BREPOLiS Brepolis is the home of all online projects of Brepols Publishers and its partners. Corpus Christianorum Website of the Corpus Christianorum project. TV und Radio zum Mitnehmen Mit den Podcasts und Downloads des BR knnen Sie TV und HrfunkSendungen zeitversetzt auf Ihrem Computer oder MP3Player ansehen und. Finnegans Wake is a work of avantgarde comic fiction by Irish writer James Joyce. It is significant for its experimental style and reputation as one of the most. Long acting beta agonists in the management of chronic obstructive pulmonary disease current and future agents. Abstract. Chronic obstructive pulmonary disease COPD is characterized by progressive airflow limitation and debilitating symptoms. Download Tristan Isolde Online CalculatorDownload Tristan Isolde Online GamesFor patients with moderate to severe COPD, long acting bronchodilators are the mainstay of therapy as symptoms progress, guidelines recommend combining bronchodilators from different classes to improve efficacy. Inhaled long acting 2 agonists LABAs have been licensed for the treatment of COPD since the late 1. They improve lung function, symptoms of breathlessness and exercise limitation, health related quality of life, and may reduce the rate of exacerbations, although not all patients achieve clinically meaningful improvements in symptoms or health related quality of life. In addition, LABAs have an acceptable safety profile, and are not associated with an increased risk of respiratory mortality, although adverse effects such as palpitations and tremor may limit the dose that can be tolerated. Formoterol and salmeterol have 1. COPD. A LABA with a 2. LABAs, and the once daily dosing regimen could help improve compliance. It is also desirable that a new LABA should demonstrate fast onset of action, and a safety profile at least comparable to existing LABAs. A number of novel LABAs with once daily profiles are in development which may be judged against these criteria. Indacaterol, a LABA with a 2. Preliminary results from large clinical trials suggest indacaterol improves lung function compared with placebo and other long acting bronchodilators. Other LABAs with a 2. The introduction of once daily LABAs also provides the opportunity to develop combination inhalers of two or more classes of once daily long acting bronchodilators, which may be advantageous for COPD patients through simplification of treatment regimens as well as improvements in efficacy. Once daily LABAs used both alone and in combination with long acting muscarinic antagonists represent a promising advance in the treatment of COPD, and are likely to further improve outcomes for patients. Introduction. Chronic obstructive pulmonary disease COPD is a progressive disease characterized by increasing airflow limitation and respiratory symptoms, often associated with chronic comorbidities, leading to a significant burden for the patient. Specific pharmacological therapy for COPD helps to prevent and control symptoms, reduce the frequency and severity of exacerbations, improve health status and improve exercise tolerance 1 3. Inhaled bronchodilators, such as 2 agonists and muscarinic antagonists, improve lung function by altering airway smooth muscle tone but also act on peripheral airways 4. They reduce air trapping and improve emptying of the lungs, thereby reducing lung volumes, improving symptoms such as breathlessness and increasing exercise capacity 1,5. The present review focuses on the role and future of long acting 2 agonists LABAs in the management of COPD, updating previously published reviews 6. The principal action of 2 agonists is to relax airway smooth muscle by stimulating 2 adrenergic receptors. Watch Haunted Castle Cartoon Online. This increases the intracellular messenger cyclic AMP that is responsible for the control of smooth muscle tone 7. Thus, activation of the 2 adrenergic receptor results directly in bronchodilation. Muscarinic antagonists also facilitate bronchodilation but work by competing with acetylcholine for muscarinic receptors 8. By inhibiting the action of acetylcholine at receptor sites in the lung, they indirectly inhibit contraction of airway smooth muscle. Figure 17,8 illustrates the pathways by which each class of bronchodilator produces smooth muscle relaxation. Indirect and direct relaxation of smooth muscle. Muscarinic antagonists X block M3 receptors to prevent binding of acetylcholine ACh, indirectly stimulating smooth muscle relaxation via inhibition of bronchoconstriction. COPD, either alone or in combination with other bronchodilators, corticosteroids, or both. Short acting 2 agonists SABAs were the first agents of the class to become available for the treatment of COPD. LABAs with a 1. 