tbuckley/cabot-search huggingface dataset:
(18) Xanthoma tuberosum and gout
Authors: J.B. Lyon
Journal: British Journal of Dermatology (1975)

Journal Article (18) Xanthoma tuberosum and gout Get access J.B. Lyon J.B. Lyon Ipswich Hospital Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 93, Issue s11, 1 July 1975, Pages 57–58, https://doi.org/10.1111/j.1365-2133.1975.tb06800.x Published: 01 July 1975
QT prolongation through hERG K<sup>+</sup> channel blockade: Current knowledge and strategies for the early prediction during drug development
Authors: Maurizio Recanatini, Elisabetta Poluzzi, Matteo Masetti, Andrea Cavalli, Fabrizio De Ponti
Journal: Medicinal Research Reviews (2004)

Abstract Prolongation of the QT interval of the electrocardiogram is a typical effect of Class III antiarrhythmic drugs, achieved through blockade of potassium channels. In the past decade, evidence has accrued that several classes of drugs used for non‐cardiovascular indications may prolong the QT interval with the same mechanism (namely, human ether‐à‐go‐go‐related gene (hERG) K + channel blockade). The great interest in QT prolongation is because of several reasons. First, drug‐induced QT prolongation increases the likelihood of a polymorphous ventricular arrhythmia (namely, torsades de pointes , TdP), which may cause syncope and degenerate into ventricular fibrillation and sudden death. Second, the fact that several classes of drugs, such as antihistamines, fluoroquinolones, macrolides, and neuroleptics may cause the long QT syndrome (LQTS) raises the question whether this is a class effect (e.g., shared by all agents of a given pharmacological class) or a specific effect of single agents within a class. There is now consensus that, in most cases, only a few agents within a therapeutic class share the ability to significantly affect hERG K + channels. These compounds should be identified as early as possible during drug development. Third, QT prolongation and interaction with hERG K + channels have become surrogate markers of cardiotoxicity and have received increasing regulatory attention. This review briefly outlines the mechanisms leading to QT prolongation and the different strategies that can be followed to predict this unwanted effect. In particular, it will focus on the approaches recently proposed for the in silico screening of new compounds. © 2004 Wiley Periodicals, Inc.
Do we need new asthma control tests?
Authors: Jean Bousquet, Arnaud Bourdin, Pascal Demoly
Journal: European Respiratory Journal (2014)

The assessment of asthma control is pivotal to the evaluation of treatment response. The National Asthma Education and Prevention Program (NAEPP) guidelines and the 2006 update of the Global Initiative for Asthma (GINA) proposed to use asthma control (control of manifestations of the disease) to guide treatment [1]. It is important in clinical practice to identify patients with uncontrolled asthma, since they have a risk of exacerbations [2]. Asthma control may be assessed using several approaches [3, 4]. There is no gold standard for the assessment of asthma control, which is usually considered to be a continuum from total to poor control [3–5]. The concept of composite measures for the assessment of asthma control is based on 1) the generally poor correlation between different domains of asthma, 2) the lack of a single gold standard and 3) the use of multiple end-points providing a more complete picture of asthma control than a single end-point [3, 4]. The GINA guidelines propose a questionnaire for recent events and exacerbations over the past year [1]. Results of pulmonary function tests are added to the definition. However, albeit recommended, pulmonary function tests are unavailable in most practices throughout the world. The asthma control questionnaires ( e.g. the Asthma Control Questionnaire (ACQ) and Asthma Control Test (ACT)) are based on a …
Pleural diseases related to metastatic malignancies
Authors: SA Sahn
Journal: European Respiratory Journal (1997)

