tbuckley/cabot-search huggingface dataset:
The Wells Rule Does Not Adequately Rule Out Deep Venous Thrombosis in Primary Care Patients
Authors: Ruud Oudega, Arno W. Hoes, Karel G.M. Moons
Journal: Annals of Internal Medicine (2005)

Using data from secondary care outpatients, Wells and colleagues developed a diagnostic rule to estimate the probability of the presence of deep venous thrombosis (DVT). The accuracy of the Wells rule has not been properly validated for use in primary care patients in whom DVT is suspected.To validate the diagnostic accuracy of the Wells rule, with and without D-dimer testing, in a primary care setting.Cross-sectional study with prospective data collection from 1 January 2002 to 1 March 2003.110 primary care practices in a circumscribed geographic region in The Netherlands.1295 consecutive patients who consulted their primary care physician about symptoms suggestive of DVT.All patients underwent history-taking and physical examination to calculate the Wells rule score, and D-dimer testing. Repeated leg ultrasonography was the reference standard to determine the true presence or absence of DVT.In the primary care setting, 12.0% of patients in the low-risk group had DVT; the original study by Wells and colleagues reported a rate of 3% among such patients. When combined with negative results on a D-dimer test, the Wells rule yielded a prevalence of DVT of 2.9% in the lowest-risk group, whereas the prevalence was 0.9% in the original study.Patients with previous DVT were included, and the diagnostic reference standard was different from that used in Wells and colleagues' original study.The Wells rule, alone or in combination with D-dimer testing, does not guarantee accurate estimation of risk in primary care patients in whom DVT is suspected.
Newly expressed SUR1-regulated NCCa-ATP channel mediates cerebral edema after ischemic stroke
Authors: J Marc Simard, Mingkui Chen, Kirill V Tarasov, Sergei Bhatta, Svetlana Ivanova, Ludmila Melnitchenko, Natalya Tsymbalyuk, G Alexander West, Volodymyr Gerzanich
Journal: Nature Medicine (2006)
Effect of High Dose Inhaled Steroid on Cells, Cytokines, and Proteases in Induced Sputum in Chronic Obstructive Pulmonary Disease
Authors: SARAH V. CULPITT, WASIM MAZIAK, STELIOS LOUKIDIS, JULIA A. NIGHTINGALE, JOHN L. MATTHEWS, PETER J. BARNES
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Inhaled corticosteroids are widely prescribed for the treatment of stable chronic obstructive pulmonary disease (COPD), despite lack of proven efficacy. Because COPD involves airway inflammation and probable protease-antiprotease imbalance, we examined the effect of high dose fluticasone propionate on markers of activity of both pathogenetic mechanisms. Thirteen patients with COPD were treated with fluticasone propionate (500 μ g twice a day) for 4 wk, delivered via MDI and spacer, in a double-blind crossover study. There was no clinical benefit in terms of lung function or symptom scores, and induced sputum inflammatory cells, percentage neutrophils, and IL-8 levels were unchanged. Sputum supernatant elastase activity, matrix metalloproteinase (MMP)-1, MMP-9, and the antiproteases secretory leukoprotease inhibitor (SLPI) and tissue inhibitor of metalloproteinase (TIMP)-1 were similarly unaffected by treatment. These results add to previous evidence that inhaled steroids have no anti-inflammatory action in stable COPD. Furthermore, inhaled steroids do not appear to redress the protease-antiprotease imbalance that is thought to be important in the pathogenesis of airway obstruction. Culpitt SV, Maziak W, Loukidis S, Nightingale JA, Matthews JL, Barnes PJ. Effect of high dose inhaled steroid on cells, cytokines, and proteases in induced sputum in chronic obstructive pulmonary disease.
Are activity indices helpful in assessing active intestinal inflammation in Crohn's disease?
Authors: G Crama-Bohbouth, A S Pena, I Biemond, H W Verspaget, D Blok, J W Arndt, I T Weterman, E K Pauwels, C B Lamers
Journal: Gut (1989)

