tbuckley/cabot-search huggingface dataset:
Sex differences in pain
Authors: K J Berkley
Journal: Behavioral and Brain Sciences (1997)

Are there sex differences in pain? For experimentally delivered somatic stimuli, females have lower thresholds, greater ability to discriminate, higher pain ratings, and less tolerance of noxious stimuli than males. These differences, however, are small, exist only for certain forms of stimulation and are affected by many situational variables such as presence of disease, experimental setting, and even nutritive status. For endogenous pains, women report more multiple pains in more body regions than men. With no obvious underlying rationale, some painful diseases are more prevalent among females, others among males and, for many diseases, symptoms differ between females and males. Sex differences in attitudes exist that affect not only reporting, coping, and responses to treatment, but also measurement and treatment. So many variables are operative, however, that the most striking feature of sex differences in reported pain experience is the apparent overall lack of them. On the other hand, deduction from known biological sex differences suggests that these are powerful sex differences in the operation of pain mechanisms. First, the vaginal canal provides an additional route in women for internal trauma and invasion by pathological agents that puts them at greater risk for developing hyperalgesia in multiple body regions. Second, sex differences in temporal patterns are likely to give rise to sex differences in how pain is “learned” and stimuli are interpreted, a situation that could lead to a greater variability and wider range of pains without obvious peripheral pathology among females. Third, sex differences in the actions of sex hormones suggest pain-relevant differences in the operation of many neuroactive agents, opiate and nonopiate systems, nerve growth factor, and the sympathetic system. Thus, while inductive analysis of existing data demonstrate more similarities than differences in pain experience between females and males, deductive analysis suggests important operational sex differences in its production.
Reproducibility of 6-minute walking test in patients with COPD
Authors: N.A. Hernandes, E.F.M. Wouters, K. Meijer, J. Annegarn, F. Pitta, M.A. Spruit
Journal: European Respiratory Journal (2010)

The reproducibility of the 6-min walking test (6MWT) needs to be more solidly studied. This study aimed to investigate the reproducibility of two 6MWTs performed on subsequent days in a large and representative sample of patients with chronic obstructive pulmonary disease (COPD), and to quantify the learning effect between the two tests, as well as its determinants. In a retrospective observational study, 1,514 patients with COPD performed two 6MWTs on subsequent days. Other measurements included body composition (dual X-ray absorptiometry), dyspnoea (Medical Research Council scale) and comorbidity (Charlson index). Although the 6MWT was reproducible (intraclass correlation coefficient = 0.93), patients walked farther in the second test (391 m, 95% CI 155–585 m versus 418 m, 95% CI 185–605 m; p&lt;0.0001). On average, the second 6MWT increased by 27 m (or 7%), and 82% of patients improved in the second test. Determinants of improvement ≥42 m in the second test (upper limit of the clinically important change) were as follows: first 6MWT &lt;350 m, Charlson index &lt;2 and body mass index &lt;30 kg·m −2 (OR 2.49, 0.76 and 0.60, respectively). The 6MWT was statistically reproducible in a representative sample of patients with COPD. However, the vast majority of patients improved significantly in the second test by an average learning effect of 27 m.
A framework for variation discovery and genotyping using next-generation DNA sequencing data
Authors: Mark A DePristo, Eric Banks, Ryan Poplin, Kiran V Garimella, Jared R Maguire, Christopher Hartl, Anthony A Philippakis, Guillermo del Angel, Manuel A Rivas, Matt Hanna, Aaron McKenna, Tim J Fennell, Andrew M Kernytsky, Andrey Y Sivachenko, Kristian Cibulskis, Stacey B Gabriel, David Altshuler, Mark J Daly
Journal: Nature Genetics (2011)
Overdiagnosis in Cancer
Authors: H Gilbert Welch, William C Black
Journal: JNCI Journal of the National Cancer Institute (2010)