2 hour duration of action were subsequently introduced in the late 1. SABAs which have a duration of action of only 4 6 hours 1. The currently available SABAs and LABAs are summarized in Table 11,1. SABAs and LABAs commonly used in COPDCurrent position in management guidelines. SABAs such as salbutamol albuterol, terbutaline, pirbuterol or fenoterol andor short acting muscarinic antagonists SAMAs such as ipratropium bromide or oxitropium bromide are recommended as rescue medication for all severities of COPD to relieve acute symptoms of bronchospasm. For patients with Stage II moderate or more severe COPD, regular treatment with a twice daily LABA such as formoterol or salmeterol, or a long acting muscarinic antagonist LAMA such as tiotropium, is more effective and convenient than treatment with the shorter acting agents 1. As symptoms progress, combining bronchodilators from different classes is recommended to improve efficacy. Inhaled corticosteroids may be added to bronchodilator treatment in patients with severe COPD and a history of repeated exacerbations. No one long acting bronchodilator is recommended over another in management guidelines 1, because few studies have specifically compared different LABAs 1. In addition, studies comparing LABAs with LAMAs have not been designed or powered to answer this clinical question to date, providing inconclusive results 2. The choice therefore depends on availability and the response of the individual patient 1. Inhaled therapy is preferred to oral therapy, in light of the greater risk of systemic side effects with oral beta agonists and the unfavorable safety profile of oral methylxanthines. Recently, there has been extensive research into the efficacy and safety of available twice daily LABAs, as well as the development of new long acting 2 agonists which have the potential for once daily use 6. This paper focuses on the current and future role of LABAs in COPD management. The efficacy and safety of currently available LABAs is reviewed, and their limitations considered. Articles were identified using a Pub. Med search including search terms for all currently available LABAs salmeterol, formoterol, arformoterol, 2 agonists, efficacy, safety and chronic obstructive pulmonary diseaseCOPD. This is followed by the authors views on the ideal criteria for a new LABA for COPD, and a discussion of the extent to which novel LABAs, currently being developed, may meet these criteria. Clinical efficacy. Efficacy in COPD has traditionally been assessed primarily through impact on lung function measured by spirometry. However, to adequately understand the impact of a medication, outcomes of importance to the patient including symptoms and quality of life must also be taken into account 2. The following section reviews efficacy by endpoint to assess how far salmeterol and formoterol address the need to improve lung function, symptoms, exercise endurance, quality of life and exacerbations in patients with COPD. A summary is provided in Table 21,2. Summary of clinical efficacy for currently available 2 agonists in COPDLung function. Formoterol and salmeterol have both demonstrated significant improvements in lung function 1. Improvements in pre bronchodilator forced expiratory volume in 1 second FEV1 ranged from 5. L compared with placebo 2. Bronchodilation was rapid in onset with formoterol 3. Improvements in lung function were sustained in studies of 3 months to 3 years duration when twice daily LABAs were used as maintenance therapy 2. Some studies have suggested there may be a decline in bronchodilator efficacy over time with salmeterol 5. FVC relative to placebo 8. L, p lt 0. 0. 5, but not FEV1 1. L, were observed with salmeterol 5. Richard Wagner Wikipedia. Wilhelm Richard Wagner German iat van  listen 2. May 1. 81. 3  1. February 1. German composer, theatre director, polemicist, and conductor who is primarily known for his operas or, as some of his later works were later known, music dramas. Unlike most opera composers, Wagner wrote both the libretto and the music for each of his stage works. Initially establishing his reputation as a composer of works in the romantic vein of Weber and Meyerbeer, Wagner revolutionised opera through his concept of the Gesamtkunstwerk total work of art, by which he sought to synthesise the poetic, visual, musical and dramatic arts, with music subsidiary to drama. He described this vision in a series of essays published between 1. Wagner realised these ideas most fully in the first half of the four opera cycle Der Ring des Nibelungen The Ring of the Nibelung. His compositions, particularly those of his later period, are notable for their complex textures, rich harmonies and orchestration, and the elaborate use of leitmotifsmusical phrases associated with individual characters, places, ideas, or plot elements. His advances in musical language, such as extreme chromaticism and quickly shifting tonal centres, greatly influenced the development of classical music. His Tristan und Isolde is sometimes described as marking the start of modern music. Wagner had his own opera house built, the Bayreuth Festspielhaus, which embodied many novel design features. The Ring and Parsifal were premiered here and his most important stage works continue to be performed at the annual Bayreuth Festival, run by his descendants. His thoughts on the relative contributions of music and drama in opera were to change again, and he reintroduced some traditional forms into his last few stage works, including Die Meistersinger von Nrnberg The Mastersingers of Nuremberg. Until his final years, Wagners life was characterised by political exile, turbulent love affairs, poverty and repeated flight from his creditors. His controversial writings on music, drama and politics have attracted extensive comment, notably, since the late 2. The effect of his ideas can be traced in many of the arts throughout the 2. BiographyeditEarly yearsedit. Wagners birthplace, at 3, the Brhl, Leipzig. Richard Wagner was born to an ethnic German family in Leipzig, where his family lived at No. Brhl The House of the Red and White Lions in the Jewish quarter. He was baptized at St. Thomas Church. 