tbuckley/cabot-search huggingface dataset:
Principles and Practice of Pulmonary Rehabilitation
Journal: Thorax (1994)

Book notices 91% (compared with 87% for the whole group).The logic behind their supposition that the accuracy of high resolution CT scanning would be diminished if only applied to cases which are biopsy proven is not clear.They might have supposed that only cases with atypical clinical presentation or radiographic features were confirmed by biopsy (in our practice some patients with typical fibrosing alveolitis may undergo biopsy for the evalu- ation of disease activity).In any event, we can dismiss the suggestion that including "biopsy unproven" cases in our study resulted in an overstatement of the accuracy of high resolution CT scanning in making the diagnosis of fibrosing alveolitis.
Diagnostic test allergens used for <i>in vivo</i> diagnosis of allergic diseases are at risk: a European Perspective
Authors: L. Klimek, H. J. Hoffmann, H. Renz, P. Demoly, T. Werfel, P. M. Matricardi, A. Muraro, P. Schmid‐Grendelmeier, V. Cardona, N. G. Papadopoulos
Journal: Allergy (2015)

In the European Union (EU), allergens used for diagnostic tests (TAs) are defined as medicinal products and have to be registered by national authorities. The current situation is not homogeneous. Existing authorizations need to be kept in the market in some EU states, while others need complete new authorizations requiring clinical trials, quality assurance methods, stability studies, and periodic safety update reports. Allergen manufacturers argue that offering a comprehensive panel of TAs may be economically disastrous. Expenses for initiation and maintenance of TA authorizations far exceed their related revenues and manufacturers may be forced to significantly limit their allergen portfolios. The availability of a wide range of high-quality TAs is very important for in vivo diagnoses of IgE-mediated allergies. Increased regulatory demands induce costs that need to be covered by public health organizations or reimbursed by health insurance companies.
Abstract 16496: Electronegative Low-Density Lipoprotein of Metabolic Syndrome Patients Induces Release of Inflammatory Adipocytokines and Accumulation of M1 Macrophages in Adipose Tissue
Authors: Chih-Sheng Chu, Hua-Chen Chan, Liang-Yin Ke, Hsiu-Chuan Chan, Chung-Ya Wang, Kai-Hung Cheng, Jonathan Lu, Hsiang-Chun Lee, Hsuan-Fu Kuo, Ching-Tang Chang, Sheng-Hsiung Sheu, Tatsuya Sawamura, Wen-Ter Lai, Chu-Huang Chen
Journal: Circulation (2014)

Background: Inflammation-associated dysfunction of adipocytes plays an etiologic role in insulin resistance and diabetes development. To delineate the mechanism, we examined the in vivo and in vitro effects LDL of metabolic syndrome (MetS) patients on adipose tissue.

Methods and Results: Plasma LDL was isolated from MetS patients and healthy control subjects with similar LDL cholesterol levels (142.2±41.8 vs. 140.9±44.5 mg/dL; n=29 each). Anion-exchange chromatography showed that MetS LDL contained a higher percentage of the most electronegative subfraction, L5, than control LDL (5.3±4.9% vs. 2.1±1.4%; P <0.001). Tail-vein injections of human L5 but not the least electronegative L1 (n=5 each, 3 mg/kg/day x 4 weeks) into wild type C57BL/6 mice induced accumulation of F4/80+/CD11c+ M1 macrophages, with adjacent apoptotic adipocytes, in the adipose tissue (Figure, Panel A). L5 signals through lectin-like oxidized LDL receptor-1 (LOX-1). Treating human adipocytes with L5 but not L1 induced release of inflammatory adipocytokines (IL-6, IL-8, CXCL10, RANTES) and complement (C5/C5a) into the culture-conditioned medium (CCM); neutralizing LOX-1 attenuated the release (Figure, Panel B). Incubating human THP-1 monocytes with L5-CCM resulted in a 300 fold enhancement of transwell migration in 24 hours, when compared with incubating the cells with L1-CCM (n=6; P <0.001). Migrated cells exhibited positive macrophage marker PM-2K, indicating transformation of monocytes into macrophages induced by the L5-CCM.

Conclusions: L5 induces macrophage transformation from monocytes via releasing inflammatory cytokines from adipocytes; aggregation of M1 macrophages in the adipose tissue further worsens adipocytic dysfunction. Thus, increased LDL electronegativity may be a predisposing factor for diabetes in MetS.

