role of adipokines and ghrelin in the increasing of bone loss in severe and end stage COPD. However, larger studies are needed to further evaluate the relationship between adipokines and BMD in COPD.
Non invasive assessment of pulmonary shunt in adults with liver disease
Authors: Georgia Spentzou, Sunil Sanka, Matt Rutter, Nick Fung, Robert Ross Russell
Journal: European Respiratory Journal (2011)

Introduction:  The oxygen dissociation curve charts the relationship between haemoglobin saturation (SaO2) and arterial pO 2 . Less well known is the relationship between the inspired oxygen (FiO2) and SaO2, which reflects aspects of the oxygen cascade that affect the transfer of oxygen into the blood.  A number of models describe this cascade and this allows reconstruction of the curve from a number of data points, allowing estimation of the shunt and whole lung VQ ratio. Its value lies in the simplicity with which both FiO 2  and SaO 2  can be measured.  We are undertaking a “proof of concept” study evaluating shunt in adults undergoing assessment for liver transplantation, where pulmonary shunt is an important clinical problem.   Methods:  Adults breathe an O 2 /N 2  mix with an FiO2 between 0.14 and 0.35. After equilibration, SaO 2  is recorded. At least 3 data points are collected, and analysed using previously validated methodology [1] recently adapted for MATLAB.   Results:  To date (February 2011) we have studied 9 patients with this technique. All tolerated the procedure well. Studies were performed in our respiratory laboratory and took between 20 and 30 minutes to complete.  Shunt varied between 2% and 20% and VQ ratios between 0.78 and 1.5. Patients are also having shunt assessed by VQ scans, and these data will be compared.   Conclusions:  This technique offers a very simple and well tolerated test that quantifies both shunt and VQ mismatch. It only requires an oximeter and a supply of nitrogen. Given that current methods for assessing these parameters require specialised equipment and are time consuming, it may provide an effective test for shunt or VQ matching in a wide range of patients.   Reference:   1Eur J Anaesthesiol 1995:12;375-386.
Annals Graphic Medicine - Sign Out
Authors: Ryan Montoya
Journal: Annals of Internal Medicine (2015)

Web Exclusives6 October 2015Annals Graphic Medicine - Sign OutFREERyan Montoya, MDRyan Montoya, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G15-0003 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Disclosures: The author has disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G15-0003.Author/Illustrator Information: Ryan Montoya, MD, is a U.S.-trained family medicine physician and comic book artist. He works and is currently based in Bosnia and Herzegovina, and next year will be moving to Mumbai, India. His comics, illustrations, and essays can be found at www.rjmontoya.tumblr.com. E-mail: [email protected]com.Author Contributions: Conception and design: R.J. Montoya.Drafting of the article: R.J. Montoya.Critical revision for important intellectual content: R.J. Montoya.Final approval of the article: R.J. Montoya. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 6 October 2015Volume 163, Issue 7Page: W141-W145KeywordsConflicts of interestDisclosureHealth care ePublished: 6 October 2015 Issue Published: 6 October 2015 Copyright & PermissionsCopyright © 2015 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Impact of pulmonary rehabilitation on quality of life in patients with silica exposure associated with progressive massive fibrosis
Authors: Margarida Redondo, Filipa Pires, Paula Martins, Luis Gaspar, Emilia Araujo, Agostinho Marques, Isabel Gomes
Journal: European Respiratory Journal (2014)

Background : Silica exposure associated with progressive massive fibrosis is a severe pneumoconiosis currently uncommon in developed countries and mainly occurring in clusters. Data regarding the impact of a pulmonary rehabilitation (PR) program in these patients is scarce.  Objective : To evaluate QoL impact of a PR program in these patients using a generic health questionnaire (SF-36).  Methods : Retrospective 5-years study of the patients who attended an outpatient PR program and completed the Portuguese version of the SF-36 questionnaire before and after the PR program.  Results : Twelve patients were referred to PR program, although only 6 patients completed the questionnaire before and after the PR program. The patients were male (100%), with a median age of 44.5 years and significant lung function impairment (FEV1 median value of 43.2%). PR program included exercise training, with a median duration of 10.5 weeks. From the beginning to the end of PR program, the median scores for the physical component of the SF-36 questionnaire were: physical function 27.5% to 50% (+22.5%); physical role: 0% to 0% (=); bodily pain: 47.5% to 52% (+4.5%); general health: 24.1% to 22.5% (-1.6%). For the mental component the median scores were: vitality 20% to 40% (+20%); social function 43.7% to 68.7% (+25%); emotional role 0% to 0% (=); mental health 48% to 66% (+16%).  Conclusions : Although a positive impact was found in the physical component, more items of the mental component were clearly improved. These data suggests that the scope of positive effects of a PR program in these severely ill patients is beyond the perception of physical related abilities.
Severity of COPD is linked to decreased histone deacetylase activity
Authors: S A Nachman
Journal: Thorax (2005)

▴ Ito K, Ito M, Elliott WM, et al . Decreased histone deacetylase activity in chronic obstructive pulmonary disease. N Engl J Med2005;352:1967–76

[OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4]



Histone acetylation status depends on the equilibrium between the activities of histone acetyltransferase (HAT) and histone deacetylase (HDAC). Acetylation prompts unwinding of histone and allows DNA transcription and production of cytokines. In alveolar macrophages HDAC is a key molecule in repressing the production of pro-inflammatory cytokines.

