tbuckley/cabot-search huggingface dataset:
Nebulised corticosteroids in the treatment of patients with asthma
Authors: J. M HILL
Journal: Thorax (1999)

Inhaled corticosteroids are the mainstay of anti-inflammatory treatment in patients with chronic asthma, and most patients’ symptoms are controlled by low or moderate doses of these agents. However, there are some patients with chronic severe asthma whose symptoms are inadequately controlled by high doses of inhaled corticosteroids and maximal bronchodilator therapy. Such patients require increasingly frequent courses of oral corticosteroids, often culminating in their long term use.

Until recently in the UK, budesonide (Pulmicort Respules, Astra Pharmaceuticals) was the only corticosteroid available for nebulisation. Fluticasone propionate (Flixotide Nebules, Glaxo Wellcome) was launched in late 1998, and is being actively marketed. The 1995 British Thoracic Society asthma guidelines state, however, that there are “. . . no published controlled trials of the effectiveness of nebulised budesonide in adults”.1 This review aims to address whether these guidelines hold true, or whether new evidence has emerged which should lead us to review this policy.

The evidence for the effectiveness of nebulised corticosteroids in the treatment of stable asthma is reviewed, together with a discussion of whether there is any evidence that their use allows a reduction in regular oral corticosteroid dose in patients with severe asthma. In considering this evidence it is important to compare the side effects of nebulised corticosteroids with those of high dose inhaled corticosteroids and with those of oral corticosteroids. Studies which compare nebulised corticosteroid with oral corticosteroid in the treatment of acute exacerbations of asthma are also reviewed. It is important to consider patient preference for nebulised, inhaled or oral therapy, which is closely linked with compliance with treatment. Finally, in such a review it is vital to consider the cost implications of any change in practice in the treatment of patients with acute and chronic asthma.

There are a large number of case reports and uncontrolled …
Factors affecting the absorption of vitamin K-1 in vitro.
Authors: D Hollander, E Rim
Journal: Gut (1976)

Factors which might affect the absorption of vitamin K of dietary origin were investigated using everted small bowel sacs. Increasing the bile salt concentration to 20 mM or the addition of long chain fatty acids, monoolein, or lecithin all resulted in significant (P less than 0-05) decrease in the absorption rate of the vitamin. The addition of 2-5 mM short and medium chain fatty acids did not change the absorption rate of vitamin K-1 (P greater than 0-05). The absorption rate of vitamin K-1 appears to be modified by the presence of compounds in the incubation medium which either alter the partition of the vitamin between the micelle and the cell membrane or which change the permeation characteristics of the compound through the unstirred water layer or modify the physical characteristics of the cell membrane itself. It is possible that some of the above factors modify the absorption of lipid soluble compounds in general.
SpliceArray Profiling of Breast Cancer Reveals a Novel Variant of <i>NCOR2/SMRT</i> That Is Associated with Tamoxifen Resistance and Control of <i>ERα</i> Transcriptional Activity
Authors: Luduo Zhang, Chun Gong, Samantha L.Y. Lau, Nan Yang, Oscar G.W. Wong, Annie N.Y. Cheung, Janice W.H. Tsang, Kelvin Y.K. Chan, Ui-Soon Khoo
Journal: Cancer Research (2012)

Abstract Gene expression profiling aimed at classifying and prognosing breast cancer has yielded signatures with little, if any, concordance. However, expression arrays used in these studies do not discriminate alternate RNA splice isoforms that vary widely in cancer and may resolve this problem. In this study, we profiled splice isoforms in a panel of tamoxifen-sensitive and -resistant cell lines, defining a novel variant (BQ323636.1) of the nuclear receptor corepressor 2 (NCOR2) that was associated with tamoxifen resistance. Overexpression of this variant in a tamoxifen-sensitive cell line induced its resistance to tamoxifen. We confirmed our initial findings from cell lines in 77 breast tumors from a Chinese cohort, where BQ323636.1 expression was higher in tamoxifen-resistant patients than tamoxifen-sensitive patients. For patients who were estrogen receptor (ER)-positive and had received tamoxifen treatment, higher BQ323636.1 expression level correlated with distant metastasis. High expression level of BQ323636.1 was found to be associated with poorer overall and disease-free survival for patients who had received tamoxifen treatment. Notably, higher BQ323636.1 versus NCOR2 wild-type ratio was also associated with negative ER and progesterone receptor (PR) status, and triple-negative status (ER−/PR−/HER2− receptor status). Mechanistic investigations showed that under conditions of tamoxifen exposure, BQ323636.1 suppressed the transcriptional activity of ERα, exhibiting promoter-regulating functions. Our findings highlight a novel splice variant of the ERα corepressor NCOR2 as a candidate biomarker in breast cancer that not only predicts tamoxifen response but may be targeted to overcome tamoxifen resistance. Cancer Res; 73(1); 246–55. ©2012 AACR.
Clinical Lecture ON ACUTE PNEUMONIA IN CHILDREN
Authors: H. M. Murray
Journal: BMJ (1907)

