tbuckley/cabot-search huggingface dataset:
Skin test concentrations for systemically administered drugs – an<scp>ENDA</scp>/<scp>EAACI</scp>Drug Allergy Interest Group position paper
Authors: K. Brockow, L. H. Garvey, W. Aberer, M. Atanaskovic‐Markovic, A. Barbaud, M. B. Bilo, A. Bircher, M. Blanca, B. Bonadonna, P. Campi, E. Castro, J. R. Cernadas, A. M. Chiriac, P. Demoly, M. Grosber, J. Gooi, C. Lombardo, P. M. Mertes, H. Mosbech, S. Nasser, M. Pagani, J. Ring, A. Romano, K. Scherer, B. Schnyder, S. Testi, M. Torres, A. Trautmann, I. Terreehorst
Journal: Allergy (2013)

Abstract Skin tests are of paramount importance for the evaluation of drug hypersensitivity reactions. Drug skin tests are often not carried out because of lack of concise information on specific test concentrations. The diagnosis of drug allergy is often based on history alone, which is an unreliable indicator of true hypersensitivity.To promote and standardize reproducible skin testing with safe and nonirritant drug concentrations in the clinical practice, the E uropean N etwork and E uropean A cademy of A llergy and C linical I mmunology ( EAACI ) Interest Group on Drug Allergy has performed a literature search on skin test drug concentration in MEDLINE and EMBASE , reviewed and evaluated the literature in five languages using the GRADE system for quality of evidence and strength of recommendation. Where the literature is poor, we have taken into consideration the collective experience of the group.We recommend drug concentration for skin testing aiming to achieve a specificity of at least 95%. It has been possible to recommend specific drug concentration for betalactam antibiotics, perioperative drugs, heparins, platinum salts and radiocontrast media. For many other drugs, there is insufficient evidence to recommend appropriate drug concentration. There is urgent need for multicentre studies designed to establish and validate drug skin test concentration using standard protocols. For most drugs, sensitivity of skin testing is higher in immediate hypersensitivity compared to nonimmediate hypersensitivity.
S87 A Functional Comparison Of Neonatal And Adult Neutrophil Responses To Respiratory Syncytial Virus
Authors: G. Saint, B. Flanagan, R. Corkhill, R. Smyth, P. McNamara
Journal: Thorax (2014)

<h3>Introduction and objectives</h3> Respiratory Syncytial Virus (RSV) is a major cause of lower respiratory tract infection during infancy. Neutrophils are the predominant cell type within the RSV-infected airway, 80% of inflammatory cells from BAL of intubated infants being neutrophils. Despite extensive research unpicking innate viral responses to RSV little is known about the specific role the neutrophil plays. The aim of this work was to investigate the response of neutrophils to RSV using an <i>in vitro</i> model utilising neutrophils from adult volunteers. To investigate whether relative immaturity of infant neutrophils leads to impaired responses we are now comparing adult neutrophils with neonatal neutrophils, isolated from cord blood. <h3>Methods</h3> Highly purified neutrophils from whole blood of healthy adult donors were incubated with RSV. Samples were taken at 2, 4, and 20 h for QT-PCR of RSV N gene, western blot analysis and cytospin slides for confocal imaging of RSV F protein. Experiments were then replicated using neutrophils purified from cord blood, collected from the placenta following elective caesarean section, of healthy term neonates. Supernatants were stored for measurement of the cytokine response of the neutrophil to RSV. <h3>Results</h3> Uptake of RSV by adult neutrophils was shown by both western blot and quantitative RT-PCR. Maximal uptake was at 4 h with a reduction by 20 h. Confocal microscopy was undertaken, using a primary monoclonal antibody to RSV fusion protein. This showed that RSV was internalised inside the cytoplasm in a distribution suggestive of endosomal uptake <i>(see figure)</i>. Preliminary data suggests that neonatal neutrophils are also capable of this viral uptake but work is ongoing to determine differences between the two models. <h3>Conclusions</h3> We have shown that neutrophils may be involved in viral clearance as part of the immune response to viral invasion. They appear to take up virus with kinetics suggestive of endocytosis. Work is ongoing to establish the mechanism of entry using a panel of inhibitors. Initial results would suggest that neonatal neutrophils may respond similarly but work continues to establish whether this is the case and if there is any functional impairment that may explain infants’ propensity to severe disease.
Colorectal cancer screening in asymptomatic populations.
Authors: A R Hart, A C Wicks, J F Mayberry
Journal: Gut (1995)

