CATEGORY A – PLACE Category A Place

CATEGORY A – PLACE Category A Place tài liệu, giáo án, bài giảng , luận văn, luận án, đồ án, bài tập lớn về tất cả các l...

BioMed Central Page 1 of 5 (page number not for citation purposes) AIDS Research and Therapy Open Access Short report A placebo-controlled pilot study of intensification of antiretroviral therapy with mycophenolate mofetil Rupinderjeet Kaur 1 , Roger Bedimo 1,3 , Mary Beth Kvanli 3 , Diana Turner 3 , Leslie Shaw 2 and David Margolis* 1,3 Address: 1 University of Texas Southwestern Medical Center at Dallas, Department of Medicine, Division of Infectious Diseases, Dallas, TX 75390, USA, 2 University of Pennsylvania, Philadelphia, PA 19104, USA and 3 North Texas Veterans Health Care Systems, Dallas, TX 75216, USA Email: Rupinderjeet Kaur - rupindervirk@hotmail.com; Roger Bedimo - roger.bedimo@med.va.gov; Mary Beth Kvanli - mary.kvanli@med.va.gov; Diana Turner - diana.turner@med.va.gov; Leslie Shaw - shawlmj@mail.med.upenn.edu; David Margolis* - dmargo@med.unc.edu * Corresponding author Abstract Purpose: We studied the safety, tolerability, virologic, and immunologic effects of mycophenolate mofetil (MMF) added to a stable antiretroviral therapy (ART) in the setting of low-level viremia. Methods: MMF 500 mg BID or placebo was given to patients thought to be adherent on stable ART with plasma viremia between 200 and 4000 copies/mL. At week 4 unblinding was performed and patients on placebo were offered open-label MMF. Results: Six patients were enrolled. At entry mean plasma HIV-1 RNA (VL) was 2.98 log 10 copies/ mL; mean CD4 count was 523. All subjects randomized to placebo elected to cross over to open label MMF. No significant adverse events were observed during MMF therapy. Three patients on MMF achieved VL < 50 copies/mL by week 4; a fourth had VL decline of > 0.5 log. Two patients on placebo had declines of VL. One of these had further decline on open label MMF. Cell surface markers of apoptosis, activation, and proliferation on CD4+ and CD8+ cells declined modestly or remained low. CD4 counts were stable at week 24. All but one subject had rebound of viremia by week 24, universally associated with missed doses of medication by pill count. Conclusion: MMF appears to be safe, and its administration lead to decreased T cell activation. During periods of adherence to therapy, the use of MMF was correlated with declines in viremia, but this small pilot study could not prove this association. Further study of MMF in patients with viremia should be considered for whom additional or alternative antiretrovirals are impractical. Introduction The adjunctive use of inhibitors of nucleoside metabolism may exploit the reliance of HIV-1 on nucleoside pools for reverse transcription. Further, directly blunting host cell activation might have clinical benefits in HIV infection. Mycophenolic acid (MPA) is a selective and reversible inhibitor of de novo synthesis of deoxyguanosine triphos- phate (dGTP) [1,2]. MPA's effects are selective for lym- phocytes, and it suppresses HIV replication through guanine depletion [3], increasing the efficacy of several Published: 26 May 2006 AIDS Research and Therapy 2006, 3:16 doi:10.1186/1742-6405-3-16 Received: 28 February 2006 Accepted: 26 May 2006 This article is available from: http://www.aidsrestherapy.com/content/3/1/16 © 2006 Kaur et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. AIDS Research and Therapy 2006, 3:16 http://www.aidsrestherapy.com/content/3/1/16 Page 2 of 5 (page number not for citation purposes) reverse transcriptase inhibitors in vitro [4-6] and in vivo [7-10]. We hypothesized that MMF could improve virologic sup- pression in the setting of low-level viremia, preserving other antiretroviral agents for future use. We conducted a placebo-controlled pilot study to evaluate the safety, tol- erability, and PART CATEGORY A: PLACE A restaurant you like (to go to) / that impress you Let me tell you about a cheap restaurant I often go to It’s located next to the training school where I have been studying English for the last two months It only takes me five minutes to get there In fact, it’s a tiny restaurant with several tables inside When the weather is good, clients love to eat outside to enjoy the fresh air I frequently go to this restaurant with my classmates because the food is very tasty, and the prices are extremely reasonable They offer typical Vietnam food with a great choice of dishes: local specialties such as sweet and sour pork, as well as fish balls served in soup But I can also get spicy food, like spicy diced chicken with peanuts, or simple spicy green beans In addition, the boss is a friendly old man, and the waitresses remember their customers and even what they like to eat They often give us a small discount when we ask for the bill: they know how to retain their clients What’s the most