Pleural effusions associated with malignancy (either malignant or paramalignant) pose diagnostic and therapeutic dilemmas for the clinician. This article reviews the common causes of malignant and paramalignant pleural effusions, pathogenesis, clinical presentation, chest radiography, pleural fluid characteristics, diagnosis, prognosis, and treatment. Talc, used either by poudrage or slurry, is the most effective agent used for pleurodesis. Talc, which needs to be sterilized, has no clinically important immediate, short-term or long-term adverse effects.
THU0546 Hand Assessment with the E-Cone in Rheumatoid Arthritis and Hand Osteoarthritis
Authors: N. van Merendonk, V. van Alebeek, L. Spreeuwers, D. Spreeuwers, P. J. Kroon, L. Roorda, J. Dekker, A. F. Hoeksma
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Rheumatoid arthritis (RA) is a systemic inflammatory, progressive disease resulting in deformities of the hand. Besides synovitis, tenosynovitis of the extrinsic flexor tendons is one of the initial features of RA, leading to friction and consequently to an imbalanced coordination of the hand muscles. This phenomenon is also seen in patients with hand osteoarthritis (HOA). For the treatment of RA and HOA, focused on optimal hand coordination, feedback regarding the coordination of the intrinsic and extrinsic muscles is essential. We have developed a new device to provide this feedback, by means of pressure sensors attached to a cone that register and visualize the distribution of hand pressure on a screen: the E-cone (figure 1). In clinical practice, the E-cone has been successfully used as a treatment device; patients can easily interpret the image on the screen, and use this as cue to improve their handgrip. In order to implement the E-cone as a diagnostic device, inter- and intra-observer reliability has to be determined. <h3>Objectives</h3> To assess the reliability of the E-cone in RA or HOA patients and healthy subjects, while assessing the handgrip pattern and pressure distribution. <h3>Methods</h3> This study included patients with RA or HOA, treated in the hand rehabilitation team, and healthy subjects without impairments. The subjects raised the E-cone with each hand successively. This assessment was filmed with a webcam. The handgrip pattern and the pressure distribution were assessed twice, using a 5-point Numeric Rating Scale by two independent assessors separately, using the film for the assessment of the handgrip pattern. The inter- and intra-rater reliability were calculated via intra-class correlation (ICC). <h3>Results</h3> Fifty participants (9 RA, 17 HOA and 24 healthy subjects) were assessed; mean age 49.8 years (59.8, 64.4 and 35.7), 88% females. The inter- and intra-rater reliability of the handgrip pattern were in moderate agreement with intra-class correlations of 0.48 and 0.49 respectively. The inter- and intra-rater reliability of the pressure distribution were in fair agreement, both with an intra-class correlation of 0.38. <h3>Image/graph:</h3> <h3>Conclusions</h3> Although the E-cone can easily and successfully be used as a treatment device in restoring handgrip coordination and facilitating tendon gliding in stenosing tenosynovitis, the device can not yet be used as a diagnostic tool. <h3>Disclosure of Interest</h3> None Declared
The Bronchitis Randomized On NAC Cost-Utility Study (BRONCUS): hypothesis and design
Authors: M. Decramer, P.N.R. Dekhuijzen, T. Troosters, C. van Herwaarden, M. Rutten-van Mölken, C.P.O. van Schayck, D. Olivieri, I. Lankhorst, A. Ardia
Journal: European Respiratory Journal (2001)

Chronic obstructive pulmonary disease (COPD) is an irreversible disorder characterized by airflow obstruction and a progressive decline in forced expiratory volume in one second (FEV1). At present, no treatment except quitting smoking appears to affect the progression of the disease. Oxidative stress has been implicated in its pathogenesis. The Bronchitis Randomized on NAC Cost-Utility Study (BRONCUS) is a phase III, randomized, double-blind, placebo-controlled, parallel group, multicentre study designed to assess the effectiveness of the antioxidant agent N-acetylcysteine (NAC) in altering the decline in FEV1, exacerbation rate, and quality of life in patients with moderate to severe COPD. In addition, cost-utility of the treatment will be estimated. Patients will be followed for 3 yrs and evaluated every 3 months. The necessary sample size to demonstrate an effect on the decline in FEV1 of 20 mL x yr(-1) was estimated to be 478 patients. Five hundred and twenty-three patients with moderate to severe COPD were recruited from 10 European countries from June 1, 1997-December 31, 1999. They were 63+/-8 yrs old and consisted of 243 (46%) current smokers and 280 (54%) exsmokers. Patients had on the average 4.9+/-1.6 exacerbations during the last 2 yrs. Postbronchodilator FEVI averaged 57+/-9% and the reversibility after 400 microg of Salbutamol averaged 4+/-4% predicted. The final results of the trial will be available in about 2 yrs. The study will provide objective data on the effects of N-acetylcysteine on outcome variables in chronic obstructive pulmonary disease.
Evaluation of the solitary pulmonary nodule by positron emission tomography imaging
Authors: T Bury, A Dowlati, P Paulus, JL Corhay, T Benoit, JM Kayembe, R Limet, P Rigo, M Radermecker
Journal: European Respiratory Journal (1996)