Colorectal cancer is the second commonest cause of cancer death in the UK. An effective national screening programme is urgently required to reduce the substantial morbidity and mortality from the disease. The success of any screening programme will depend on the screening test detecting early Dukes's A carcinomas and adenomatous polyps. Prognosis is directly related to tumour staging and a proportion of carcinomas are thought to arise from polyps. Two screening methods exist--faecal occult blood testing and sigmoidoscopy. Large trials of faecal occult blood testing show that it detects more early lesions than in patients presenting with symptoms, but whether this reduces mortality is not yet confirmed and lack of sensitivity for cancers and polyps may ultimately limits its usefulness. The role of sigmoidoscopy in screening, particularly flexible sigmoidoscopy, has not been fully investigated. Flexible sigmoidoscopy has a greater sensitivity for distal lesions than stool testing and a randomised controlled trial of its efficacy is planned in Britain. Compliance with screening is essential to ensure its cost effectiveness in both health and economic terms. Large trials of faecal occult blood testing conducted over several years achieved compliance rates in excess of 60%, although in smaller studies these are often much less. Women frequently participate more than men. There are many reasons for non-compliance including lack of appreciation of the concept of asymptomatic illness and fear of the screening tests and cancer itself. Colorectal cancer screening is relatively cheap compared with breast and cervical cancer screening. Provisional cost estimates suggest that the amount spent to detect or prevent cancer by screening is similar to the amount required to treat a symptomatic patient.
Performance Measurement in Chronic Kidney Disease
Authors: Kimberly A. Smith, Rodney A. Hayward
Journal: Journal of the American Society of Nephrology (2011)

Do Americans receive high-value health care? Value only improves by advancing key indicators in one of two directions: increasing quality, decreasing cost, or both. In the face of unyielding mortality rates and the relentless expense of end-stage renal disease, government agencies and professional organizations are now focusing on new quality measures for patients with advancing chronic kidney disease. These performance measures are in early stages of refinement but reflect efforts of payers to slow the incidence of progressive renal disease across the population. To improve quality of care, one must study the performance measures themselves and determine how to capture the necessary data efficiently, identify the appropriate patients for measurement, and assign accountability to providers. Here, we discuss the challenges of doing this well.
Progression of Human Bronchioloalveolar Carcinoma to Invasive Adenocarcinoma Is Modeled in a Transgenic Mouse Model of K-ras–Induced Lung Cancer by Loss of the TGF-β Type II Receptor
Authors: Alain C. Borczuk, Marieta Sole, Ping Lu, Jinli Chen, May-Lin Wilgus, Richard A. Friedman, Steven M. Albelda, Charles A. Powell
Journal: Cancer Research (2011)

Clinical investigations have suggested that repression of the TGF-β type II receptor (TβRII) may be an important step in progression of lung adenocarcinoma from an indolent in situ state to a frank invasive carcinoma. To test this hypothesis, we compared the effects of deleting the murine homolog of this receptor (Tgfbr2) in a mouse model of mutant K-ras-induced lung carcinoma, which normally induces the formation of multifocal tumors of low invasive potential. In this model, loss of Tgfbr2 induced a highly invasive phenotype associated with lymph node metastasis and reduced survival. Tumor-associated stromal cells displayed an immunosuppressive profile marked by increased numbers of B and T cells. Moreover, tumor stromal cell profiling revealed a developmental TGF-β response profile that associated with a collagenized extracellular matrix and increased invasion of TGF-β nonresponsive tumor cells. Together, these results suggest that our KrasTgfbr2(-/-) mouse model of invasive lung carcinoma mirrors the genomic response and clinical progression of human lung adenocarcinoma, recapitulating changes in lung stromal pathways that occur in the tumor microenvironment during malignant progression in this disease.
Response to Adenosine Differentiates Focal From Macroreentrant Atrial Tachycardia
Authors: Sei Iwai, Steven M. Markowitz, Kenneth M. Stein, Suneet Mittal, David J. Slotwiner, Mithilesh K. Das, Jennifer D. Cohen, Steven C. Hao, Bruce B. Lerman
Journal: Circulation (2002)