GENTLEMEN,-In dealing with this subject on the present occasion I propose to arrange my remarks in three groups.The first will deal with the value of a continuous record of the respiration-rate, with illustrative cases.In the second I shall show grounds for my disbelief in the utility of the current classifications of the disease, and, indeed, of any known classification, so far as prognosis and treatment are cancerned.The third group will contain a statement of my own experience concerning the complications, diagnosis, prognosis, and treatment of the disease. I. RESPIRATION-RATE.The frequency of respiration does not, in my judgement, receive the amount of consideration it deserves.In the case of young children suffering from acute disease of the lungs it is, I believe, of more importance to keep an accurate record of the respiration-rate than -of the frequency of the pulse.The normal respiration-rate varies with age.In healthy infants of 6 months of age, while sleeping or lying quietly in bed, it varies from 30 to 25, and in children of 3 years of age from 25 to 20.When respiration is disturbed by disease, the influence of age is more easily noticed, both as regards the rapidity of breathing and the constancy of the rate.Thus, a respiration-rate of 60 in a child of 3 years of age is of less favourable omen than a rate of 80 in a child of 6 months.In every case a knowledge of the course of the respirationrate is of more importance than a knowledge of the actual frequency at any one time.An increase in the respiration-rate depends upon many factors besides that of age.To some extent it generally increases in proportion to the nature and intensity of the febrile process.The varying influence of this factor renders it probable that it is the action of the toxines rather than the height or duration of the fever which is primarily responsible.It also depends on the extent of
Management and survival of patients with lung cancer in Scotland diagnosed in 1995: results of a national population based study
Authors: A Gregor
Journal: Thorax (2001)

The prognosis of patients with lung cancer in Scotland is poor and not improving. This study was designed to document factors influencing referral, diagnostic evaluation, treatment, and survival in patients with lung cancer.Patients diagnosed during 1995 were identified from the Scottish Cancer Registry and their medical records were reviewed. Adequate records were available in 91.2% of all potentially eligible cases.In 1995, patients in Scotland with lung cancer had a high rate of microscopic verification (74.1%) and 75.3% were assessed by a respiratory physician; however, only 56.8% received active treatment (resection 10.7%, radiotherapy 35.8%, chemotherapy 16.1%) and 2.9% participated in a clinical trial. Survival was poor with a median of 3.6 months; 21.1% (95% CI 19.8% to 22.4%) were alive at 1 year and 7.0% (95% CI 6.2% to 7.8%) at 3 years. Management by respiratory physician, oncologist, or thoracic surgeon was an independent predictor of access to potentially curative treatment and better survival.This national population based study demonstrates low use of treatment, poor survival, and the influence of process of care on survival. Implementation of evidence-based guidelines will require substantial changes in practice. Increasing the number of patients who receive treatment may improve survival.
A high density physical map of chromosome 1BL supports evolutionary studies, map-based cloning and sequencing in wheat
Authors: Romain Philippe, Etienne Paux, Isabelle Bertin, Pierre Sourdille, Fréderic Choulet, Christel Laugier, Hana Šimková, Jan Šafář, Arnaud Bellec, Sonia Vautrin, Zeev Frenkel, Federica Cattonaro, Federica Magni, Simone Scalabrin, Mihaela M Martis, Klaus FX Mayer, Abraham Korol, Hélène Bergès, Jaroslav Doležel, Catherine Feuillet
Journal: Genome biology (2013)