This article summarizes the phenomenon of cancer overdiagnosis-the diagnosis of a "cancer" that would otherwise not go on to cause symptoms or death. We describe the two prerequisites for cancer overdiagnosis to occur: the existence of a silent disease reservoir and activities leading to its detection (particularly cancer screening). We estimated the magnitude of overdiagnosis from randomized trials: about 25% of mammographically detected breast cancers, 50% of chest x-ray and/or sputum-detected lung cancers, and 60% of prostate-specific antigen-detected prostate cancers. We also review data from observational studies and population-based cancer statistics suggesting overdiagnosis in computed tomography-detected lung cancer, neuroblastoma, thyroid cancer, melanoma, and kidney cancer. To address the problem, patients must be adequately informed of the nature and the magnitude of the trade-off involved with early cancer detection. Equally important, researchers need to work to develop better estimates of the magnitude of overdiagnosis and develop clinical strategies to help minimize it.
A Novel Submicron Formulation of Nebulized Budesonide Delivered by a Vibrating Mesh Nebulizer Significantly Improves Delivery Efficiency at One-Fifth of the Nominal Dose of both Pulmicort Respules® and a Generic Budesonide Suspensions Delivered via a Jet Nebulizer - A Potentially Important Advancement in Pediatric Asthma
Authors: A. Bosco, M. Castillo, M. Conde, M. Luangvala
Journal: Journal of Allergy and Clinical Immunology (2010)
Estimating the Distribution of Selection Coefficients from Phylogenetic Data with Applications to Mitochondrial and Viral DNA
Authors: Rasmus Nielsen, Ziheng Yang
Journal: Molecular Biology and Evolution (2003)

The distribution of selection coefficients of new mutations is of key interest in population genetics. In this paper we explore how codon-based likelihood models can be used to estimate the distribution of selection coefficients of new amino acid replacement mutations from phylogenetic data. To obtain such estimates we assume that all mutations at the same site have the same selection coefficient. We first estimate the distribution of selection coefficients from two large viral data sets under the assumption that the viral population size is the same along all lineages of the phylogeny and that the selection coefficients vary among sites. We then implement several new models in which the lineages of the phylogeny may have different population sizes. We apply the new models to a data set consisting of the coding regions from eight primate mitochondrial genomes. The results suggest that there might be little power to determine the exact shape of the distribution of selection coefficient but that the normal and gamma distributions fit the data significantly better than the exponential distribution.
Rapid diagnosis of sputum negative miliary tuberculosis using the flexible fibreoptic bronchoscope.
Authors: P A Willcox, P D Potgieter, E D Bateman, S R Benatar
Journal: Thorax (1986)

Acid fast bacilli are seldom identified by direct staining of sputum smears in patients with miliary tuberculosis, so that delays in diagnosis are common. We report 41 patients with miliary tuberculosis who had negative sputum smears and who underwent bronchoscopy, bronchial brushing, and transbronchial biopsy. In two patients the procedure was repeated. A definitive diagnosis was obtained from bronchoscopy in 34 patients (83%). Bronchial brushings yielded Mycobacterium tuberculosis in 24 of 42 bronchoscopies (57%), 13 from direct smear and a further 11 from culture only. Transbronchial biopsies were diagnostic in 30 of 41 procedures (73%), 28 from histological appearances, one from direct smear of the biopsy specimen, and another exclusively from culture. A rapid diagnosis was established in most patients (27/34), either by direct smear of brushings or biopsy specimens only (5), by histological examination only (14), or by both direct smear of brushings and biopsy specimens only (5), by histological examination only (14), or by both direct smear of brushings and histological examination (8). The diagnosis was confirmed later in a further seven patients by culture of brushings or specimens; in five of these non-caseating granulomas were initially found by histological examination. Fibreoptic bronchoscopy is a valuable technique for rapidly establishing the diagnosis of miliary tuberculosis.
Vagal Nerve Stimulation in Chronic Heart Failure: An Antiinflammatory Intervention?
Authors: Jochen Springer, Darlington O. Okonko, Stefan D. Anker
Journal: Circulation (2004)