We previously proposed that adenosine has mechanism-specific effects on atrial tachycardia (AT), such that adenosine terminates AT attributable to triggered activity, transiently suppresses automatic rhythms, and has no effect on macroreentrant AT. This, however, remains controversial, because other studies have reported that adenosine terminates reentrant AT. To clarify this issue, we used 3D electroanatomic mapping to delineate the tachycardia circuit and thereby determine whether the response to adenosine differentiates focal from macroreentrant AT.We examined the effect of adenosine on 43 ATs in 42 consecutive patients (59+/-15 years of age; 26 female) who received adenosine during tachycardia and whose mechanism of AT was characterized by pharmacological perturbation, entrainment, 3D electroanatomic mapping, and results of radiofrequency ablation. Eight tachycardias were macroreentrant (noncavotricuspid isthmus-dependent), and 35 ATs were focal (either triggered or automatic). Adenosine administered during AT (at doses sufficient to result in AV block) terminated or transiently suppressed focal AT in 33 of 35 cases, whereas 8 of 8 macroreentrant ATs were adenosine insensitive (P<0.001). Twenty-eight of 35 focal ATs were located along the crista terminalis or tricuspid annulus.The response of AT to adenosine can immediately differentiate atrial tachycardia arising from a focal source from that attributable to macroreentry. This finding can be exploited to facilitate developing a focused, strategic ablative approach at the onset of a procedure.
The role of L-type calcium current in the generation of repolarization-induced contraction in cardiac myocytes
Authors: R Egdell
Journal: Cardiovascular Research (2000)

Early experiments into the arrhythmogenic transient inward current frequently showed apparent coupling of this current to repolarization from a depolarizing voltage clamp step. Calcium transients have subsequently been shown to couple to such repolarization and are the result of calcium release from the sarcoplasmic reticulum. We have investigated whether this phenomenon is due to calcium entry via non-inactivated calcium channels or to voltage-activated SR release.Voltage clamp steps were imposed on isolated guinea pig and rabbit cardiac myocytes. Calcium release was monitored by tracking cell contraction. L-type calcium current at the moment of repolarization was manipulated by the rapid application of 2 mM cadmium or 10 mM calcium.Repolarization-induced contraction was abolished by the rapid application of 2 mM cadmium immediately prior to repolarization, and was augmented by the rapid change of extracellular calcium concentration from 2 mM to 10 mM immediately prior to repolarization. There is no evidence of coupling of drive train-induced aftercontractions to repolarization from the final action potential of the drive train and 2 mM cadmium does not alter the appearance or timing of these aftercontractions. Simulation of phase 1 repolarization in the mammalian cardiac action potential decreases rather than increases twitch amplitude.Repolarization-induced contraction results from calcium entry through non-inactivated calcium channels, not from voltage-activated release. It plays no physiological role in contributing to the stimulated twitch and no pathological role in generating drive train-induced aftercontractions.
Serum LDH and exercise capacity in COPD
Authors: M A Spruit, H J Pennings, J D Does, G M Moller, P P Janssen, E F M Wouters
Journal: Thorax (2008)

<h3>Abstract</h3> Swine influenza virus (SIV) is a significant burden on the pork industry and threat to human health due to its zoonotic potential. Here, we utilized epigraph, a computational algorithm, to design a universal swine H3 (swH3) influenza vaccine. The epigraph hemagglutinin proteins were delivered using an Adenovirus type 5 vector and compared to a wild type hemagglutinin and the commercial inactivated vaccine, FluSure. In mice, epigraph vaccination led to significant cross-reactive antibody and T-cell responses against a diverse panel of swH3 isolates. Epigraph vaccination also reduced weight loss and lung viral titers in mice after challenge with three divergent swH3 viruses. Vaccination studies in swine, the target species for this vaccine, showed stronger levels of cross-reactive antibodies and T-cell responses after immunization with epigraph vaccine compared to the wild type and FluSure vaccines. In both murine and swine models, epigraph vaccination showed superior cross-reactive immunity that should be further investigated as a universal swH3 vaccine.
Postischemic recovery of mechanical performance and energy metabolism in the presence of left ventricular hypertrophy. A 31P-MRS study.
Authors: P T Buser, J Wikman-Coffelt, S T Wu, N Derugin, W W Parmley, C B Higgins
Journal: Circulation Research (1990)