As for other major crops, achieving a complete wheat genome sequence is essential for the application of genomics to breeding new and improved varieties. To overcome the complexities of the large, highly repetitive and hexaploid wheat genome, the International Wheat Genome Sequencing Consortium established a chromosome-based strategy that was validated by the construction of the physical map of chromosome 3B. Here, we present improved strategies for the construction of highly integrated and ordered wheat physical maps, using chromosome 1BL as a template, and illustrate their potential for evolutionary studies and map-based cloning.Using a combination of novel high throughput marker assays and an assembly program, we developed a high quality physical map representing 93% of wheat chromosome 1BL, anchored and ordered with 5,489 markers including 1,161 genes. Analysis of the gene space organization and evolution revealed that gene distribution and conservation along the chromosome results from the superimposition of the ancestral grass and recent wheat evolutionary patterns, leading to a peak of synteny in the central part of the chromosome arm and an increased density of non-collinear genes towards the telomere. With a density of about 11 markers per Mb, the 1BL physical map provides 916 markers, including 193 genes, for fine mapping the 40 QTLs mapped on this chromosome.Here, we demonstrate that high marker density physical maps can be developed in complex genomes such as wheat to accelerate map-based cloning, gain new insights into genome evolution, and provide a foundation for reference sequencing.
Lower limb enthesopathy in patients with psoriasis without clinical signs of arthropathy: a hospital-based case-control study
Authors: P Gisondi, I Tinazzi, G El-Dalati, M Gallo, D Biasi, L M Barbara, G Girolomoni
Journal: Annals of the Rheumatic Diseases (2007)

Psoriasis is associated with a form of spondyloarthropathy in 10-30% of cases. A major feature of psoriatic arthritis is enthesitis. In some patients with psoriasis the presence of enthesitis could be underdiagnosed.To investigate the presence of lower limbs entheseal abnormalities in patients with chronic plaque psoriasis without signs and symptoms of psoriatic arthritis.Thirty patients with psoriasis and 30 controls underwent ultrasonographic evaluation of Achilles, quadriceps, patellar entheses and plantar aponeurosis. Ultrasonographic findings were scored according to the Glasgow Ultrasound Enthesitis Scoring System (GUESS).Mean GUESS score was significantly higher in patients with psoriasis as compared with controls: 7.9 (0.6) vs 2.9 (0.3); p<0.0001. In particular, the thickness of all tendons examined was significant higher in cases than in controls (p<0.0001), as well as the number of enthesophytes in all sites examined. In both cases and controls, the GUESS score was directly correlated with age (r = 0.22; p = 0.008), body mass index (r = 0.23, p = 0.0067) and waist circumference (r = 0.17; p = 0.02). In contrast, the GUESS score was not correlated with the duration and severity of psoriasis according to the Psoriasis Area and Severity Index (r = 0.03; p = 0.8) and body surface area involvement (r = 0.07; p = 0.6).Entheseal abnormalities can be documented by ultrasonography in clinically asymptomatic patients with psoriasis. These findings could be related to a subclinical entheseal psoriatic inflammation. We suggest close follow-up of patients with psoriasis with entheseal abnormalities for early diagnosis of psoriatic arthritis.
Alcohol consumption as a preventive factor for developing rheumatoid arthritis: a dose-response meta-analysis of prospective studies
Authors: Zhichao Jin, Chun Xiang, Qing Cai, Xin Wei, Jia He
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objective</h3> To summarise the evidence regarding the dose-response association between alcohol consumption and risk of rheumatoid arthritis (RA). <h3>Method</h3> Studies were identified from search of MEDLINE, Embase and Web of Science databases between 1 January 1946 and 10 April 2013, and from review of the conference abstracts and the reference lists of retrieved articles. Prospective studies that reported relative risks (RRs) with 95% CIs for the association between alcohol consumption and the risk of RA were included. Results from individual studies were pooled using a dose-response meta-analysis. <h3>Results</h3> Up to 10 April 2013, 8 prospective studies contained 195 029 participants and 1878 RA cases were included. The results indicated that low to moderate alcohol consumption yielded a preventive effect on RA development (RR: 0.86; 95% CI 0.78 to 0.94), and provided some evidence of a non-linear relationship between alcohol consumption and risk of RA. Dose-response meta-analysis of the study data revealed that compared with that for no alcohol consumption, the adjusted RR was 0.93 (95% CI 0.88 to 0.98) for 3 g/day of alcohol consumption, 0.86 (95% CI 0.76 to 0.97) for 9 g/day, 0.88 (95% CI 0.78 to 0.99) for 12 g/day, 0.91 (95% CI 0.81 to 1.03) for 15 g/day, and 1.28 (95% CI 0.94 to 1.73) for 30 g/day. Subgroup analysis indicated that women who had low to moderate alcohol consumption had a 19% reduction in RA risk. Regardless of sex, a consistent low to moderate alcohol consumption for a period of at least 10 years was found to have a 17% reduction in RA risk. <h3>Conclusions</h3> Low to moderate alcohol consumption inversely associated with the development of RA in a manner that appears to be dose-dependent, time-dependent and sex-dependent. Large prospective studies that investigate gene-environment interactions are required to further clarify the aetiology of RA.
Gene Expression Signature in Advanced Colorectal Cancer Patients Select Drugs and Response for the Use of Leucovorin, Fluorouracil, and Irinotecan
Authors: Maguy Del Rio, Franck Molina, Caroline Bascoul-Mollevi, Virginie Copois, Frédéric Bibeau, Patrick Chalbos, Corinne Bareil, Andrew Kramar, Nicolas Salvetat, Caroline Fraslon, Emmanuel Conseiller, Virginie Granci, Benjamin Leblanc, Bernard Pau, Pierre Martineau, Marc Ychou
Journal: Journal of Clinical Oncology (2007)