Current noninvasive imaging methods are not sufficiently reliable for accurate detection of malignancy in most solitary pulmonary nodules (SPNs). Positron emission tomography (PET) using 18-fluorodeoxyglucose (FDG), showing increased FDG uptake and retention in malignant cells, has proved useful to differentiate malignant from benign tissue and could, therefore, contribute to the evaluation of the SPN. We performed a prospective study of 50 patients referred to the Pneumology Department with unclear diagnoses of SPN after conventional radiological screening. PET study was performed on each subject before an invasive procedure was proposed. Thirty three patients had a malignant nodule and 17 had a benign nodule. The mean size of malignant nodule was 3 cm (range 1.5-4.5 cm). All showed a marked increase in 18-FDG uptake. The mean size of benign nodule was 1.8 cm (range 0.5-3.5 cm). PET imaging showed the absence of 18-FDG uptake and correctly identified 15 of 17 benign nodules. There was two false-positive cases with a moderate increase in 18-FDG uptake (1 postprimary tuberculosis; and 1 anthracosilicotic nodule with nonspecific inflammation). At present, the sensitivity and specificity of the method are 100 and 88%, respectively. The positive and negative predictive values of PET imaging for SPNs are 94 and 100%, respectively. Our preliminary results demonstrate that PET-FDG imaging is a noninvasive technique, which appears highly accurate in differentiating malignant SPN from benign SPN.
Effect of Silibinin on the Growth and Progression of Primary Lung Tumors in Mice
Authors: Rana P. Singh, Gagan Deep, Manesh Chittezhath, Manjinder Kaur, Lori D. Dwyer-Nield, Alvin M. Malkinson, Rajesh Agarwal
Journal: JNCI Journal of the National Cancer Institute (2006)

Silibinin, a flavanone from milk thistle, inhibits the growth of tumors in several rodent models. We examined the effects of dietary silibinin on the growth, progression, and angiogenesis of urethane-induced lung tumors in mice.A/J mice (15 per group) were injected with urethane (1 mg/g body weight) or saline alone and fed normal diets for 2 weeks, after which they were fed diets containing different doses of silibinin (0%-1% [wt/wt] silibinin) for 18 or 27 weeks. Immunohistochemistry and Western blot analysis were used to examine angiogenesis and enzymatic markers of inflammation, proliferation, and apoptosis. All statistical tests were two-sided.Urethane-injected mice exposed to silibinin had statistically significantly lower lung tumor multiplicities than urethane-injected mice fed the control diet lacking silibinin (i.e., control mice). Mice that received urethane and 1% (wt/wt) dietary silibinin for 18 weeks had 93% fewer large (i.e., 1.5-2.5-mm-diameter) lung tumors than control mice (mean number of tumors/mouse: 27 in the urethane group versus 2 in the urethane + 1% silibinin group, difference = 25 tumors/mouse, 95% confidence interval [CI] = 13 to 37 tumors/mouse, P = .005). Lung tumors of silibinin-fed mice had 41%-74% fewer cells positive for the cell proliferation markers proliferating cell nuclear antigen and cyclin D1 than lung tumors of control mice. Tumor microvessel density was reduced by up to 89% with silibinin treatment (e.g., 56 microvessels/400x field in tumors from control mice versus 6 microvessels/400x field in tumors from urethane + 1% silibinin-treated mice [difference = 50 microvessels/400x field, 95% CI = 46 to 54 microvessels/400x field; P<.001]). Silibinin decreased lung tumor expression of vascular endothelial growth factor (VEGF) and of inducible nitric oxide synthase and cyclooxygenase-2, two enzymes that promote lung tumor growth and progression by inducing VEGF expression.Silibinin inhibits lung tumor angiogenesis in an animal model and merits investigation as a chemopreventive agent for suppressing lung cancer progression.
Immunogenicity of bivalent types 1 and 3 oral poliovirus vaccine: a randomised, double-blind, controlled trial
Authors: Roland W Sutter, T Jacob John, Hemant Jain, Sharad Agarkhedkar, Padmasani Venkat Ramanan, Harish Verma, Jagadish Deshpande, Ajit Pal Singh, Meghana Sreevatsava, Pradeep Malankar, Anthony Burton, Arani Chatterjee, Hamid Jafari, R Bruce Aylward
Journal: The Lancet (2010)
Angiotensin II Stimulates Vacuolar H+-ATPase Activity in Renal Acid-Secretory Intercalated Cells from the Outer Medullary Collecting Duct
Authors: Florina Rothenberger, Ana Velic, Paul A. Stehberger, Jana Kovacikova, Carsten A. Wagner
Journal: Journal of the American Society of Nephrology (2007)