To the Editor:Li et al 1 recently reported that vagal nerve stimulation improved survival in otherwise untreated rats with heart failure secondary to left coronary artery ligation.Although this finding is indeed intriguing and of potential therapeutic importance, the authors are understandably speculative about the possible mechanisms underlying this observation.The authors discuss that the beneficial effects seen in their study cannot solely be ascribed to vagal inhibition of myocardial presynaptic norepinephrine release or to the attenuation of cardiomyocyte G-protein interactions that normally augment ␤-adrenergic tone.Although the inhibition of sympathetic activity may partly account for the benefits observed, there are likely to be, we suggest, additional and important effects on the chronic inflammation seen in chronic heart failure (CHF).It is increasingly appreciated that efferent vagal nerve stimulation can directly and rapidly regulate immune responses.Vagal nerve stimulation can inhibit the release of cytokines like tumor necrosis factor; interleukins-1, -6, and -18 (but not interleukin-10); and intracellular high-mobility group B1 protein.In particular, vagal nerve stimulation protects against endotoxemia 2 and ischemia-reperfusion injury. 3Tracey has termed this the "cholinergic anti-inflammatory pathway" or "the inflammatory reflex." 3 Mechanistically, the process seems to depend on the nicotinic acetylcholine receptor ␣-7 subunit. 4 In edematous human CHF patients, increased levels of proinflammatory endotoxin (LPS) have been detected. 5 Plausibly, we propose that increased levels of LPS may have been present in the studied rats with untreated CHF.These rats were treated from 2 weeks onward.At this time, Ͼ60% had died, and many were severely ill, as indicated by the subsequent 20-week mortality rate of 50% in the sham-treated CHF rats.Therefore, it can be considered that among other properties, vagal stimulation was a highly effective antiinflammatory treatment that was applied to animals with advanced CHF (likely equivalent to New York Heart Association class IV in humans).It is our contention that this study may have demonstrated the potential utility of antiinflammatory and particularly anti-LPS therapies in severe CHF.
Can acute phase proteins predict survival in ventilated patients with acute exacerbation of COPD
Authors: Gamal Agmy, Hoda Maghlouf, Safaa Wafy, Yasser Ahmed, Shahban Radwan
Journal: European Respiratory Journal (2012)

Background:  Factors determining in-hospital mortality of patients ventilated with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are not precisely understood.   PURPOSE:  The aim of this study was to assess the correlation between acute phase proteins [High sensitivity C-reactive protein (CRP) and prealbumin (PA)] and mortality in ventilated patients with COPD.   METHODS:  We evaluated 336 COPD patients with AECOPD and on invasive mechanical ventilation. Detailed clinical evaluation was done daily. Concentration of CRP and PA was measured on admission, 3rd, 8th and 16th day.   RESULTS:  During the study; 237 patients were discharged and 99 died. The difference between the two groups in CRP and PA was significant at admission, 3rd, 8th day and 16th day. In non survivors; there was a significant increase in CRP values with a significant decrease in PA with time (P   CONCLUSIONS:  CRP levels in patients who died was significantly higher on admission, 3rd, 8th and 16th day. A fall in CRP levels on follow up indicated a significantly better prognosis. An increase in the prealbumin level was observed in survivors.   CLINICAL IMPLICATIONS:  Persistently high CRP and low prealbumen in COPD patients on ventilator is associated with poor prognosis. Aggressive treatment of systemic inflammation and malnutrition may improve prognosis. Prediction of survival status may be enhanced by considering arterial oxygen tension, albumin, body mass index, duration of hospitalisation.
The problem with using associations to carry binding information
Authors: Leonidas A. A. Doumas, Keith J. Holyoak, John E. Hummel
Journal: Behavioral and Brain Sciences (2006)

van der Velde &amp; de Kamps argue for the importance of considering the binding problem in accounts of human mental representation. However, their proposed solution fails as a complete account because it represents the bindings between roles and their fillers through associations (or connections). In addition, many criticisms leveled by the authors towards synchrony-based bindings models do not hold.
Association of CAV1/CAV2 Genomic Variants with Primary Open-Angle Glaucoma Overall and by Gender and Pattern of Visual Field Loss
Authors: Stephanie J. Loomis, Jae H. Kang, Robert N. Weinreb, Brian L. Yaspan, Jessica N. Cooke Bailey, Douglas Gaasterland, Terry Gaasterland, Richard K. Lee, Paul R. Lichter, Donald L. Budenz, Yutao Liu, Tony Realini, David S. Friedman, Catherine A. McCarty, Sayoko E. Moroi, Lana Olson, Joel S. Schuman, Kuldev Singh, Douglas Vollrath, Gadi Wollstein, Donald J. Zack, Murray Brilliant, Arthur J. Sit, William G. Christen, John Fingert, Peter Kraft, Kang Zhang, R. Rand Allingham, Margaret A. Pericak-Vance, Julia E. Richards, Michael A. Hauser, Jonathan L. Haines, Louis R. Pasquale, Janey L. Wiggs
Journal: Ophthalmology (2013)
Liposomal local therapy of upper respiratory tract involvement in ANCA associated vasculitis
Authors: Benedikt Hofauer, Clemens Heiser, Naglaa Mansour, Murat Bas, Andreas Knopf
Journal: European Respiratory Journal (2014)

Introduction 

Granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis and microscopic polyangiitis constitude the group of ANCA associated vasculitis (AAV). Ear, nose and throat manifestations are part of the typical clinical presentation of these diseases. Usually, patients are treated with systemic immunomodulatory drugs, mostly based on organ affection. In clinical routine, an insufficient decrease of upper respiratory tract (URT) manifestations during a solely systemic therapeutic concept can repeatedly be observed.