Purpose In patients with advanced colorectal cancer, leucovorin, fluorouracil, and irinotecan (FOLFIRI) is considered as one of the reference first-line treatments. However, only about half of treated patients respond to this regimen, and there is no clinically useful marker that predicts response. A major clinical challenge is to identify the subset of patients who could benefit from this chemotherapy. We aimed to identify a gene expression profile in primary colon cancer tissue that could predict chemotherapy response. Patients and Methods Tumor colon samples from 21 patients with advanced colorectal cancer were analyzed for gene expression profiling using Human Genome GeneChip arrays U133. At the end of the first-line treatment, the best observed response, according to WHO criteria, was used to define the responders and nonresponders. Discriminatory genes were first selected by the significance analysis of microarrays algorithm and the area under the receiver operating characteristic curve. A predictor classifier was then constructed using support vector machines. Finally, leave-one-out cross validation was used to estimate the performance and the accuracy of the output class prediction rule. Results We determined a set of 14 predictor genes of response to FOLFIRI. Nine of nine responders (100% specificity) and 11 of 12 nonresponders (92% sensitivity) were classified correctly, for an overall accuracy of 95%. Conclusion After validation in an independent cohort of patients, our gene signature could be used as a decision tool to assist oncologists in selecting colorectal cancer patients who could benefit from FOLFIRI chemotherapy, both in the adjuvant and the first-line metastatic setting.
Effect of ADRB2 polymorphisms on the efficacy of salmeterol and tiotropium in preventing COPD exacerbations: a prespecified substudy of the POET-COPD trial
Authors: Klaus F Rabe, Leonardo M Fabbri, Elliot Israel, Harald Kögler, Kathrin Riemann, Hendrik Schmidt, Thomas Glaab, Claus F Vogelmeier
Journal: The Lancet Respiratory Medicine (2013)
Induction of Vascular Endothelial Growth Factor in Balloon-Injured Baboon Arteries
Authors: Johannes Ruef, Zhao Y. Hu, Li-Yan Yin, Yaxu Wu, Stephen R. Hanson, Andrew B. Kelly, Laurence A. Harker, Gadiparthi N. Rao, Marschall S. Runge, Cam Patterson
Journal: Circulation Research (1997)

Abstract Neovascularization is a hallmark of neointimal formation in atherosclerotic plaques and restenotic lesions. Vascular endothelial growth factor (VEGF) promotes neovascular growth, whereas oxidative stress is a potent factor in vascular cell proliferation. To investigate the mechanisms of neovascular formation, we treated human and rat vascular smooth muscle cells (VSMCs) with H 2 O 2 . Northern blot analysis demonstrated a dose- and time-dependent increase in VEGF mRNA, with a maximum of 4-fold at 3 hours (200 μmol/L). As determined by immunoblotting and enzyme-linked immunosorbent assay, VEGF protein expression and secretion were similarly increased. Human umbilical vein endothelial cells were treated with conditioned medium from VSMCs incubated with 200 μmol/L H 2 O 2 . DNA synthesis, measured by thymidine incorporation, was increased 4-fold compared with control, an effect that was blocked by a neutralizing anti-VEGF antibody. The lipid peroxidation product 4-hydroxynonenal (1 μmol/L), an endogenous reactive oxygen species present in human atherosclerotic lesions, also increased VEGF secretion in VSMCs in a similar time-dependent fashion. Immunohistochemical staining and in situ hybridization of aortic sections from balloon-injured baboons demonstrated increased VEGF expression in discrete areas of the neointima and media compared with control sections, and expression correlated with the generation of 4-hydroxynonenal. Regulators of VEGF expression, such as reactive oxygen species, may enhance neovascularization of atherosclerotic and restenotic arteries.
A Case of Amaursis Fugax
Authors: C. E. Glascott
Journal: BMJ (1879)