We have investigated the correlation of 24 h and 48 h faecal Indium-111 excretion with each other and with several clinical activity indices for Crohn9s disease (CD): Crohn9s disease activity index (CDAI), activity index (AI), simple index (SI), Oxford score, and laboratory parameters, such as ESR, serum albumin, orosomucoid, C-reactive protein, alpha-l-antitrypsin (alpha 1-AT) faecal concentration, and alpha 1-AT clearance in 58 CD patients (37 with small bowel and 21 with colonic disease). A significant correlation was found between 24 and 48 h faecal Indium-111 excretion for small bowel (r = 0.708, p less than 0.0001) and colonic disease (r = 0.994, p less than 0.0001). The median faecal Indium-111 excretion for colonic involvement (4%; 0.15-50% median and range) was significantly (p less than 0.005) higher than that for small bowel disease (0.45%; 0.03-2.9%). No significant correlation was found between faecal Indium-111 excretion and any activity index in the patients with small bowel disease, while in the group of patients with colonic localisation only the AI showed a significant correlation (r = 0.593, p less than 0.02). Faecal Indium-111 excretion was significantly correlated with alpha 1-AT clearance (r = 0.712, p less than 0.0001) and faecal alpha 1-AT concentration (r = 0.750, p less than 0.0001) in small bowel and in colonic localisation (r = 0.530, p less than 0.02 and r = 0.444, p less than 0.05). Serum albumin was significantly correlated only in the group of patients with colonic disease (r = -0.593, p less than 0.05). The present study shows poor agreement between activity indices, serum parameters of activity and faecal Indium-111 excretion. As a good correlation was found with the alpha1-clearance, which reflects losses into the gut, these results may suggest that faecal Indium excretion does not only reflect activity of inflammation, but my relate to the extent of intestinal ulceration.
Circulating U2 small nuclear RNA fragments as a novel diagnostic biomarker for primary central nervous system lymphoma
Authors: Alexander Baraniskin, Elena Zaslavska, Stefanie Nöpel-Dünnebacke, Guido Ahle, Sabine Seidel, Uwe Schlegel, Wolff Schmiegel, Stephan Hahn, Roland Schroers
Journal: Neuro-Oncology (2015)

Primary central nervous system lymphomas (PCNSLs) are highly aggressive tumors. Chemotherapy has improved prognosis significantly; however, early diagnosis is crucial for effective treatment. Presently, the diagnosis of PCNSL depends on histopathology of tumor biopsies. We have previously demonstrated differential expression of microRNAs in cerebrospinal fluid (CSF) samples from patients with PCNSL. Based on promising findings about circulating U2 small nuclear RNA fragments (RNU2-1f) as novel blood-based biomarkers for pancreatic, colorectal, and lung cancer, we investigated RNU2-1f in the CSF of PCNSL patients. CSF was collected from patients with PCNSL (n = 72) and control patients with various neurologic disorders (n = 47). Sequential CSF samples were collected from 9 PCNSL patients. RNU2-1f levels were measured by real-time polymerase chain reaction. Measurement of RNU2-1f levels in CSF enabled the differentiation of patients with PCNSL from controls with an area under the curve (AUC) of 0.909 with a sensitivity of 68.1% and a specificity of 91.4%. The diagnostic accuracy was further improved by combined determination of RNU2-1f and miR-21, resulting in AUC of 0.987 with a sensitivity of 91.7% and a specificity of 95.7%. In consecutive measurements of RNU2-1f, which were performed in 9 patients at different stages of the disease course, RNU2-1f CSF levels paralleled the course of the disease. Our data suggest that the measurement of RNU2-1f detected in CSF can be used as a diagnostic marker and also as a possible marker for treatment monitoring. These promising results need to be evaluated within a larger patient cohort.
Prospective Study of Peripregnancy Consumption of Peanuts or Tree Nuts by Mothers and the Risk of Peanut or Tree Nut Allergy in Their Offspring
Authors: A. Lindsay Frazier, Carlos A. Camargo, Susan Malspeis, Walter C. Willett, Michael C. Young
Journal: JAMA Pediatrics (2013)

The etiology of the increasing childhood prevalence of peanut or tree nut (P/TN) allergy is unknown.To examine the association between peripregnancy consumption of P/TN by mothers and the risk of P/TN allergy in their offspring.Prospective cohort study. The 10,907 participants in the Growing Up Today Study 2, born between January 1, 1990, and December 31, 1994, are the offspring of women who previously reported their diet during, or shortly before or after, their pregnancy with this child as part of the ongoing Nurses' Health Study II. In 2006, the offspring reported physician-diagnosed food allergy. Mothers were asked to confirm the diagnosis and to provide available medical records and allergy test results. Two board-certified pediatricians, including a board-certified allergist/immunologist, independently reviewed each potential case and assigned a confirmation code (eg, likely food allergy) to each case. Unadjusted and multivariable logistic regression analyses were used to evaluate associations between peripregnancy consumption of P/TN by mothers and incident P/TN allergy in their offspring.Peripregnancy consumption of P/TN.Physician-diagnosed P/TN allergy in offspring.Among 8205 children, we identified 308 cases of food allergy (any food), including 140 cases of P/TN allergy. The incidence of P/TN allergy in the offspring was significantly lower among children of the 8059 nonallergic mothers who consumed more P/TN in their peripregnancy diet (≥ 5 times vs <1 time per month: odds ratio = 0.31; 95% CI, 0.13-0.75; P(trend) = .004). By contrast, a nonsignificant positive association was observed between maternal peripregnancy P/TN consumption and risk of P/TN allergy in the offspring of 146 P/TN-allergic mothers (P(trend) = .12). The interaction between maternal peripregnancy P/TN consumption and maternal P/TN allergy status was statistically significant (P(interaction) = .004).Among mothers without P/TN allergy, higher peripregnancy consumption of P/TN was associated with lower risk of P/TN allergy in their offspring. Our study supports the hypothesis that early allergen exposure increases tolerance and lowers risk of childhood food allergy.
Influence of Lead Selection and Population on Automated Measurement of QT Dispersion
Authors: P. W. Macfarlane, Stephanie C. McLaughlin, J. Christine Rodger
Journal: Circulation (1998)