important is that the food is clean, savoury and cheap That’s what really counts A place you went to That was Full of color The Colourful place I once went to was a kindergarten I went to my aunt's home in another city for my vacation last year One day, my aunt was too busy to pick up my niece from the kindergarten, so I went there in place of her It was my first time to visit that kindergarten I was shocked by the colourful wall when I stepped into their classroom Kids in this kindergarten could paint the picture directly on the wall using various crayons Then I asked the teacher why they allowed the kids to so The teacher told me that creating a colourful world was essential for children They felt free to draw their imagined world whenever they wanted Other kindergartens might not allow the kids to so, but the teacher in this kindergarten thought that forbidding children to something creative was not a wise choice and it would ruin children's creativity and imagination Besides, the classroom is also decorated with other colourful things such as green chairs, yellow desks, which is helpful to cultivate children's colour sensibility Teachers in this kindergarten even draw the colourful pictures together with the kids, which creating a harmonious atmosphere in the kindergarten If I had a child, I would definitely decorate his / her room with colourful things and allow her / him to draw on the wall 1 Describe an unusual building you’ve visited An unusual building that I have seen is the Bird's Nest, a national stadium which is situated in Olympic Green Village, Chaoyang District in Beijing It was designed as the main stadium of 2008 Beijing Olympic Games The Olympic events of track and field, football , gavelock, weight throw and discus were held there Since October, 2008, after the Olympics ended, it has been opened as a tourist attraction Now, it's the center of some international or domestic sports competitions and recreation activities It is saddle- shaped, but the interlocking steel parts resembling a lattice of twigs, which makes the stadium look like a bird's nest I remember when I first saw this stadium, I soon attracted by its appearance It seems that it's a real bird's nest in a larger size I've never seen a stadium like this When I entered into the stadium, I felt that I was lying in a large bird's nest and it would protect me from being hurt by the outside world The Bird's Nest stadium completely changed my understanding about the traditional stadiums I think its designer must be full of imagination This is probably the most unusual and modern stadium I have ever seen Describe a place near water that you enjoyed visiting Well, if you let me talk about a place near water, the memory of childhood trip experience which was when I was about five years old came out of my mind At that time, my father took me back to his hometown for a visit and we stayed there for quite a few days What impressed me most was the reservoir we visited It was the first time that I saw and knew what a reservoir was As my dad told me, the reservoir storage enough water for the whole local village to use in emergency Also my day told me the reservoir benefited the village a lot For instance, sometimes the village might be lack of irrigation because of harsh climate conditions As a source of water, the reservoir played a significant role in facilitating villagers in respect of agriculture Also local people used the reservoir for fish-culture During the period I stayed there, I learned how to fish with the assistant of my dad and some local villagers They told me how to cast my fishing line into the lake I regarded the fishing as a leisure activity because I can relax myself and enjoy excitement thoroughly 2 It was such an unforgettable and precious memory for me to visit there I think if I have a chance, I would like to go there again Describe a place that can be good to relax (not home) Well, your questions have reminded me of the ...RESEARC H Open Access Indacaterol provides 24-hour bronchodilation in COPD: a placebo-controlled blinded comparison with tiotropium Claus Vogelmeier 1 , David Ramos-Barbon 2 , Damon Jack 3 , Simon Piggott 3 , Roger Owen 3 , Mark Higgins 3 , Benjamin Kramer 4* , INTIME study investigators (INdacaterol & TIotropium: Measuring Efficacy) Abstract Background: Indacaterol is a novel, inhaled, once-daily, ultra-long-acting b 2 -agonist for the treatment of chronic obstructive pulmonary disease (COPD). This randomized, double-blind study compared the bronchodilator efficacy of indacaterol with that of placebo and tiotropium in patients with moderate-to-severe COPD. Methods: In an incomplete-block, multi-dose, three-period, crossover design, patients received three of the following four treatments: indacaterol 150 μg, indacaterol 300 μg, tiotropium 18 μg and pl acebo, each once-daily for 14 days. Each