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Abstract 1934: Improved deconvolution of heterogeneous tumor data to reconstruct clonal evolution from bulk genomic samples
Authors: Theodore Roman, Russell Schwartz
Journal: Cancer Research (2015)

Abstract Intratumor heterogeneity has long been a confounding factor in interpreting cancer genomic data, but has also been useful in reconstructing progression processes based on variation between clonal populations in single tumors. We previously developed a strategy of applying computational deconvolution algorithms to gene expression or DNA copy number data to reconstruct models of progression of cell populations from bulk tumor samples. Many tools have since been proposed for similar deconvolution analysis, but all are limited by the computational difficulty of unambiguously distinguishing small cell populations and variants from noise in genomic assays. We present a novel approach to infer tumor progression pathways from deconvolved genomic data designed to leverage the fact that tumors that partition into subtypes with similar evolutionary trajectories would be expected to lead to a mathematical substructure in the genomic data, known as a simplicial complex, which can be modeled computationally to better deconvolve cell populations across tumor types. We have developed a computational pipeline to perform tumor deconvolution while taking into consideration this kind of mathematical structure. The pipeline clusters tumors to identify genetically distinct subgroups, fits mixture models to these subgroups, and uses overlap between them to infer a refined deconvolution of major cellular populations and possible pathways of progression between them. We apply our methods to a set of RNASeq data from the TCGA breast cancer data set and to synthetic data modeling distinct scenarios of tumor progression. We first compare our methods on the synthetic data to our earlier work and to a comparative Gaussian mixture model. All methods perform comparably on unstructured data but the new method substantially outperforms the others on data consistent with simple scenarios for tumor progression along multiple discrete subtypes. The novel method, however, shows lower tolerance for noisy data than a Gaussian mixture model. Application to the TCGA RNASeq data showed our method could partition tumors into discrete subcategories associated with HER2+, ER/PR+, and triple-negative status and could exploit the resulting substructure of the data to deconvolve tumor data and infer progression models reflecting partial sharing of progression states between subtypes. Gene enrichment analysis showed association of deconvolved cell populations with a variety of gene functional categories suggestive of distinct progression mechanisms of the subtypes. Citation Format: Theodore Roman, Russell Schwartz. Improved deconvolution of heterogeneous tumor data to reconstruct clonal evolution from bulk genomic samples. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1934. doi:10.1158/1538-7445.AM2015-1934
Future directions for geriatric medicine
Authors: J. Young
Journal: BMJ (2000)

Less than 50 years ago the plight of sick older people in the United Kingdom was pitiful. Chronically sick old people were left to languish bedridden in the most miserable of circumstances. The specialty of geriatric medicine developed in the 1950s as a response to the particular health needs of frail older people.1 Timely response to crises, comprehensive assessment of needs, multidisciplinary management focused on reducing disability, and helping older people to remain at home while recognising the needs of family carers became the underlying principles. These elements have become accepted and implemented in many countries, with convincing evidence of effectiveness.2 Britain is still unique, however, in the extent to which geriatricians work in the acute hospital sector, and a major triumph of elderly care medicine has been the unquestioned access of acutely ill older people to district general hospitals. With these successes it is therefore surprising that geriatric medicine is now …
Unlicensed and off label drug use for paediatric patients
Authors: R. M Martin, L. V Wilton, R. D Mann, P. Steventon, S. R Hilton, S. Conroy
Journal: BMJ (1998)

Editor—Turner et al highlight the fact that children admitted to hospital are often prescribed unlicensed drugs and drugs given outside the terms of their product licence (off label).1 The appropriateness of such prescribing is uncertain, and a high rate of adverse drug reactions has been observed in children prescribed such drugs.2 The problem is not limited to hospitals. General practitioners may be asked to prescribe unlicensed or off label drugs by specialists or may consider initiating such treatment themselves. Little information exists on the extent of such prescribing in primary care. 

We examined the prescribing of selective serotonin reuptake inhibitors to children in general practice by accessing a computerised database of 100 British general practices (349 doctors) using the AAH Meditel System 5 computer system to enter medical records (Doctors Independent Network).3 We determined the number of children aged 12 and under who had at least one prescription for a selective serotonin reuptake inhibitor between January 1992 and December 1996. For each child we ascertained age at first prescription; sex; name, dose, and formulation of the drug; number of prescriptions issued during the study; and reason for prescription. To be certain that we had identified children, we included only subjects who had an immunisation record in their notes, with dates consistent with their recorded age. 

