tbuckley/cabot-search huggingface dataset:
Not every cell is as it seems: a role for ductular epithelial cells in fibrosis?
Authors: E. E. Powell, J. R. Jonsson, A. D. Clouston
Journal: Gut (2010)

A ductular reaction at the periphery of portal tracts appears to be a common stereotypical response to injury that is observed in a number of chronic liver diseases, including viral hepatitis. It consists of a complex of strings of cholangiocytes, small bile ductules, stroma and inflammatory cells, and occurs at the interface between portal tracts and parenchyma.1 These reactive ductules are postulated to arise from hepatic progenitor cells, small bipotential cells capable of proliferation and differentiation into both hepatocytes and cholangiocytes. This alternative pathway of liver regeneration is activated when mature hepatocytes are unable to proliferate sufficiently to replace lost cells.2 Ductules are rarely seen in normal human liver,3 but increase in number in association with the severity of liver injury. Studies in chronic viral hepatitis, haemochromatosis, and alcoholic and non-alcoholic liver disease have shown a close correlation between progenitor cell expansion and the extent of hepatocellular injury, inflammation or fibrosis, although cause and effect has not been determined.4–7

The study of Svegliati-Baroni and colleagues8 in this issue of Gut ( see page 108 ) demonstrates a significant association between reactive ductular cells, hepatic progenitor cells and stage of fibrosis in patients with chronic hepatitis C virus (HCV) infection, further supporting these earlier studies. Interestingly the current study also …
Whole-genome sequence variation, population structure and demographic history of the Dutch population
Authors: Laurent C. Francioli, Androniki Menelaou, Sara L. Pulit, Freerk van Dijk, Pier Francesco Palamara, Clara C. Elbers, Pieter B. T. Neerincx, Kai Ye, Victor Guryev, Wigard P. Kloosterman, Patrick Deelen, Abdel Abdellaoui, Elisabeth M. van Leeuwen, Mannis van Oven, Martijn Vermaat, Mingkun Li, Jeroen F. J. Laros, Lennart C. Karssen, Alexandros Kanterakis, Najaf Amin, Jouke Jan Hottenga, Eric-Wubbo Lameijer, Mathijs Kattenberg, Martijn Dijkstra, Heorhiy Byelas, Jessica van Setten, Barbera D. C. van Schaik, Jan Bot, Isaäc J. Nijman, Ivo Renkens, Tobias Marschall, Alexander Schönhuth, Jayne Y. Hehir-Kwa, Robert E. Handsaker, Paz Polak, Mashaal Sohail, Dana Vuzman, Fereydoun Hormozdiari, David van Enckevort, Hailiang Mei, Vyacheslav Koval, Matthijs H. Moed, K Joeri van der Velde, Fernando Rivadeneira, Karol Estrada, Carolina Medina-Gomez, Aaron Isaacs, Steven A. McCarroll, Marian Beekman, Anton J. M. de Craen, H. Eka D. Suchiman, Albert Hofman, Ben Oostra, André G. Uitterlinden, Gonneke Willemsen, Mathieu Platteel, Jan H. Veldink, Leonard H. van den Berg, Steven J. Pitts, Shobha Potluri, Purnima Sundar, David R. Cox, Shamil R. Sunyaev, Johan T. den Dunnen, Mark Stoneking, Peter de Knijff, Manfred Kayser, Qibin Li, Yingrui Li, Yuanping Du, Ruoyan Chen, Hongzhi Cao, Ning Li, Sujie Cao, Jun Wang, Jasper A. Bovenberg, Itsik Pe'er, P Eline Slagboom, Cornelia M. van Duijn, Dorret I. Boomsma, Gert-Jan B. van Ommen, Paul I. W. de Bakker, Morris A. Swertz, Cisca Wijmenga
Journal: Nature Genetics (2014)
Randomized, Placebo-Controlled Study of Oregovomab for Consolidation of Clinical Remission in Patients With Advanced Ovarian Cancer
Authors: Jonathan S. Berek, Peyton T. Taylor, Alan Gordon, Mary J. Cunningham, Neil Finkler, James Orr, Saul Rivkin, Birgit C. Schultes, Theresa L. Whiteside, Christopher F. Nicodemus
Journal: Journal of Clinical Oncology (2004)