treatment period was separated by a 14-day washout. Study drug was supplied daily by blinded, third party study personnel to maintain blinding of patients and investigators. The primary efficacy variable was trough forced expiratory volume in one second (FEV 1 ) at 24 h post-dose after 14 da ys. The study was powered to demonstrate non-inferiority of indacaterol to tiotropium for this variabl e. Results: A total of 169 patients were randomized (mean age 65 years); 153 (90.5%) completed. Trough FEV 1 after 14 days with indacaterol 150 μg and 300 μg was statistically and clinically superior to placebo, with differences (95% CI) of 170 (120-220) and 150 (100-200) mL respectively (both p < 0.001). For this endpoint, both doses of indacaterol not only met the criterion for non-inferiority compared with tiotropium, but also achieved numerically higher values, with differences versus tiotropium of 40 and 30 mL for indacaterol 150 and 300 μg, respectively. At 5 min post-dose on Day 1, the mean FEV 1 for both indacaterol doses was significantly higher than placebo (by 120 and 130 mL for indac aterol 150 and 300 μg, respectively; p < 0.001) and tiotropium (by 80 mL for both doses; p < 0.001). Adverse events were reported by similar proportions of patients: 31.4%, 29.5%, 28.3% and 28.5% for indacaterol 150 μg and 300 μg, tiotropium and placebo treatments, respectively. Conclusions: Once-daily indacaterol provided clinically and statistically significant 24-h bronchodilation. Indacaterol was at least as effective as tiotropium, with a faster onset of action (within 5 min) on the first day of dosing. Indacaterol should prove useful in patients with moderate-to-severe COPD, for whom treatment with one or more classes of long-acting bronchodilator is recommended. Trial registration: ClinicalTrials.gov: NCT00615459, EudraCT number: 2007-004071-19 Background According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD), inhaled bronchodi- lators, including b 2 -agonists and anticholinergics, are central to the symptomatic management of chronic obstructive pulmonary disease (COPD) [1]. Currently available inhaled long-acting b 2 -agonists (LABAs), such as salmeterol and formo terol, provide bronchodilation for approximately 12 h at recommended doses, and hence are administered twice daily [2,3]. Tiotropium, the only currently available long-acting anticholinergic, has a duration of action of 24 h with once-daily dos- ing, and is effective in the long-term maintenance bronchodilator treatment of COPD [4-6]. Once-daily * Correspondence: benjamin.kramer@novartis.com 4 Novartis Pharmaceuticals Inc., One Health Plaza, East Hanover, NJ 07936- 1080, USA Full list of author information is available at the end of the article Vogelmeier et al. Respiratory Research 2010, 11:135 http://respiratory-research.com/content/11/1/135 © 2010 Vogelmeie r et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommon s.org/licenses/by/ 2.0), which BioMed Central Page 1 of 7 (page number not for citation purposes) Respiratory Research Open Access Research Concomitant therapy with Cineole (Eucalyptole) reduces exacerbations in COPD: A placebo-controlled double-blind trial Heinrich Worth* 1 , Christian Schacher 1 and Uwe Dethlefsen 2 Address: 1 Hospital Fürth, University Erlangen-Nürnberg, Jakob-Henle-Str. 1, D-90766 Fürth, Germany and 2 MKL Institute of Clinical Research, Pauwelsstr. 19, D-52074 Aachen, Germany Email: Heinrich Worth* - med1@klinikum-fuerth.de; Christian Schacher - med1@klinikum-fuerth.de; Uwe Dethlefsen - mklklifo@t-online.de * Corresponding author Abstract Background: The clinical effects of mucolytics in patients with chronic obstructive pulmonary disease (COPD) are discussed controversially. Cineole is the main constituent of eucalyptus oil and mainly used in inflammatory airway diseases as a mucolytic agent. We hypothesised that its known mucolytic, bronchodilating and anti-inflammatory effects as concomitant therapy would reduce the exacerbation rate and show benefits on pulmonary function tests as well as quality of life in patients with COPD. Methods: In this double-blind, placebo-controlled multi-center-study we randomly assigned 242 patients with stable COPD to receive 200 mg of cineole or placebo 3 times daily as concomitant therapy for 6 months during winter-time. The frequency, duration and severity of exacerbations were combined as primary outcome measures for testing as multiple criteria. Secondary outcome measures included changes of lung function, respiratory symptoms and quality of life as well as the single parameters of the exacerbations. Results: Baseline demographics, lung function and standard medication of both groups were comparable. During the treatment period of 6 months the multiple criteria frequency, severity and duration of exacerbations were significantly lower in the group treated with cineole in