The study of QT dispersion (QTd) is of increasing clinical interest, but there are very few data in large healthy populations. Furthermore, there is still discussion on the extent to which QTd reflects dispersion of measurement. This study addresses these problems.Twelve-lead ECGs recorded on 1501 apparently healthy adults and 1784 healthy neonates, infants, and children were used to derive normal limits of QTd and QT intervals by use of a fully automated approach. No age gradient or sex differences in QTd were seen and it was found that an upper limit of 50 ms was highly specific. Three-orthogonal-lead ECGs (n=1220) from the Common Standards for Quantitative Electrocardiography database were used to generate derived 12-lead ECGs, which had a significant increase in QTd of 10.1+/-13.1 ms compared with the original orthogonal-lead ECG but a mean difference of only 1.63+/-12.2 ms compared with the original 12-lead ECGs. In a population of 361 patients with old myocardial infarction, there was a statistically significant increase in mean QTd compared with that of the adult normal group (32.7+/-10.0 versus 24.53+/-8.2 ms; P<0. 0001). An estimate of computer measurement error was also obtained by creating 2 sets of 1220 ECGs from the original set of 1220. The mean error (difference in QTd on a paired basis) was found to be 0. 28+/-9.7 ms.These data indicate that QTd is age and sex independent, has a highly specific upper normal limit of 50 ms, is significantly lower in the 3-orthogonal-lead than in the 12-lead ECG, and is longer in patients with a previous myocardial infarction than in normal subjects.
DNA Methylation Predicts Survival and Response to Therapy in Patients With Myelodysplastic Syndromes
Authors: Lanlan Shen, Hagop Kantarjian, Yi Guo, E Lin, Jianqin Shan, Xuelin Huang, Donald Berry, Saira Ahmed, Wei Zhu, Sherry Pierce, Yutaka Kondo, Yasuhiro Oki, Jaroslav Jelinek, Hussain Saba, Eli Estey, Jean-Pierre J. Issa
Journal: Journal of Clinical Oncology (2009)

Purpose The current classification systems of myelodysplastic syndromes (MDS), including the International Prognostic Scoring System (IPSS), do not fully reflect the molecular heterogeneity of the disease. Molecular characterization may predict clinical outcome and help stratify patients for targeted therapies. Epigenetic therapy using decitabine, a DNA hypomethylating agent, is clinically effective for the treatment of MDS. Therefore, we investigated the association between DNA methylation and clinical outcome in MDS. Patients and Methods We screened 24 patients with MDS for promoter CpG island methylation of 24 genes and identified aberrant hypermethylation at 10 genes. We then performed quantitative methylation analyses by bisulfite pyrosequencing of the identified genes in 317 patient samples from three independent studies and assessed relations between methylation and clinical outcome. Results In an initial training cohort of 89 patients with MDS, methylation frequencies of individual genes ranged from 7% to 70% and were highly concordant. Therefore, we defined a methylation z score based on all genes for each patient. We found that patients with higher levels of methylation, compared with patients with lower levels, had a shorter median overall survival (12.3 v 17.5 months, respectively; P = .04) and shorter median progression-free survival (6.4 v 14.9 months, respectively; P = .009). This methylation prognostic model was independent of age, sex, and IPSS group. Applied to two validation cohorts (228 patients), this model was confirmed as an independent prognostic predictor for survival. Although methylation at baseline did not correlate with clinical response to decitabine, we observed a significant correlation between reduced methylation over time and clinical responses. Conclusion DNA methylation predicts overall and progression-free survival in MDS.
Increased L1 Retrotransposition in the Neuronal Genome in Schizophrenia
Authors: Miki Bundo, Manabu Toyoshima, Yohei Okada, Wado Akamatsu, Junko Ueda, Taeko Nemoto-Miyauchi, Fumiko Sunaga, Michihiro Toritsuka, Daisuke Ikawa, Akiyoshi Kakita, Motoichiro Kato, Kiyoto Kasai, Toshifumi Kishimoto, Hiroyuki Nawa, Hideyuki Okano, Takeo Yoshikawa, Tadafumi Kato, Kazuya Iwamoto
Journal: Neuron (2014)
Next Steps for Breast Implant–Associated Anaplastic Large-Cell Lymphoma
Authors: Anna E. Mazzucco
Journal: Journal of Clinical Oncology (2014)