To assess oregovomab as consolidation treatment of advanced ovarian cancer and refine the immunotherapeutic strategy for subsequent study.Patients with stage III/IV ovarian cancer who had a complete clinical response to primary treatment were randomly assigned to oregovomab or placebo administered at weeks 0, 4, and 8, and every 12 weeks up to 2 years or until recurrence. The primary end-point was time to relapse (TTR).One hundred forty-five patients were treated with oregovomab (n = 73) or placebo (n = 72). For the population overall, median TTR was not different between treatments at 13.3 months for oregovomab and 10.3 months for placebo (P =.71). Immune responses were induced in most actively treated patients. This was associated with prolonged TTR. Quality of life was not adversely impacted by treatment. Adverse events were reported with similar frequency in oregovomab and placebo groups, indicating a benign safety profile. A long-term survival follow-up is ongoing. Cox analysis of relapse data identified significant factors: performance status, CA-125 before third cycle, and baseline CA-125. Further evaluation identified a subpopulation with favorable prognostic indicators designated as the successful front-line therapy (SFLT) population. For the SFLT population, TTR was 24.0 months in the oregovomab group compared with 10.8 months for placebo (unadjusted hazard ratio of 0.543 [95% CI, 0.287 to 1.025]), a hypothesis-generating observation.Consolidation therapy with oregovomab did not significantly improve TTR overall. A set of confirmatory phase III studies has been initiated to determine whether the SFLT population derives benefit from oregovomab treatment.
The joint impact on being overweight of self reported behaviours of eating quickly and eating until full : cross sectional survey
Authors: K. Maruyama, S. Sato, T. Ohira, K. Maeda, H. Noda, Y. Kubota, S. Nishimura, A. Kitamura, M. Kiyama, T. Okada, H. Imano, M. Nakamura, Y. Ishikawa, M. Kurokawa, S. Sasaki, H. Iso
Journal: BMJ (2008)

<b>Objective</b> To examine whether eating until full or eating quickly or combinations of these eating behaviours are associated with being overweight. <b>Design and participants</b> Cross sectional survey. <b>Setting</b> Two communities in Japan. <b>Participants</b> 3287 adults (1122 men, 2165 women) aged 30-69 who participated in surveys on cardiovascular risk from 2003 to 2006. <b>Main outcome measures</b> Body mass index (overweight ≥25.0) and the dietary habits of eating until full (lifestyle questionnaire) and speed of eating (validated brief self administered questionnaire). <b>Results</b> 571 (50.9%) men and 1265 (58.4%) women self reported eating until full, and 523 (45.6%) men and 785 (36.3%) women self reported eating quickly. For both sexes the highest age adjusted mean values for height, weight, body mass index, and total energy intake were in the eating until full and eating quickly group compared with the not eating until full and not eating quickly group. The multivariable adjusted odds ratio of being overweight for eating until full was 2.00 (95% confidence interval 1.53 to 2.62) for men and 1.92 (1.53 to 2.40) for women and for eating quickly was 1.84 (1.42 to 2.38) for men and 2.09 (1.69 to 2.59) for women. The multivariable odds ratio of being overweight with both eating behaviours compared with neither was 3.13 (2.20 to 4.45) for men and 3.21 (2.41 to 4.29) for women. <b>Conclusion</b> Eating until full and eating quickly are associated with being overweight in Japanese men and women, and these eating behaviours combined may have a substantial impact on being overweight.
Heartsink hotel revisited
Authors: R B. Cubey
Journal: BMJ (1993)

determine the level of services rather than to ration special services to particular patients, and it would be up to the government to decide the level of services offered to people.Smokers might argue that the revenue generated by their smoking sustains more than just the NHS budget.Secondly, failure rates derived by statistics do not apply to individual people.It is unethical to deny a patient the benefit of any treatment simply to reduce failure rates.Even the authors admit that the success rate of the operation is not spectacular.Probably there is a stronger case to look at the operation itself than at the imperfect people who have it.The third argument is that the damage caused by smoking is self inflicted.If we extend that argu- ment we might be tempted to deny services to people who do not adhere to a "healthy" lifestyle or strict medical advice; we would end up with an NHS treating only saints.
A Clinicopathologic Analysis of 177 Acral Melanomas in Koreans
Authors: Ho Joo Jung, Sun-Seog Kweon, Jee-Bum Lee, Seung-Chul Lee, Sook Jung Yun
Journal: JAMA Dermatology (2013)