In this study the authors attempted to correlate changes in HDAC activity and …

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Prostate Biopsy Strategies: Current State of the Art
Authors: Badar M. Mian
Journal: Journal of the National Comprehensive Cancer Network (2004)

Prostate-specific antigen testing and prostate biopsy have revolutionized our ability to detect prostate cancer at an early stage. The transrectal ultrasound-guided biopsy procedure has undergone a number of modifications over the past 10 years to meet our goal of early detection of cancer at a curable stage. Biopsy schemes have evolved from lesion-directed biopsies to systematic mapping of the peripheral zone of the prostate, which harbors almost all of the significant tumor foci. An increase in the number of biopsy cores from 6 to 10 (or 12) has resulted in a significant improvement in the detection of clinically localized cancer, without any appreciable increase in the number of indolent cancers. Current biopsy schemes also have enhanced our ability to determine the true prognostic value of pathologic lesions such as high-grade prostatic intraepithelial neoplasia and atypical small acinar proliferation which have been associated with cancer detection in repeat biopsies. I discuss the rationale behind, and the outcomes of, various biopsy strategies. More than 15 years after PSA testing was popularized for early detection, a number of men are presenting for evaluation regarding repeat prostate biopsy for various clinical indications. The indications, biopsy scheme, and cancer detection rates for repeat prostate biopsy are discussed in detail.
Impaired endothelial vasoreactivity and markers of systemic inflammation in overlap syndrome
Authors: Parul Khare, Anjana Talwar, Ashok Jaryal, Randeep Guleria, Chandran Dinu, Kishore Kumar Deepak
Journal: European Respiratory Journal (2013)

Introduction Impairment of systemic endothelial reactivity (SER) has been observed in Chronic Obstructive Pulmonary Disease (COPD) and Obstructive Sleep Apnea (OSA). The present study investigates the relation between SER and systemic inflammation in patients of Overlap Syndrome (OS) of COPD and OSA.

Methods The study was conducted on 31 COPD patients and 14 healthy controls. On the basis of polysomnography, the patients were divided into COPD only group \[Apnea-Hypopnea Index (AHI)  5) (n= 15). SER was assessed by measuring changes in pulse wave amplitude (PWA), Maximum slope of upstroke (MSU) and Pulse Transit Time (PTT) derived from the photoplethysmographic waveform during reactive hyperemia (RH). Additionally, C-reactive protein(CRP) in serum was estimated by ELISA.

Results Maximum percentage change in PWA during RH was significantly lower in COPD only group [23.61% (12.02-34.07) p 0.05).Similar responses were seen in MSU in all the groups. CRP levels were higher in COPD (p<0.001) and OS group (p<0.0001). Maximum percentage change in PWA negatively correlated with CRP levels in COPD(r= -0.5695) and OS group (r= -0.5214) and positively correlated with FEV1% predicted in COPD and OS group. AHI did not correlate with vascular function parameters in Overlap group.

Conclusion The patients with Overlap Syndrome have impaired SER which correlates with CRP levels. However, no additive effect of OSA was observed on impaired SER in patients with Overlap Syndrome.
Klebsiella pneumoniae bacteraemia in a region of Canada
Authors: J. Pépin, N. Yared, I. Alarie, L. Lanthier, A. Vanasse, P. Tessier, J. Deveau, M.-N. Chagnon, R. Comeau, P. Cotton, S.J. Libby, L. Valiquette
Journal: Clinical Microbiology and Infection (2009)
Tumor Immunity to Murine Plasma Cell Tumors. V. Genetic Control of the In Vitro Cytotoxic T-Cell Response to Plasma Cell Tumor-Associated Antigens of NZB Mice<xref ref-type="fn" rid="fn2">2</xref><xref ref-type="fn" rid="fn3">3</xref><xref ref-type="fn" rid="fn4">4</xref>
Authors: R C Burton, N L Warner
Journal: JNCI Journal of the National Cancer Institute (1980)

Cytotoxic T-lymphocytes (Tc) were induced in vitro to plasmacytoma tumor-associated antigens (TAA) by coculture of irradiated cells of plasma cell tumors (PCT) from NZB mice and viable nonimmune or PCT-immune spleen cells from NZB. (NZB X C57BL)F1, (NZB X B10.D2)F1, and (NZB X B10,BR)F1 mice. When nonimmune spleen cells were used, major histocompatibility complex (MHC)-linked genetic control of te primary in vitro induction of Tc to NZB PCT was demostrated for a shared TAA expressed on NZB and BALB/c PCT. Evidence was also obtained for a non-MHC-linked genetic control of the primary in vitro induction of Tc to a second TAA that ws expressed on both PCT and T-lymphomas. When the spleen cells were obtained from mice preimmunized to an NZB PCT, a secondary in vitro Tc response was observed, and a PCT-specific and strain-specific TAA or NZB mice was identified. In addition, results with the F1 hybrids also indicated an MHC-linked genetic control of the in vitro Tc response to this strain-specific TAA.
Allergic Rhinitis
Authors: Lisa M. Wheatley, Alkis Togias
Journal: New England Journal of Medicine (2015)

Allergic rhinitis is common and is often associated with asthma. Treatment includes intranasal glucocorticoids, oral and nasal antihistamines, leukotriene-receptor antagonists, and, when pharmacotherapy is not effective or produces unacceptable side effects, allergen immunotherapy.