Material and Methods 

Between February 2009 and November 2012 20 patients with AAV were diagnosed in or refered to our department for further treatment. Clinical symptoms and manifestations were measured by the use of international accepted activity scores (BVAS, VDI, FFS). The effect of a local therapy with liposomes for a duration of two months on URT symptoms was prospectively evaluated by using visual analogue scales and standardized questionnaires.

Results 

Within the described collective 100% of patients did show ENT symptoms at the time of initial diagnosis. Every patient did receive immunomodulatory therapy, but in 61.1% of cases there was just slight or no improvement on URT symptoms. After a two-months period of liposomal local therapy, a significant reduction of URT complaints could be observed, both evaluated via visual analogue scales (p<0.001 to p=0.014, depending on the evaluated symptom) and standardized questionnaires (p<0.001).

Conclusions 

The local application of liposomes in addition to a systemic therapy is effective in alleviating upper respiratory tract manifestations in patients with ANCA associated vasculitis.
The Consult Guys - Too Close for Comfort? For How Long Must I Stop This Anticoagulant for an Epidural?
Authors: Geno J. Merli, Howard H. Weitz
Journal: Annals of Internal Medicine (2015)

Web Exclusives20 January 2015The Consult Guys - Too Close for Comfort? For How Long Must I Stop This Anticoagulant for an Epidural?FREEGeno J. Merli, MD and Howard H. Weitz, MDGeno J. Merli, MDSearch for more papers by this author and Howard H. Weitz, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G15-3001 SectionsSupplemental MaterialAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The Consult Guys bring a new perspective to the art and science of medicine with lively discussion and analysis of real-world cases and situations.For more videos from and information on The Consult Guys, visit www.annals.org/ConsultGuys. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Disclosures: Geno J. Merli, MD, reports the following: Research grants/contracts: Bristol-Myers Squibb, Bayer, sanofi-aventis; Consultancies: Bristol-Myers Squibb, Bayer, sanofi-aventis. Howard H. Weitz, MD, reports that he has no financial relationships or interests to disclose. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByAnticoagulation? Antiplatelet? What's the Score?Jonathan Hager, MD 20 January 2015Volume 162, Issue 2Page: CG1KeywordsAnticoagulantsDisclosureResearch grantsResearch reporting guidelines ePublished: 20 January 2015 Issue Published: 20 January 2015 CopyrightCopyright © 2015 by American College of Physicians. All Rights Reserved.Loading ...
Efficacy of sapropterin dihydrochloride (tetrahydrobiopterin, 6R-BH4) for reduction of phenylalanine concentration in patients with phenylketonuria: a phase III randomised placebo-controlled study
Authors: Harvey L Levy, Andrzej Milanowski, Anupam Chakrapani, Maureen Cleary, Philip Lee, Friedrich K Trefz, Chester B Whitley, François Feillet, Annette S Feigenbaum, Judith D Bebchuk, Heidi Christ-Schmidt, Alex Dorenbaum
Journal: The Lancet (2007)
Frequent Mutation of <i>Apc</i> Gene in Rat Colon Tumors and Mucin-Depleted Foci, Preneoplastic Lesions in Experimental Colon Carcinogenesis
Authors: Angelo Pietro Femia, Piero Dolara, Augusto Giannini, Maddalena Salvadori, Annibale Biggeri, Giovanna Caderni
Journal: Cancer Research (2007)