The pathogenesis of acral melanoma remains unclear, even though trauma may be a predisposing factor. A study about the association of long-term physical stress with the incidence and spreading patterns through detailed anatomic mapping may be important to understand the unique features of acral melanoma.To analyze the epidemiologic and clinicopathologic characteristics of acral melanoma and evaluate how long-term physical stress or pressure strength influences acral melanoma based on the analysis of differences in incidence, prognosis of the distinct site (weight or non-weight-bearing portion of sole, volar, or subungual location), and the spreading pattern of melanoma on the soles.Cross-sectional, retrospective study of 177 Korean patients with acral melanoma from January 1, 1994, through October 31, 2012.Anatomic mapping and histopathologic examination of acral melanoma. RESULTS The male to female ratio was 1:1.03, and the mean age at first admission was 55.3 years. Acral lentiginous melanoma was the most common histopathologic subtype (85.9%), followed by nodular melanoma (12.8%). There was a high incidence of acral melanoma at more physically stressed sites, such as the center of the heels and inner forefoot. In addition, a peculiar spreading pattern with the long axis of melanoma, typically along naturally occurring creases due to long-term pressure on the soles, was often observed. The prognostic index and survival rate showed no significant difference between volar and subungual locations or between weight and non-weight-bearing portions of the soles.Clinicopathologic characteristics of acral melanoma diagnosed at an advanced stage and resulting in a low survival rate are not significantly different between Koreans and other Asians. Interestingly, based on our study, long-term physical stress or pressure strength can influence the incidence and spreading pattern of acral melanoma in a particular manner. Acral melanoma occurs on more physically stressed sites with the long axis along natural creases on the sole. A further prospective investigation, especially of in situ lesions, regarding location-based differences in incidence, progress, and survival is necessary to better understand the pathophysiologic characteristics of acral melanoma.
Reliability, validity and responsiveness to change of the Patient Report of Extent of Psoriasis Involvement (PREPI) for measuring body surface area affected by psoriasis
Authors: E.D. Dommasch, D.B. Shin, A.B. Troxel, D.J. Margolis, J.M. Gelfand
Journal: British Journal of Dermatology (2009)

The development of a simple, reliable, valid and responsive method for measuring the extent of skin involvement in psoriasis is important for use in epidemiological studies.We sought to investigate the psychometric characteristics of the Patient Report of Extent of Psoriasis Involvement (PREPI), a single-question method for measuring body surface area affected by psoriasis.This was a cross-sectional study of 140 patients with psoriasis, with an exploratory prospective longitudinal cohort component. Reliability was measured via a test-retest approach and criterion validity was investigated by comparing the PREPI with an assessment of body surface area of involvement by a dermatologist. We additionally compared Skindex-29 scores with the PREPI. To demonstrate responsiveness and establish a minimally important difference in the PREPI, we created receiver operating characteristic curves for the PREPI instrument.The test-retest reliability of the PREPI was nearly perfect [intraclass correlation coefficient (ICC) = 0.99, 95% confidence interval (CI) 0.97-0.99], and there was substantial agreement between patient and physician assessments (ICC = 0.82, 95% CI 0.75-0.87). The PREPI showed significant correlations with all Skindex-29 domains. We found the PREPI to be responsive to change and identified changes in the PREPI score that have good discrimination between patients with and without a minimally important clinical difference.Our study suggests that the PREPI is a reliable, valid and responsive measure of body surface area affected by psoriasis that may be useful for future epidemiological research.
Dysfunctional breathing in COPD
Authors: C K Connolly
Journal: Thorax (2003)

I was interested to read Dr Morgan’s review of dysfunctional breathing in asthma in the 2002 Year in Review,1 but the problem may be even greater in COPD.

Dr Morgan suggests that the problem may have serious consequences in terms of morbidity, but we have published indirect evidence of an association with mortality. In the 10 year follow up of the Darlington and Northallerton Asthma Study the odds ratio for the risk of dying in those who had …
Value of measuring diurnal peak flow variability in the recognition of asthma: a study in general practice
Authors: HA Thiadens, GH De Bock, FW Dekker, JA Huysman, JC Van Houwelingen, MP Springer, DS Postma
Journal: European Respiratory Journal (1998)