The present study was undertaken to define the effects of left ventricular hypertrophy on postischemic recovery of myocardial performance and high energy phosphate metabolism. Hemodynamics and 31P-magnetic resonance spectra were monitored simultaneously in the isolated Langendorff-perfused rat heart during 30 minutes of ischemia and 30 minutes of reperfusion. Left ventricular hypertrophy was produced by either suprarenal aortic constriction or chronic thyroxine administration. In chronic pressure overload hypertrophy, minimal coronary resistance was significantly higher (p less than 0.001) and the loss of purine nucleosides in the coronary effluent during early reperfusion significantly larger (p less than 0.001) compared with both normal hearts and thyroxine-induced hypertrophied hearts. Postischemic recovery of the baseline values for left ventricular developed pressure and phosphorylation potential was 43 +/- 4% and 82 +/- 4%, respectively, in chronic pressure overload hypertrophied hearts; 86 +/- 4% and 91 +/- 3%, respectively, in normal hearts (chronic pressure overload hypertrophy versus normal hearts, p less than 0.001 and p less than 0.05); and 100 +/- 4% and 98 +/- 2%, respectively, in thyroxine-induced hypertrophied hearts (normal hearts versus thyroxine-induced hypertrophied hearts, p less than 0.05 and p less than 0.05). Recovery after reperfusion was not related to intracellular pH, ATP, phosphocreatine, or inorganic phosphate levels during ischemia. Also, recovery was not related to developed pressure or oxygen consumption before ischemia. However, recovery was inversely related to coronary resistance and directly related to coronary flow before ischemia. Thus, functional and/or anatomic alterations of the coronary vascular bed and a greater loss of purine nucleosides during reperfusion are likely responsible for the attenuated compensatory response to ischemia and reperfusion in left ventricular hypertrophy induced by chronic pressure overload. On the other hand, the excess muscle mass per se does not seem to alter recovery, since thyroxine-induced myocardial hypertrophied hearts responded at least as well as normal hearts.
MPs criticise "diluted" priority for cancer services over past two years
Authors: A. O'Dowd
Journal: BMJ (2015)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following MPs criticise “diluted” priority for cancer services over past two years Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
McArdle's disease heterozygotes. Metabolic adaptation assessed using 31P-nuclear magnetic resonance.
Authors: R T Bogusky, R G Taylor, L J Anderson, K L Angelos, J S Lieberman, D A Walsh
Journal: Journal of Clinical Investigation (1986)

Two daughters of a propositus with documented McArdle's disease were shown by enzyme assay, gel electrophoresis, and immunoblotting to be partially deficient in skeletal muscle phosphorylase and, presumably, heterozygous for the trait. Both exhibited only the adult form of the skeletal muscle isozyme. By 31P-nuclear magnetic resonance, both heterozygotes showed a greater production of acid during fully aerobic exercise than when blood flow was occluded in ischemic exercise. This pattern is in contrast to that of control subjects, where there is significantly greater acid production in ischemic versus aerobic exercise, and distinct from that of phosphorylase-negative patients in which no acid is produced in either circumstance. We suggest that these heterozygotes may have adapted to their diminished phosphorylase by enhancing utilization of plasma glucose. If so, this mechanism could account for the observation that most of the symptoms of McArdle's disease are often manifest only in adulthood. These studies also show that although there are very high concentrations of phosphorylase in skeletal muscle (approximately 2% of the soluble protein), such a high level is essential for normal muscle glycogenolysis.
Deconstructing neural constructivism
Authors: Olaf Sporns
Journal: Behavioral and Brain Sciences (1997)

Activity-dependent processes play an active role in shaping the structure of neuronal circuitry and therefore contribute to neural and cognitive development. Neural constructivism claims to be able to account for increases in the complexity of cognitive representations in terms of directed growth of neurons. This claim is overstated, rests on biased nterpretations of the evidence, and is based on serious misapprehensions of the nature of somatic variation and selection.
The importance of dyspnea and airflow limitation for anxiety and depression in COPD
Authors: Ricardo Coelho, Ana Sofia Santos, Raquel Rosa, Dionísio Maia, Tiago Sá, Vânia Caldeira, Luísa Semedo, João Cardoso
Journal: European Respiratory Journal (2014)

Background: Depression and anxiety are important and frequent comorbidities in COPD, leading to increased morbidity and impaired quality of life.