Abstract Mucin-depleted foci (MDF) are microscopic dysplastic lesions induced in the colon of rodents by specific colon carcinogens. Most MDF show Wnt pathway activation, whereas only a subset shows mutations in the Ctnnb1 gene, coding for β-catenin. Because Apc is a member of the Wnt pathway and the most frequent mutated gene in human colon cancer, we tested whether MDF harbor Apc mutations. F344 rats were treated twice with 150 mg/kg of 1,2-dimethylhydrazine. After 15 or 28 weeks, MDF, aberrant crypt foci (ACF), and tumors were collected. We screened a segment of the Apc gene comprising the region homologous to the mutation cluster region (MCR) of human APC, which frequently shows mutations in experimental colon tumors. Mutations were identified by PCR amplification and sequencing in 6:24 MDF (25%), 7:23 tumors (30%), 0:24 ACF (0%). Most of the mutations (92%) in MDF and tumors were localized in a region upstream from the MCR. All mutations were single-base substitutions and mainly formed by G:C → A:T and C:G → T:A transitions. The pattern of nucleotide changes was similar in MDF and tumors, and, interestingly, the same mutation in codon 1047 was found in two MDF and in three tumors. Four out of the six mutations found in MDF were nonsense mutations, and two were missense. All mutations in tumors determined a protein truncation. These results show that Apc mutations are present in MDF with a frequency similar to that of tumors, strengthening the evidence that they are precancerous lesions in colon carcinogenesis. [Cancer Res 2007;67(2):445–9]
hnRNP K Is a Haploinsufficient Tumor Suppressor that Regulates Proliferation and Differentiation Programs in Hematologic Malignancies
Authors: Miguel Gallardo, Hun Ju Lee, Xiaorui Zhang, Carlos Bueso-Ramos, Laura R. Pageon, Mark McArthur, Asha Multani, Aziz Nazha, Taghi Manshouri, Jan Parker-Thornburg, Inmaculada Rapado, Alfonso Quintas-Cardama, Steven M. Kornblau, Joaquin Martinez-Lopez, Sean M. Post
Journal: Cancer Cell (2015)
THE INVOLVEMENT OF LACTOFERRIN IN THE HYPOSIDEREMIA OF ACUTE INFLAMMATION
Authors: Jacques L. van Snick, Pierre L. Masson, Joseph F. Heremans
Journal: The Journal of Experimental Medicine (1974)

The hyposideremia of inflammation was found to be based on a three-step mechanism involving lactoferrin, the iron-binding protein from the specific granules of neutrophilic leukocytes. (a) Lactoferrin is Released from Neutrophils in an Iron-Free Form. When phagocytosis was induced in neutrophils by zymosan or bacteria, lactoferrin was recovered in the incubation medium together with other constituents of the specific granules, such as alkaline phosphatase and lysozyme. Lactoferrin extracted from leukocytes was able to bind the amount of iron corresponding to its theoretical iron-binding capacity. After injection of endotoxin into rats, lactoferrin was detected in various tissues where it was normally absent, or in the plasma when the reticuloendothelial system (RES) had previously been blocked by injections of India ink or aggregated albumin. (b) Lactoferrin is Able to Remove the Iron from Transferrin. Significant exchange of iron from transferrin to lactoferrin was observed in vitro only at a pH below 7.0 or in the presence of a high concentration of citrate. However, the fast elimination of lactoferrin in vivo, when saturated with iron, might account for the observed transfer of iron to endogenous or administered apolactoferrin. Intravenous injection of human apolactoferrin into rats caused a marked decrease of the plasma iron level. The kinetics of this process, as well as controls with other proteins, ruled out the possibility of a secondary inflammatory effect due to phlogogenic contaminants. (c) Fe-Lactoferrin is Taken-up by the RES. By immunofluorescence, lactoferrin was shown to be bound and ingested by monocytes. The rate of elimination of human Fe-lactoferrin injected into rats was particularly fast when compared to that of human apolactoferrin, succinylated Fe-lactoferrin, or other human proteins. Blockade of the RES slowed down the rate of clearance of Fe-lactoferrin and was also found to retard the elimination of endogenous rat lactoferrin released by endotoxin. These experiments suggest the existence of specific receptors for Fe-lactoferrin on the membrane of macrophages.
Is balance impaired by recurrent sprained ankle?
Authors: E Isakov, J Mizrahi
Journal: British Journal of Sports Medicine (1997)

OBJECTIVE: To evaluate uninjured and recurrent sprained ankles during single leg standing, both with and without visual input, and the contribution of related proprioceptive feedback in this event. METHODS: A force measuring system was used for monitoring reaction forces in the anteroposterior and mediolateral directions during single leg standing. Differences between selected variables obtained in the uninjured and sprained ankles were analysed using two way analysis of variance. RESULTS: Foot-ground reaction forces in both anteroposterior and mediolateral directions were the same in normal and sprained ankles of each subject while standing with either open or closed eyes. However, standing with closed eyes, irrespective of the ankle status, always produced significantly higher reaction forces than those obtained with open eyes (P &lt; 0.05). CONCLUSIONS: The amount of postural sway during single leg standing is similar in the chronically sprained and the uninjured ankle joint.