In this study we analysed the value of measuring diurnal peak flow variability (DPV) in general practice for diagnosing asthma or chronic obstructive pulmonary disease (COPD). One hundred and eighty-two subjects, aged 18-75 yrs, with undiagnosed asthma or COPD, presenting with a persistent cough recorded a peak flow diary twice daily for 2 weeks. A diagnosis of asthma or COPD was based on the recurrence of airway symptoms in the past year accompanied by spirometric measurements and a provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second. DPV was expressed as amplitude percentage highest of the day. Cut-off values of 15% and 20% (DPV15%, DPV20%) were employed and the number of days that these values were reached, was assessed. The influence of age, sex and pack-years smoking on DPV was analysed by logistic regression. The a priori probability to have asthma (n=69) or COPD (n=12) was 45% (81/182) and increased to &gt;70% with a DPV20% for at least 3, and a DPV15% for at least 4 days. Scoring formulas for asthma (DPV15% (number of days present) + 4 (if female sex)) and for asthma and COPD combined (8x DPV15% (number of days present) + 24 (if female sex) + pack-years smoking) predicted which subjects were at risk for having asthma (or COPD). Simple formulas based on the number of days with diurnal peak flow variability at 15%, female sex and pack-years can predict which patients with persistent cough are likely to have asthma or chronic obstructive pulmonary disease.
RETRACTED: Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial
Authors: Roberto Bolli, Atul R Chugh, Domenico D'Amario, John H Loughran, Marcus F Stoddard, Sohail Ikram, Garth M Beache, Stephen G Wagner, Annarosa Leri, Toru Hosoda, Fumihiro Sanada, Julius B Elmore, Polina Goichberg, Donato Cappetta, Naresh K Solankhi, Ibrahim Fahsah, D Gregg Rokosh, Mark S Slaughter, Jan Kajstura, Piero Anversa
Journal: The Lancet (2011)
Longitudinal Measurement of Clinical Mammographic Breast Density to Improve Estimation of Breast Cancer Risk
Authors: K. Kerlikowske, L. Ichikawa, D. L. Miglioretti, D. S. M. Buist, P. M. Vacek, R. Smith-Bindman, B. Yankaskas, P. A. Carney, R. Ballard-Barbash
Journal: JNCI Journal of the National Cancer Institute (2007)

BackgroundWhether a change over time in clinically measured mammographic breast density influences breast cancer risk is unknown.
Endothelin-1 Production during the Acute Chest Syndrome in Sickle Cell Disease
Authors: SAMUEL I. HAMMERMAN, STELLA KOUREMBANAS, TAMMY J. CONCA, MARISA TUCCI, MARK BRAUER, HARRISON W. FARBER
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

To investigate the role of the endothelial-derived vasoactive mediator endothelin (ET-1) in the acute chest syndrome (ACS), we incubated bovine pulmonary artery endothelial cells (BPAEC) with red blood cells (equivalent to a hematocrit of 20%) and/or autologous plasma (1:10 dilution) from two patients during ACS and during routine clinic visits. Cellular RNA was analyzed for ET-1 transcripts by Northern analysis and ET-1 protein levels in BPAEC supernatants and in plasma measured by radioimmunoassay. ET-1 mRNA expression and protein levels increased in BPAEC exposed to plasma obtained during ACS; in contrast, exposure to plasma obtained during routine clinic visits did not alter BPAEC ET-1 mRNA expression or protein levels. Plasma ET-1 level was elevated during ACS, decreased during resolution, and remained slightly elevated during routine clinic visits. Plasma obtained from one patient 4 d prior to hospitalization for vasoocclusive crisis contained the highest ET-1 level and markedly increased BPAEC ET-1 mRNA expression and protein levels. In both patients, BPAEC ET-1 mRNA and protein expression in vitro and plasma ET-1 levels in vivo correlated with stage of disease and occurred in the absence of direct erythrocyte contact in vitro. These observations suggest that ET-1 production contributes to development of ACS.
Sputum and plasma endothelin-1 levels in exacerbations of chronic obstructive pulmonary disease
Authors: M Roland
Journal: Thorax (2001)