TO THEEDITOR: The excellent analysis by Miranda et al 1 based on extended follow-up of patients with breast implant–associated anaplastic large-cell lymphoma (ALCL) adds to the mounting evidence of the potential for aggressive clinical behavior of this disease. 2,3 For the first time, these researchers identified two patient subpopulations with distinct clinical outcomes: 75% of the patients with solid ALCL tumors had survived at 5 years postdiagnosis, compared with 100% of patients with effusion-type ALCL. In contrast, earlier studies suggested that breast implant–associated ALCL was likely to be clinically indolent and more similar to primary cutaneous, anaplastic lymphoma kinase (ALK) –negative ALCL, rather than the more aggressive systemic form of the disease. 4,5
Applying for ethical approval for research in the United Kingdom
Authors: A Smajdor, M R Sydes, L Gelling, M Wilkinson
Journal: BMJ (2009)

This article offers practical advice on how to expedite the ethical review process. Applying for ethical review in the United Kingdom can be time consuming and burdensome for researchers.1 2 3 The process can often be made easier by implementing relatively minor changes in the early stages of drawing up the application. In this article we discuss the practicalities of preparing an application for ethical review, and the process by which decisions are made. We offer advice on how to avoid common problems when applying to a research ethics committee and provide information on the integrated research application system, launched in January 2008. #### Glossary of useful terms
Signal Transduction Mechanisms Mediating the Physiological and Pathophysiological Actions of Angiotensin II in Vascular Smooth Muscle Cells
Authors: Rhian M. Touyz, Ernesto L. Schiffrin
Journal: Pharmacological Reviews (2000)

Until recently, the signaling events elicited in vascular smooth muscle cells by angiotensin II (Ang II) were considered to be rapid, short-lived, and divided into separate linear pathways, where intracellular targets of the phospholipase C-diacylglycerol-Ca(2+) axis were distinct from those of the tyrosine kinase- and mitogen-activated protein kinase- dependent pathways. However, these major intracellular signaling cascades do not function independently and are actively engaged in cross-talk. Downstream signals from the Ang II-bound receptors converge to elicit complex and multiple responses. The exact adapter proteins or "go-between" molecules that link the multiple intracellular pathways await clarification. Ang II induces a multitude of actions in various tissues, and the signaling events following occupancy and activation of angiotensin receptors are tightly controlled and extremely complex. Alterations of these highly regulated signaling pathways in vascular smooth cells may be pivotal in structural and functional abnormalities that underlie vascular pathological processes in cardiovascular diseases such as hypertension, atherosclerosis, and post-interventional restenosis.
Genetics and Cytogenetics of Multiple Myeloma
Authors: Rafael Fonseca, Bart Barlogie, Regis Bataille, Christian Bastard, P. Leif Bergsagel, Marta Chesi, Faith E. Davies, Johannes Drach, Philip R. Greipp, Ilan R. Kirsch, W. Michael Kuehl, Jesus M. Hernandez, Stephane Minvielle, Linda M. Pilarski, John D. Shaughnessy, A. Keith Stewart, Herve Avet-Loiseau
Journal: Cancer Research (2004)

Abstract Much has been learned regarding the biology and clinical implications of genetic abnormalities in multiple myeloma. Because of recent advances in the field, an International Workshop was held in Paris in February of 2003. This summary describes the consensus recommendations arising from that meeting with special emphasis on novel genetic observations. For instance, it is increasingly clear that translocations involving the immunoglobulin heavy-chain locus are important for the pathogenesis of one-half of patients. As a corollary, it also clear that the remaining patients, lacking IgH translocations, have hyperdiploidy as the hallmark of their disease. Several important genetic markers are associated with a shortened survival such as chromosome 13 monosomy, hypodiploidy, and others. The events leading the transformation of the monoclonal gammopathy of undetermined significance (MGUS) to myeloma are still unclear. One of the few differential genetic lesions between myeloma and MGUS is the presence of ras mutations in the latter. Gene expression platforms are capable of detecting many of the genetic aberrations found in the clonal cells of myeloma. Areas in need of further study were identified. The study of the genetic aberrations will likely form the platform for targeted therapy for the disease.
The Olympics and the National Health Service: a definition of health
Authors: Kamran Abbasi
Journal: Journal of the Royal Society of Medicine (2012)