Final urinary acidification is mediated by the action of vacuolar H<sup>+</sup>-ATPases expressed in acid-secretory type A intercalated cells (A-IC) in the collecting duct. Angiotensin II (AngII) has profound effects on renal acid-base transport in the proximal tubule, distal tubule, and collecting duct. This study investigated the effects on vacuolar H<sup>+</sup>-ATPase activity in A-IC in freshly isolated mouse outer medullary collecting ducts. AngII (10 nM) stimulated concanamycin-sensitive vacuolar H<sup>+</sup>-ATPase activity in A-IC in freshly isolated mouse outer medullary collecting ducts <i>via</i> AT<sub>1</sub> receptors, which were also detected immunohistochemically in A-IC. AngII increased intracellular Ca<sup>2+</sup> levels transiently. Chelation of intracellular Ca<sup>2+</sup> with BAPTA and depletion of endoplasmic reticulum Ca<sup>2+</sup> stores prevented the stimulatory effect on H<sup>+</sup>-ATPase activity. The effect of AngII on H<sup>+</sup>-ATPase activity was abolished by inhibitors of small G proteins and phospholipase C, by blockers of Ca<sup>2+</sup>-dependent and -independent isoforms of protein kinase C and extracellular signal–regulated kinase 1/2. Disruption of the microtubular network and cleavage of cellubrevin attenuated the stimulation. Finally, AngII failed to stimulate residual vacuolar H<sup>+</sup>-ATPase activity in A-IC from mice that were deficient for the B1 subunit of the vacuolar H<sup>+</sup>-ATPase. Thus, AngII presents a potent stimulus for vacuolar H<sup>+</sup>-ATPase activity in outer medullary collecting duct IC and requires trafficking of stimulatory proteins or vacuolar H<sup>+</sup>-ATPases. The B1 subunit is indispensable for the stimulation by AngII, and its importance for stimulation of vacuolar H<sup>+</sup>-ATPase activity may contribute to the inappropriate urinary acidification that is seen in patients who have distal renal tubular acidosis and mutations in this subunit.
Hidden by HIPAA: The Costs of Cure
Authors: Derek Raghavan
Journal: Journal of Clinical Oncology (2005)

In the second half of the last century, there were dramatic improvements in the management of advanced cancers of the genitourinary tract, with particular progress in the management of germ cell tumors. The management of metastatic testicular germ cell tumors has become one of the paradigms of successful cancer treatment, reflecting progress in the development of chemotherapy and an improved understanding of the principles of tumor biology, and of the importance of multidisciplinary management. Withincreasingexperience,wehavecometorecognizethat theseapproachestotreatmenthavesomeflaws,particularly with respect to the creation of late iatrogenic effects, and this has become the focus of intense scrutiny. An increased understanding of risk factors has allowed us to tailor our treatments to the level of risk, such as reducing the number of cycles of chemotherapy required for good-risk metastatic disease, based on randomized trial data. We have attempted to avoid some of the late complications of treatment by modifying some treatment approaches. However, some of these attempts to improve treatmentoutcomesbyreducingtoxicityhavefailed,largely becauseofareductionintheinitialcurerate—forexample, the attempt to avoid the nephrotoxicity of cisplatin by the
Adding chemotherapy to hormonal therapy prolongs survival in metastatic prostate cancer, study finds:
Authors: Susan Mayor
Journal: BMJ (2015)

Adding chemotherapy to androgen deprivation therapy significantly prolongs survival more than hormonal therapy alone in men with hormone sensitive metastatic prostate cancer, shows a randomised study reported in the New England Journal of Medicine .1

Androgen deprivation therapy has been the backbone of the treatment for metastatic prostate cancer since the 1940s, but most patients become resistant to this treatment over time, and the median survival is currently around three years. The potential benefit of adding chemotherapy has been unclear, but …
Possible roles of the peripheral vagal nerve in histamine-induced bronchoconstriction in guinea-pigs
Authors: H Inoue, H Aizawa, N Miyazaki, T Ikeda, N Shigematsu
Journal: European Respiratory Journal (1991)