<h3>BACKGROUND</h3> Endothelin (ET)-l is a bronchoconstrictor peptide produced in the airways. It has been implicated in the pathogenesis of asthma and virally mediated airway inflammation and may play a role in exacerbations of chronic obstructive pulmonary disease (COPD). <h3>METHODS</h3> Seventy one patients with COPD were followed prospectively and sampled for plasma and sputum ET-1 levels when stable and during an exacerbation. Sputum was also examined for cytokines, human rhinovirus, and <i>Chlamydia pneumoniae</i>. <h3>RESULTS</h3> Plasma ET-1 levels were available for 67 patients with stable COPD (mean (SD) 0.58 (0.31) pg/ml); 28 pairs of stable-exacerbation plasma samples had a mean stable ET-1 level of 0.54 (0.30) pg/ml rising to 0.67 (0.35) pg/ml at exacerbation (mean difference 0.13, 95% confidence interval (CI) 0.04 to 0.21, p = 0.004). Plasma ET-1 levels in the 67 patients with stable COPD were inversely correlated with baseline forced expiratory volume in one second (FEV<sub>1</sub>;<i>r</i> = –0.29, p = 0.022) and forced vital capacity (FVC; <i>r</i> = –0.38, p = 0.002). The change in plasma ET-1 levels during an exacerbation correlated with the change in oxygen saturation (Sao<sub>2</sub>;<i>r</i> = –0.41, p = 0.036). In 14 stable-exacerbation pairs of sputum samples median stable ET-1 levels were 5.37 (0.97–21.95) pg/ml rising to 34.68 (13.77–51.95) pg/ml during an exacerbation (mean difference 25.14, 95% CI 3.77 to 46.51, p = 0.028). This increase in sputum ET-1 levels correlated with the increase in plasma ET-1 levels (<i>r</i> = 0.917, p = 0.001) and sputum interleukin (IL)-6 levels (<i>r</i> = 0.718, p = 0.013). <h3>CONCLUSIONS</h3> Sputum levels of ET-1 rise in COPD patients during an exacerbation and this is reflected by a smaller rise in plasma ET-1 levels. ET-1 may have a role in mediating airway inflammatory changes during exacerbations of COPD.
The Medical World of Benjamin Franklin
Authors: L. Gensel
Journal: Journal of the Royal Society of Medicine (2005)

In a 1747 letter to his parents, Benjamin Franklin noted 'I apprehend I am to busy in prescribing, and meddling in the Dr's sphere, when any of you complain of ails in your letters: but as I always employ a physician myself when any disorder arises in my family and submit implicitly to his orders in every thing, so I hope you consider my advice, when I give any, only as a mark of my good will, and put no more of it in practice that happens to agree with what your Dr. directs.' 1 After giving this assurance that he did not mean to play the physician, Franklin continued with advice about remedies for bladder stone and gravel.In fact, throughout his life he dispensed such advice and wrote knowledgeably on a number of health-related issues.
The CpG Island Methylator Phenotype: What's in a Name?
Authors: Laura A.E. Hughes, Veerle Melotte, Joachim de Schrijver, Michiel de Maat, Vincent T.H.B.M. Smit, Judith V.M.G. Bovée, Pim J. French, Piet A. van den Brandt, Leo J. Schouten, Tim de Meyer, Wim van Criekinge, Nita Ahuja, James G. Herman, Matty P. Weijenberg, Manon van Engeland
Journal: Cancer Research (2013)

Abstract Although the CpG island methylator phenotype (CIMP) was first identified and has been most extensively studied in colorectal cancer, the term “CIMP” has been repeatedly used over the past decade to describe CpG island promoter methylation in other tumor types, including bladder, breast, endometrial, gastric, glioblastoma (gliomas), hepatocellular, lung, ovarian, pancreatic, renal cell, and prostate cancers, as well as for leukemia, melanoma, duodenal adenocarninomas, adrenocortical carcinomas, and neuroblastomas. CIMP has been reported to be useful for predicting prognosis and response to treatment in a variety of tumor types, but it remains unclear whether or not CIMP is a universal phenomenon across human neoplasia or if there should be cancer-specific definitions of the phenotype. Recently, it was shown that somatic isocitrate dehydrogenase-1 (IDH1) mutations, frequently observed in gliomas, establish CIMP in primary human astrocytes by remodeling the methylome. Interestingly, somatic IDH1 and IDH2 mutations, and loss-of-function mutations in ten-eleven translocation (TET) methylcytosine dioxygenase-2 (TET2) associated with a hypermethylation phenotype, are also found in multiple enchondromas of patients with Ollier disease and Mafucci syndrome, and leukemia, respectively. These data provide the first clues for the elucidation of a molecular basis for CIMP. Although CIMP appears as a phenomenon that occurs in various cancer types, the definition is poorly defined and differs for each tumor. The current perspective discusses the use of the term CIMP in cancer, its significance in clinical practice, and future directions that may aid in identifying the true cause and definition of CIMP in different forms of human neoplasia. Cancer Res; 73(19); 5858–68. ©2013 AACR.
How early should ankylosing spondylitis be treated with tumour necrosis factor blockers?
Authors: J Sieper
Journal: Annals of the Rheumatic Diseases (2005)

Recognition and treatment of ankylosing spondylitis (AS) in the early stages of the disease has yet to be established. This paper considers the evidence available and the questions that need to be answered regarding the benefits of early diagnosis and treatment with tumour necrosis factor (TNF) blockers in AS. The authors conclude that AS can and has to be diagnosed earlier than is being done at present, before radiological changes are evident, and the potential of TNF blockers to induce long term remission if given early enough needs to be clarified.