comparison to placebo. Secondary outcome measures validated these findings. Improvement of lung function, dyspnea and quality of life as multiple criteria were statistically significant relative to placebo. Adverse events were comparable in both groups. Conclusion: Concomitant therapy with cineole reduces exacerbations as well as dyspnea and improves lung function and health status. This study further suggests cineole as an active controller of airway inflammation in COPD by intervening in the pathophysiology of airway inflammation of the mucus membrane. Trial registration: ISRCTN07600011 Introduction Chronic obstructive pulmonary disease (COPD) is con- sidered to be a multi-component disease comprising structural and functional changes inside and outside the lungs. Effective medications for COPD are available and can reduce or prevent symptoms, increase exercise capac- Published: 22 July 2009 Respiratory Research 2009, 10:69 doi:10.1186/1465-9921-10-69 Received: 8 January 2009 Accepted: 22 July 2009 This article is available from: http://respiratory-research.com/content/10/1/69 © 2009 Worth et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The cost of publication in Journal of Biomedical Science is bourne by the National Science Council, Taiwan. Respiratory Research 2009, 10:69 http://respiratory-research.com/content/10/1/69 Page 2 of 7 (page number not for citation purposes) ity, reduce the number and severity of exacerbations and improve health status. In common clinical use are bron- chodilators as β-agonists, anticholinergic drugs and meth- ylxanthines as well as glucocorticosteroids. The clinical effectiveness of these drugs has been shown in many con- trolled clinical studies [1-7]. Airway inflammation and mucociliary dysfunction in COPD patients have direct Open Access Available online http://ccforum.com/content/11/4/R73 Page 1 of 10 (page number not for citation purposes) Vol 11 No 4 Research Effects of high doses of selenium, as sodium selenite, in septic shock: a placebo-controlled, randomized, double-blind, phase II study Xavier Forceville 1 , Bruno Laviolle 2 , Djillali Annane 3 , Dominique Vitoux 4 , Gérard Bleichner 5 , Jean- Michel Korach 6 , Emmanuel Cantais 7 , Hugues Georges 8 , Jean-Louis Soubirou 9 , Alain Combes 1 and Eric Bellissant 2 1 Service de Réanimation Polyvalente, Centre Hospitalier de Meaux, Hôpital Saint Faron, 6–8 rue Saint Fiacre, 77104 Meaux, France 2 Centre d'Investigation Clinique INSERM 0203, Unité de Pharmacologie Clinique, Hôpital de Pontchaillou, CHU de Rennes et Université de Rennes 1, 2 rue Henri le Guilloux, 35033 Rennes, France 3 Service de Réanimation Médicale, Hôpital Raymond Poincaré, 104 boulevard Raymond Poincaré, 92380 Garches, France 4 Service de Biochimie A, Hôpital Saint-Louis, avenue Claude Vellefaux, 75475 Paris cedex 10, France 5 Service de Réanimation Polyvalente, Centre Hospitalier Victor Dupouy, 69 rue du Lieut-Col Prudhon, 95107 Argenteuil cedex, France 6 Service de Réanimation Polyvalente, Centre Hospitalier, 51 rue du Commandant Derrien, 51005 Châlons en Champagne cedex, France 7 Hôpital d'Instruction des Armées Sainte Anne, boulevard Sainte Anne, 83800 Toulon Naval, France 8 Centre Hospitalier Gustave Dron, 135 rue du Président Coty, 59200 Tourcoing, France 9 Hôpital d'Instruction des Armées Desgenettes, 108 boulevard Pinel, 69003 Lyon, France Corresponding author: Xavier Forceville, xforceville@invivo.edu Received: 17 Jan 2007 Revisions requested: 14 Feb 2007 Revisions received: 28 Mar 2007 Accepted: 6 Jul 2007 Published: 6 Jul 2007 Critical Care 2007, 11:R73 (doi:10.1186/cc5960) This article is online at: http://ccforum.com/content/11/4/R73 © 2007 Forceville et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Introduction Sepsis is associated with the generation of oxygen free radicals and (lacking) decreased selenium plasma concentrations. High doses of sodium selenite might reduce inflammation by a direct pro-oxidative effect and may increase antioxidant cell capacities by selenium incorporation into selenoenzymes. We investigated the effects of a continuous administration of high doses of selenium in septic shock patients. Methods A prospective, multicentre, placebo-controlled, randomized, double-blind study was performed with an intention-to-treat analysis in severe septic shock patients with documented infection. Patients received, for 10 days, selenium as sodium selenite (4,000 μg on the first day, 1,000 μg/day on the nine following days) or matching placebo using continuous intravenous infusion. The primary endpoint was the time to vasopressor therapy withdrawal. The duration of mechanical ventilation, the mortality rates in the intensive care unit, at hospital discharge, and at 7, 14, 28 and 180 days and 1 year after randomization, and adverse events were recorded. Results Sixty patients were included (placebo, n = 