UUIY I9, I879.doing all in as short a time as possible, that he "might get a few minutes' smoke" at the ladder-foot before his next journey up.More than once, too, he has foolishly tried with how heavy a weight he could climb, and has been "brought to" before getting to the top.Then his master also vends beer, and again the patient's physical
Where Is the Evidence That the Resurgence of Nomograms Is Harmful?
Authors: Samuel H. Zwillich
Journal: Annals of Internal Medicine (2009)

Letters17 February 2009Where Is the Evidence That the Resurgence of Nomograms Is Harmful?Samuel H. Zwillich, MDSamuel H. Zwillich, MDFrom East Lyme, CT 06333.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-150-4-200902170-00016 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The review by Grimes (1) of the history of nomograms was informative. However, his criticism of the “epidemic” of nomogram resurgence was fundamentally unsubstantiated. Grimes states that “nomograms provided speed in calculation at the cost of precision” without providing any evidence that the lost precision mattered. Where is the evidence, for example, that calculating likelihood ratios to additional decimal places improves clinical decision making? Conversely, where is the evidence that calculating medication doses by using a body surface area nomogram adversely affects patient well-being?An alternative, testable hypothesis is that contemporary reliance on computer-generated values numbs physicians ...Reference1. Grimes DA. The nomogram epidemic: resurgence of a medical relic. Ann Intern Med. 2008;149:273-5. [PMID: 18711159] LinkGoogle Scholar Author, Article, and Disclosure InformationAuthors: Samuel H. Zwillich, MDAffiliations: From East Lyme, CT 06333.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoThe Nomogram Epidemic: Resurgence of a Medical Relic David A. Grimes Where Is the Evidence That the Resurgence of Nomograms Is Harmful? David A. Grimes Metrics Cited byUsing Nomograms to Reduce Harm from Clinical Calculations 17 February 2009Volume 150, Issue 4Page: 282KeywordsBody surface areaComputersConflicts of interestDecision makingLikelihood ratio ePublished: 17 February 2009 Issue Published: 17 February 2009 Copyright & PermissionsCopyright © 2009 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Combined<i>Haemophilus influenzae</i>respiratory infection and allergic airways disease drives chronic infection and features of neutrophilic asthma
Authors: Ama-Tawiah Essilfie, Jodie L Simpson, Margaret L Dunkley, Lucy C Morgan, Brian G Oliver, Peter G Gibson, Paul S Foster, Philip M Hansbro
Journal: Thorax (2012)

<h3>Background</h3> 20–30% of patients with asthma have neutrophilic airway inflammation and reduced responsiveness to steroid therapy. They often have chronic airway bacterial colonisation and <i>Haemophilus influenzae</i> is one of the most commonly isolated bacteria. The relationship between chronic airway colonisation and the development of steroid-resistant neutrophilic asthma is unclear. <h3>Objectives</h3> To investigate the relationship between <i>H influenzae</i> respiratory infection and neutrophilic asthma using mouse models of infection and ovalbumin (OVA)-induced allergic airways disease. <h3>Methods</h3> BALB/c mice were intratracheally infected with <i>H influenzae</i> (day 10), intraperitoneally sensitised (day 0) and intranasally challenged (day 12–15) with OVA. Treatment groups were administered dexamethasone intranasally during OVA challenge. Infection, allergic airways disease, steroid sensitivity and immune responses were assessed (days 11, 16 and 21). <h3>Results</h3> The combination of <i>H influenzae</i> infection and allergic airways disease resulted in chronic lung infection that was detected on days 11, 16 and 21 (21, 26 and 31 days after infection). Neutrophilic allergic airways disease and T helper 17 cell development were induced, which did not require active infection. Importantly, all features of neutrophilic allergic airways disease were steroid resistant. Toll-like receptor 4 expression and activation of phagocytes was reduced, but most significantly the influx and/or development of phagocytosing neutrophils and macrophages into the airways was inhibited. <h3>Conclusions</h3> The combination of infection and allergic airways disease promotes bacterial persistence, leading to the development of a phenotype similar to steroid-resistant neutrophilic asthma and which may result from dysfunction in innate immune cells. This indicates that targeting bacterial infection in steroid-resistant asthma may have therapeutic benefit.