Overall we identified 25 children who met the entry criteria for the study, except that we had to exclude six because of doubt over their age. The table shows the reasons for the prescription of the drugs. The commonest antidepressant prescribed was fluoxetine capsules. The British National Formulary states that prescribing these drugs for children is not recommended. 

These data from a small number of practices (under 1% of all British practices) suggest that nationally there are probably hundreds of children who have been prescribed off label antidepressants in general practice. Research suggests that some children are prescribed these drugs in general practice soon after their launch, when clinical experience is limited.4 We agree with Turner et al that all drugs used to treat children should be evaluated for their paediatric efficacy, safety, and quality. Doctors should have enough information to be able to discuss with parents the likely benefits and risks of using these drugs.5 Research should also assess the appropriateness of such prescribing in general practice.
FIBRILLATION NUMBER BASED ON WAVELENGTH AND CRITICAL MASS IN PATIENTS WHO UNDERWENT RADIOFREQUENCY CATHETER ABLATION FOR ATRIAL FIBRILLATION
Authors: Minki Hwang, Junbeom Park, Young-Seon Lee, Jae Hyung Park, Eun Bo Shim, Hui-Nam Pak
Journal: Journal of the American College of Cardiology (2015)
Genetic Dissection of Acute Anterior Uveitis Reveals Similarities and Differences in Associations Observed With Ankylosing Spondylitis
Authors: Philip C. Robinson, Theodora A. M. Claushuis, Adrian Cortes, Tammy M. Martin, David M. Evans, Paul Leo, Pamela Mukhopadhyay, Linda A. Bradbury, Katie Cremin, Jessica Harris, Walter P. Maksymowych, Robert D. Inman, Proton Rahman, Nigil Haroon, Lianne Gensler, Joseph E. Powell, Irene E. van der Horst‐Bruinsma, Alex W. Hewitt, Jamie E. Craig, Lyndell L. Lim, Denis Wakefield, Peter McCluskey, Valentina Voigt, Peter Fleming, Mariapia Degli‐Esposti, Jennifer J. Pointon, Michael H. Weisman, B. Paul Wordsworth, John D. Reveille, James T. Rosenbaum, Matthew A. Brown
Journal: Arthritis & Rheumatology (2014)

To use high-density genotyping to investigate the genetic associations of acute anterior uveitis (AAU) in patients with and those without ankylosing spondylitis (AS).We genotyped samples from 1,711 patients with AAU (either primary or combined with AS), 2,339 AS patients without AAU, and 10,000 control subjects on an Illumina Immunochip Infinium microarray. We also used data for AS patients from previous genome-wide association studies to investigate the AS risk locus ANTXR2 for its putative effect in AAU. ANTXR2 expression in mouse eyes was investigated by real-time quantitative reverse transcription-polymerase chain reaction.A comparison between all patients with AAU and healthy control subjects showed strong association over HLA-B, corresponding to the HLA-B27 tag single-nucleotide polymorphism rs116488202. The association of 3 non-major histocompatibility complex loci, IL23R, the intergenic region 2p15, and ERAP1, reached genome-wide significance (P < 5 × 10(-8)). Five loci harboring the immune-related genes IL10-IL19, IL18R1-IL1R1, IL6R, the chromosome 1q32 locus harboring KIF21B, as well as the eye-related gene EYS, were also associated, reaching a suggestive level of significance (P < 5 × 10(-6)). Several previously confirmed AS associations demonstrated significant differences in effect size between AS patients with AAU and AS patients without AAU. ANTXR2 expression varied across eye compartments.These findings of both novel AAU-specific associations and associations shared with AS demonstrate overlapping but also distinct genetic susceptibility loci for AAU and AS. The associations in IL10 and IL18R1 are shared with inflammatory bowel disease, suggesting common etiologic pathways.
Abstract 16144: The Impact of Ventricular Pacing for Elderly Patients With Pacemaker Implantation: Over One Decade and Large Cohort Analysis
Authors: Ayako Kamijima, Kohei Ishibashi, Mitsuru Wada, Ikutaro Nakajima, Koji Miyamoto, Hideo Okamura, Takashi Noda, Takeshi Aiba, Shiro Kamakura, Kengo Kusano
Journal: Circulation (2014)