29; selenium, n = 31). The median time to vasopressor therapy withdrawal was 7 days in both groups (95% confidence interval = 5–8 and 6–9 in the placebo and selenium groups, respectively; log-rank, P = 0.713). The median duration of mechanical ventilation was 14 days and 19 days in the placebo and selenium groups, respectively (P = 0.762). Mortality rates did not significantly differ between groups at any time point. Rates of adverse events were similar in the two groups. Conclusion Continuous infusion of selenium as sodium selenite (4,000 μg on the first day, 1,000 μg/day on the nine following days) had no obvious Genome Biology 2007, 8:R8 comment reviews reports deposited research refereed research interactions information Open Access 2007Panelliet al.Volume 8, Issue 1, Article R8 Research Sequential gene profiling of basal cell carcinomas treated with imiquimod in a placebo-controlled study defines the requirements for tissue rejection Monica C Panelli * , Mitchell E Stashower † , Herbert B Slade ‡ , Kina Smith * , Christopher Norwood § , Andrea Abati ¶ , Patricia Fetsch ¶ , Armando Filie ¶ , Shelley-Ann Walters ‡ , Calvin Astry ‡ , Eleonora Aricó * , Yingdong Zhao ¥ , Silvia Selleri *# , Ena Wang * and Francesco M Marincola * Addresses: * Immunogenetics Section, Department of Transfusion Medicine, Clinical Center National Institutes of Health, Bethesda, MD 20892, USA. † The Clinical Skin Center of Northern Virginia, Fairfax, VA 22033, USA. ‡ 3M Pharmaceuticals, St Paul, MN 55144-1000, USA. § Department of Dermatology, National Naval Medical Center, Bethesda, MD 20889, USA. ¶ Laboratory of Pathology, National Cancer Institute, Bethesda, MD 20892, USA. ¥ Biometric Research Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD 20892, USA. # Universita' degli Studi di Milano, Department of Human Morphology, via Mangiagalli, 20133 Milan, Italy. Correspondence: Francesco M Marincola. Email: Fmarincola@mail.cc.nih.gov © 2007 Panelli et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Imiquimod response profiling<p>An analysis of basal cell carcinoma subjected to local application of imiquimod revealed that most transcripts stimulated by imiquimod involve the activation of cellular innate and adaptive immune-effector mechanisms.</p> Abstract Background: Imiquimod is a Toll-like receptor-7 agonist capable of inducing complete clearance of basal cell carcinoma (BCC) and other cutaneous malignancies. We hypothesized that the characterization of the early transcriptional events induced by imiquimod may provide insights about immunological events preceding acute tissue and/or tumor rejection. Results: We report a paired analysis of adjacent punch biopsies obtained pre- and post-treatment from 36 patients with BCC subjected to local application of imiquimod (n = 22) or vehicle cream (n = 14) in a blinded, randomized protocol. Four treatments were assessed (q12 applications for 2 or 4 days, or q24 hours for 4 or 8 days). RNA was amplified and hybridized to 17.5 K cDNA arrays. All treatment schedules similarly affected the transcriptional profile of BCC; however, the q12 × 4 days regimen, associated with highest effectiveness, induced the most changes, with 637 genes unequivocally stimulated by imiquimod. A minority of transcripts (98 genes) confirmed previous reports of interferon-α involvement. The remaining 539 genes portrayed additional immunological functions predominantly involving the activation of cellular innate and adaptive immune-effector mechanisms. Importantly, these effector signatures recapitulate previous observations of tissue rejection in the context of cancer immunotherapy, acute allograft rejection and autoimmunity. Conclusion: This study, based on a powerful and reproducible model of cancer eradication by innate immune mechanisms, provides the first insights in humans into the early transcriptional events associated with immune rejection. This model is likely representative of constant immunological pathways through which innate and adaptive immune responses combine to induce tissue destruction. Published: 15 January 2007 Genome Biology 2007, 8:R8 (doi:10.1186/gb-2007-8-1-r8) Received: 15 August 2006 Revised: 6 October 2006 Accepted: 12 January 2007 The electronic version of this article is the complete ... that originated these features are equally amazing It just makes this place twice as appealing as a fairy tale location A great way to view this incredible scenery is by taking a boat ride down... definitely say a beautiful park in United Kingdom -the Wollaton Park It is famous as a shooting place for film Batman Last year, I got a precious chance to be an exchange student in Nottingham city At... 10-minute walk away from where I live It’s always a perfect place to visit The covered walkways provide shelter so the beautiful views can be appreciated in any weather The place is very peaceful, almost