Aim: Evaluate the presence of anxiety and depression in the COPD patients and their relation to the airflow limitation severity, dyspnea and exacerbations.

Methods: 100 consecutive COPD patients were stratified according to GOLD (GOLD groups and spirometric stages). Dyspnea was assessed using the Modified Medical Research Council Dyspnea Scale (mMRC). The presence of anxiety and depression was evaluated through the Hospital Anxiety and Depression Scale.

Results: The mean age was 65±9 years, 85% were male. The distribution of anxiety/depression according to spirometric stages or GOLD groups (using mMRC) is shown in the tables below:

View this table:



View this table:



The exacerbation history and its relation to anxiety/depression showed that: the 7 patients of group C who had at least 2 exacerbations in the previous year, none had anxiety/depression; from the 27 patients of group D who had at least 2 exacerbations in the previous year, 52% had anxiety and 63% had depression.

Conclusion: Anxiety and depression are two significant comorbidities of COPD, being the severity of dyspnea (mMRC≥2) a very important factor for both (groups B,D). Also, the frequency of anxiety and depression was higher with worsening airflow limitation and the exacerbation history had a contribution in the cases where significant dyspnea was present.
Hepatocyte Growth Factor Promotes Cancer Cell Migration and Angiogenic Factors Expression: A Prognostic Marker of Human Esophageal Squamous Cell Carcinomas
Authors: Yi Ren, Brian Cao, Simon Law, Yi Xie, Ping Yin Lee, Leo Cheung, Yongxong Chen, Xin Huang, Hiu Man Chan, Ping Zhao, John Luk, George Vande Woude, John Wong
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, c-Met, play important roles in tumor development and progression. In this study, we measured the serum HGF levels in patients with esophageal squamous cell carcinoma (ESCC) to evaluate its relationships with clinicopathologic features and the role of HGF in ESCC. Experimental Design: One hundred and forty-nine patients with ESCC were studied. Pretherapy serum was collected and ELISA was used to detect the concentrations of HGF, vascular endothelial growth factor (VEGF), and interleukin 8 (IL-8). The function of HGF was shown by invasion chamber assay. Results: Pretherapy serum HGF was found to be significantly higher in patients with ESCC than in control subjects. The levels of HGF correlated significantly with advanced tumor metastasis stage and survival. Multivariate analyses showed that serum HGF level in cell migration was an independent prognostic factor. Increased HGF serum levels correlated positively with serum levels of VEGF and IL-8. Our results also showed that HGF was overexpressed in ESCC tissues and cell lines. In vitro study showed that HGF could stimulate ESCC cell to express VEGF and IL-8 and markedly enhance invasion and migration of ESCC cells. Furthermore, HGF-induced IL-8 and VEGF expression was dependent on extracellular signal-regulated kinase signaling pathways. The inhibition of extracellular signal-regulated kinase activation reduced HGF-mediated IL-8 and VEGF expression. Conclusions: Our results suggest that serum HGF may be a useful biomarker of tumor progression and a valuable independent prognostic factor in patients with ESCC. HGF may be involved in the progression of ESCC as an autocrine/paracrine factor via enhancing angiogenesis and tumor cell invasion and migration.
Effectiveness of Lead Cap in Radiation Protection of Head in the Cardiac Catheterization Laboratory
Authors: Eser Durmaz, Bilgehan Karadağ, Barış İkitimur, Burçak Kılıçkıran Avcı, Hüseyin Altuğ Çakmak, Özge Özden Tok, Zeki Öngen
Journal: Journal of the American College of Cardiology (2013)