Introduction: Previous studies showed that ventricular pacing (VP) increased the cardiac event of patients with pacemaker (PM). However, these studies consisted of patients under 75 years old and the influence of VP for elderly patients (over 75 years old) is still unclear. We sought to evaluate long-term effect of VP for elderly patients. Methods: A total of 782 patients (mean 57.2 years old) underwent PM implantation for brady-arrhythmia were enrolled from 1978 to 2005. The elderly patients (199 patients, over 75 years old, mean 80.7 years old) and all patients were divided into VP and non-VP group, and evaluated adverse events (death or readmission for heart failure). Results: The mean follow-up period was 10.1 years and 84 elderly patients (42%) developed adverse events. Kaplan-Meier analysis revealed that (1) VP increased the adverse event in all patients. (2) There was no significant difference in the adverse events of elderly patients between VP and non-VP group (Fig). Conclusion: VP may be tolerated for elderly patients with PM, whereas VP has no effect for the prognosis.
Study greatly underestimates the cost effectiveness of statin treatment
Authors: J J V McMurray, C E Morrison
Journal: BMJ (1996)

Cost effectiveness of lowering cholesterolCost consequence analysis may be more useful to decision makers EDrroR,-If economic analyses are to provide guidance on population health strategies they should consider all relevant costs and consequences associated with medical interventions.We have identified five methodological deficien- cies in the economic analysis of P D P Pharoah and W Hollingworth.'
Disruption of pulmonary lipid homeostasis drives cigarette smoke-induced lung inflammation in mice
Authors: Mathieu C. Morissette, Pamela Shen, Danya Thayaparan, Martin R. Stämpfli
Journal: European Respiratory Journal (2015)

Overwhelming evidence links inflammation to the pathogenesis of smoking-related pulmonary diseases, especially chronic obstructive pulmonary disease (COPD). Despite an increased understanding of the disease pathogenesis, mechanisms initiating smoking-induced inflammatory processes remain incompletely understood. To investigate the mechanisms that initiate and propagate smoke-induced inflammation, we used a well-characterised mouse model of cigarette smoke exposure, mice deficient for interleukin (IL)-1α, IL-1β and Toll-like receptor 4, and antibodies blocking granulocyte-macrophage colony-stimulating factor (GM-CSF). Studies were also pursued using intranasal delivery of human oxidised low-density lipoprotein (hOxLDL), a source of oxidised lipids, to investigate the inflammatory processes associated with impaired lipid homeostasis. We found that cigarette smoke exposure rapidly led to lipid accumulation in pulmonary macrophages, a defining feature of foam cells, which in turn released high levels of IL-1α. In smoke-exposed IL-1α-deficient mice, phospholipids accumulated in the bronchoalveolar lavage, a phenomenon also observed when blocking GM-CSF. Intranasal administration of hOxLDL led to lipid accumulation in macrophages and initiated an inflammatory process that mirrored the characteristics of cigarette smoke-induced inflammation. These findings identify a link between lipid accumulation in macrophages, inflammation and damaged surfactant, suggesting that the response to damaged pulmonary surfactant is a central mechanism that drives cigarette smoke-induced inflammation. Further investigations are required to explore the role of distorted lipid homeostasis in the pathogenesis of COPD.
STUDIES OF DIABETES MELLITUS
Authors: L. H. Newburgh, Dorothy S. Waller
Journal: Journal of Clinical Investigation (1932)

During the past several years a number of writers in this country and abroad have maintained that liberal additions, of carbohydrate to the diabetic diet, usually accompanied by significant reduction in the fat, do not cause glycosuria, nor require an increase in the amount of insulin.They attribute this beneficial outcome to a variety of factors -(1) the depressing effect of fat upon the utilization of glucose; (2) the stimulation of carbohydrate metabolism by ingested carbohydrate; (3) augmentation of the combustion of glucose brought about by under-nutrition; (4) and it is even suggested that the improvement is to be attributed to the in- creased activity of some hitherto unrecognized principle of nutrition brought to light by the high carbohydrate, low fat diet.It is, for example, stated by Gray and Sansum (1), "That whether the beneficial clinical results which have been obtained by using these diets (carbohydrate-rich, fat-poor) are due to the increase in the carbo- hydrates or the decrease in the fats, is still debatable."Rabinowitch (2) writes, " Experiences with it (the high carbohydrate, low calory diet) are inconsistent with our present concept of the metabolism of diabetes."sugar grams grams grams grams
Abstract A26: Analysis of ABCB1, ABCC1 and ABCG2 expression and clinical parameters in 40 primary retinoblastoma cases
Authors: Blanca Elena Castro, Eunice Aguilar, Lourdes Cabrera, Javier Camacho, Adriana Hernandez, Guillermo Ramón, Stanislaw Sadowinski, Manuela Orjuela, Veronica Ponce
Journal: Clinical Cancer Research (2015)