When a 16-year old Chinese girl, Ye Shiwen, swims at a speed that even the world's best male swimmers struggle to match, and Usain Bolt and his fellow sprinters run like the wind, our minds turn to the limits of human endeavour.1 Health, as the Olympic Games have reminded us, is the purpose of medicine. The World Health Organization's age-old mantra of ‘Health for All’ often seems an abstract slogan since health is a concept we struggle harder to define than disease. Perhaps the definition of health is being in the peak of physical condition that allows an athlete to win an Olympic gold medal? Perhaps it is nothing more than happiness, despite our physical state?

If the Olympic Games conjure images of finely honed athletes in our minds, the 2012 Olympic Games will be remembered by health professionals for the way the opening ceremony celebrated the National Health Service (NHS). Dancing doctors and nurses, Great Ormond Street Hospital, a pulse beat that circled the Olympic Stadium, were prominent features of a ‘Best of British’ sequence masterminded by film director Danny Boyle.

This was too political a statement for some. A visceral and ideological struggle for the soul of the NHS in 2012 cannot have escaped Boyle, an astute social commentator. Did celebrating the place of the NHS in the nation's psyche support the arguments and the campaign of this year's antireformists? Possibly, but Boyle also reminded of us that along with James Bond, Mr Bean, William Shakespeare, cricket, David Beckham, the Queen and heroic failure, the NHS is a peculiarly British institution. In a planet dominated by insurance-based health systems, the NHS remains an experiment that fascinates the world and provokes fierce and passionate debate within these shores.

But the Olympic Games also reminded us that flaws and failure are much more common than success. Perfection is a dream that is rarely achieved. Are humans ever more perfect than the moment of birth? Only one person or team wins a gold medal in any event. Our lives and bodies are flawed. Our organs, dreams and aspirations fail. The NHS is no different. Flaws and failures are ever present; perfection is a dream impossible to achieve. Yet the NHS strives, in its way, for ‘Health for All’ – and that human endeavour might be more fulfilling once health itself is satisfactorily defined.
Active Antiviral T-Lymphocyte Response Can Be Redirected against Tumor Cells by Antitumor Antibody × MHC/Viral Peptide Conjugates
Authors: Valérie Cesson, Kathrin Stirnemann, Bruno Robert, Immanuel Luescher, Thomas Filleron, Giampietro Corradin, Jean-Pierre Mach, Alena Donda
Journal: Clinical Cancer Research (2006)

Abstract Purpose: To redirect an ongoing antiviral T-cell response against tumor cells in vivo, we evaluated conjugates consisting of antitumor antibody fragments coupled to class I MHC molecules loaded with immunodominant viral peptides. Experimental Design: First, lymphochoriomeningitis virus (LCMV)–infected C57BL/6 mice were s.c. grafted on the right flank with carcinoembryonic antigen (CEA)–transfected MC38 colon carcinoma cells precoated with anti-CEA × H-2Db/GP33 LCMV peptide conjugate and on the left flank with the same cells precoated with control anti-CEA F(ab′)2 fragments. Second, influenza virus–infected mice were injected i.v., to induce lung metastases, with HER2-transfected B16F10 cells, coated with either anti-HER2 × H-2Db/NP366 influenza peptide conjugates, or anti-HER2 F(ab′)2 fragments alone, or intact anti-HER2 monoclonal antibody. Third, systemic injections of anti-CEA × H-2Db conjugates with covalently cross-linked GP33 peptides were tested for the growth inhibition of MC38-CEA+ cells, s.c. grafted in LCMV-infected mice. Results: In the LCMV-infected mice, five of the six grafts with conjugate-precoated MC38-CEA+ cells did not develop into tumors, whereas all grafts with F(ab′)2-precoated MC38-CEA+ cells did so (P = 0.0022). In influenza virus–infected mice, the group injected with cells precoated with specific conjugate had seven times less lung metastases than control groups (P = 0.0022 and P = 0.013). Most importantly, systemic injection in LCMV-infected mice of anti-CEA × H-2Db/cross-linked GP33 conjugates completely abolished tumor growth in four of five mice, whereas the same tumor grew in all five control mice (P = 0.016). Conclusion: The results show that a physiologic T-cell antiviral response in immunocompetent mice can be redirected against tumor cells by the use of antitumor antibody × MHC/viral peptide conjugates.