Although the importance of the vagal nerve in the pathogenesis of bronchial asthma has been reported, its precise contribution is still not fully understood. To shed more light on this area, we evaluated the possible contribution of vagal reflex in histamine-induced bronchoconstriction (HIB), and decided the site of action of histamine on the vagal nerve. For this purpose, we studied the effects of the bilateral cervical vagotomy, hexamethonium (2 mg.kg-1) or tetrodotoxin (0.5 mg.kg-1) on HIB (8 micrograms.kg-1, iv) in anaesthetized and mechanically-ventilated guinea-pigs. We also studied whether or not atropine (1 mg.kg-1) decreases HIB after vagotomy, including either the treatment of hexamethonium or tetrodotoxin. Airway responses were assessed by measurement of pulmonary resistance. The following results were obtained; 1) the response to histamine was significantly enhanced by the vagotomy, hexamethonium or tetrodotoxin; 2) propranolol increased HIB, and HIB was further enhanced by the vagotomy in the animals treated with propranolol; 3) atropine significantly suppressed HIB after the vagotomy, hexamethonium or tetrodotoxin. These results suggest that the postganglionic vagal nerve plays an excitatory role in HIB through the release of acetylcholine from the nerve terminals. It is also suggested that the vagal reflex mainly exhibits an inhibitory role in the HIB of guinea-pigs, presumably by the action of the nonadrenergic inhibitory nervous system.
Preliminary evidence for involvement of the tumour suppressor gene CHD5 in a family with cutaneous melanoma
Authors: J. Lang, E.S. Tobias, R. MacKie
Journal: British Journal of Dermatology (2011)

Journal Article Preliminary evidence for involvement of the tumour suppressor gene CHD5 in a family with cutaneous melanoma Get access J. Lang, J. Lang Medical Genetics, Duncan Guthrie Institute, University of Glasgow, Yorkhill Hospitals, Glasgow, U.K. Julie Lang. E‐mail: J.Lang@clinmed.gla.ac.uk Search for other works by this author on: Oxford Academic Google Scholar E.S. Tobias, E.S. Tobias Medical Genetics, Duncan Guthrie Institute, University of Glasgow, Yorkhill Hospitals, Glasgow, U.K. Search for other works by this author on: Oxford Academic Google Scholar R. MacKie R. MacKie Department of Public Health and Health Policy, Glasgow University, Glasgow, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 164, Issue 5, 1 May 2011, Pages 1010–1016, https://doi.org/10.1111/j.1365-2133.2011.10223.x Published: 01 May 2011
High Frequency of Functionally Active Melan-A–Specific T Cells in a Patient with Progressive Immunoproteasome-Deficient Melanoma
Authors: Norbert Meidenbauer, Alfred Zippelius, Mikaël J. Pittet, Monika Laumer, Sandra Vogl, Jana Heymann, Michael Rehli, Barbara Seliger, Stephan Schwarz, Frederique-Anne Le Gal, Pierre Y. Dietrich, Reinhard Andreesen, Pedro Romero, Andreas Mackensen
Journal: Cancer Research (2004)

Abstract Tumor-reactive T cells play an important role in cancer immunosurveillance. Applying the multimer technology, we report here an unexpected high frequency of Melan-A–specific CTLs in a melanoma patient with progressive lymph node metastases, consisting of 18 and 12.8% of total peripheral blood and tumor-infiltrating CD8+ T cells, respectively. Melan-A–specific CTLs revealed a high cytolytic activity against allogeneic Melan-A–expressing target cells but failed to kill the autologous tumor cells. Loading of the tumor cells with Melan-A peptide reversed the resistance to killing, suggesting impaired function of the MHC class I antigen processing and presentation pathway. Mutations of the coding region of the HLA-A2 binding Melan-A26–35 peptide or down-regulation of the MHC class I heavy chain, the antigenic peptide TAP, and tapasin could be excluded. However, PCR and immunohistochemical analysis revealed a deficiency of the immunoproteasomes low molecular weight protein 2 and low molecular weight protein 7 in the primary tumor cells, which affects the quantity and quality of generated T-cell epitopes and might explain the resistance to killing. This is supported by our data, demonstrating that the resistance to killing can be partially reversed by pre-exposure of the tumor cells to IFN-γ, which is known to induce the immunoproteasomes. Overall, this is the first report of an extremely high frequency of tumor-specific CTLs that exhibit competent T-cell–effector functions but fail to lyse the autologous tumor cells. Immunotherapeutic approaches should not only focus on the induction of a robust antitumor immune response, but should also have to target tumor immune escape mechanisms.