Abstract Multidrug resistance (MDR) is one of the most important mechanisms involved in chemotherapy failure in cancer. ABC transporters constitute a superfamily of pumps that efflux metabolites, xenobiotics and drugs outside the cell. In many types of malignant tumors some of these transporters are overexpressed causing MDR and consequently tumor progression. ABCB1, ABCC1 and ABCG2 are the ABC transporters whose overexpressions are most frequently involved in chemotherapy failure. Eventhough expression of these transporters has been well studied in many types of adult tumors, expression of ABC transporters and correlation with clinical features have been scarcely reported in retinoblastoma, and intraocular malignant tumor occurring in early infancy. Therefore our objective in this work was to determine ABCB1, ABCC1 and ABCG2 expression by qPCR in untreated primary retinoblastoma cases and to explore whether or not correlations with relevant clinical features do exist. Our results on RNA from 40 retinoblastoma cases naive to chemotherapy treatment, show high mRNA expression of ABCC1 followed by ABCB1 and marginal expression of ABCG2, these results are consistent with immunohistochemistry results from others. ABCC1 was found significantly more expressed in bilateral than unilateral cases. Citation Format: Blanca Elena Castro, Eunice Aguilar, Lourdes Cabrera, Javier Camacho, Adriana Hernandez, Guillermo Ramón, Stanislaw Sadowinski, Manuela Orjuela, Veronica Ponce. Analysis of ABCB1, ABCC1 and ABCG2 expression and clinical parameters in 40 primary retinoblastoma cases. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Drug Sensitivity and Resistance: Improving Cancer Therapy; Jun 18-21, 2014; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(4 Suppl): Abstract nr A26.
Local research ethics committees should review their approval of prevention trial
Authors: C. Read
Journal: BMJ (1996)

EDITOR,—R D Bulbrook's editorial discusses who should take tamoxifen and for how long.1 The British aTTom (adjuvant tamoxifen treatment offer more) trial aims to recruit up to 20000 women with primary breast cancer. Many of these women could receive at least seven years' treatment with tamoxifen—two years more than the National Cancer Institute considers routinely advisable for …
Upregulation of MMP-2 &amp; 9 by Co-Culture of Human Myeloma Cell Lines and Endothelial Cells May Be Responsible for Protection Against Cytotoxic Drugs.
Authors: Shankaranarayana Paneesha, Raghu Adya, Hemali Khanji, Ed Leung, C. Vijayasekar, Guy Pratt, Anton Borg, Peter Rose, Alan Morris
Journal: Blood (2006)
Non-Alcoholic Steatohepatitis: Limited Available Treatment Options but Promising Drugs in Development and Recent Progress Towards a Regulatory Approval Pathway
Authors: Claudia Filozof, Barry J. Goldstein, Richard N. Williams, Arun Sanyal
Journal: Drugs (2015)

The prevalence of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) is increasing world-wide in parallel to the increase of the obesity epidemic. Insulin resistance (IR) and the accumulation of triglyceride-derived toxic lipid metabolites play a key role in its pathogenesis. Multiple biomarkers are being evaluated for the non-invasive diagnosis of NASH. However, a percutaneous liver biopsy is still the gold standard method; the minimal diagnostic criteria include the presence of >5% macrovesicular steatosis, inflammation, and liver cell ballooning. Several pharmaceutical agents have been evaluated for the treatment of NASH; however, no single therapy has been approved so far. Due to the increasing prevalence and the health burden, there is a high need to develop therapeutic strategies for patients with NASH targeting both those with early-stage disease as well as those with advanced liver fibrosis. There are unique challenges in the design of studies for these target populations. Collaborative efforts of health authorities, medical disease experts, and the pharmaceutical industry are ongoing to align options for a registrational pathway. Several companies pursuing different mechanisms of action are nearing the end of phase II with their candidates. This manuscript reviews those compounds with a variety of mode of actions that have been evaluated and/or are currently being tested with the goal of achieving a NAFLD/NASH indication.
Oseltamivir-resistant 2009–2010 pandemic influenza A (H1N1) in an immunocompromised patient
Authors: P.A Chan, N.T Connell, A.M Gabonay, B. Westley, J.M Larkin, S.P LaRosa, K. Chapin, L. Mermel
Journal: Clinical Microbiology and Infection (2010)