1 He was the ninth child of Carl Friedrich Wagner, who was a clerk in the Leipzig police service, and his wife, Johanna Rosine ne Paetz, the daughter of a baker. Wagners father Carl died of typhus six months after Richards birth. Afterwards his mother Johanna lived with Carls friend, the actor and playwright Ludwig Geyer. In August 1. Johanna and Geyer probably marriedalthough no documentation of this has been found in the Leipzig church registers. She and her family moved to Geyers residence in Dresden. Until he was fourteen, Wagner was known as Wilhelm Richard Geyer. He almost certainly thought that Geyer was his biological father. Geyers love of the theatre came to be shared by his stepson, and Wagner took part in his performances. In his autobiography Mein Leben Wagner recalled once playing the part of an angel. In late 1. Wagner was enrolled at Pastor Wetzels school at Possendorf, near Dresden, where he received some piano instruction from his Latin teacher. He struggled to play a proper scale at the keyboard and preferred playing theatre overtures by ear. Following Geyers death in 1. Richard was sent to the Kreuzschule, the boarding school of the Dresdner Kreuzchor, at the expense of Geyers brother. At the age of nine he was hugely impressed by the Gothic elements of Carl Maria von Webers opera Der Freischtz, which he saw Weber conduct. At this period Wagner entertained ambitions as a playwright. His first creative effort, listed in the Wagner Werk Verzeichnis the standard listing of Wagners works as WWV 1, was a tragedy called Leubald. Begun when he was in school in 1. Shakespeare and Goethe. Wagner was determined to set it to music, and persuaded his family to allow him music lessons. By 1. 82. 7, the family had returned to Leipzig. Wagners first lessons in harmony were taken during 1. Christian Gottlieb Mller. In January 1. 82. Beethovens 7th Symphony and then, in March, the same composers 9th Symphony both at the Gewandhaus. Beethoven became a major inspiration, and Wagner wrote a piano transcription of the 9th Symphony. He was also greatly impressed by a performance of Mozarts Requiem. Wagners early piano sonatas and his first attempts at orchestral overtures date from this period. In 1. 82. 9 he saw a performance by dramatic soprano. Wilhelmine Schrder Devrient, and she became his ideal of the fusion of drama and music in opera. In Mein Leben, Wagner wrote When I look back across my entire life I find no event to place beside this in the impression it produced on me, and claimed that the profoundly human and ecstatic performance of this incomparable artist kindled in him an almost demonic fire. In 1. 83. 1, Wagner enrolled at the Leipzig University, where he became a member of the Saxon student fraternity. He took composition lessons with the Thomaskantor. Theodor Weinlig. 1. Weinlig was so impressed with Wagners musical ability that he refused any payment for his lessons. He arranged for his pupils Piano Sonata in B flat major which was consequently dedicated to him to be published as Wagners Op. A year later, Wagner composed his Symphony in C major, a Beethovenesque work performed in Prague in 1. Leipzig Gewandhaus in 1. He then began to work on an opera, Die Hochzeit The Wedding, which he never completed. Early career and marriage 1. In 1. 83. 3, Wagners brother Albert managed to obtain for him a position as choir master at the theatre in Wrzburg. In the same year, at the age of 2. Wagner composed his first complete opera, Die Feen The Fairies. This work, which imitated the style of Weber, went unproduced until half a century later, when it was premiered in Munich shortly after the composers death in 1. Having returned to Leipzig in 1. Wagner held a brief appointment as musical director at the opera house in Magdeburg2. Das Liebesverbot The Ban on Love, based on Shakespeares Measure for Measure. This was staged at Magdeburg in 1. Wagner had fallen for one of the leading ladies at Magdeburg, the actress Christine Wilhelmine Minna Planer2. Das Liebesverbot he followed her to Knigsberg, where she helped him to get an engagement at the theatre. The two married in Tragheim Church on 2. November 1. 83. 6. In May 1. 83. 7, Minna left Wagner for another man,3. In June 1. 83. 7, Wagner moved to Riga then in the Russian Empire, where he became music director of the local opera 3. Minnas sister Amalie also a singer for the theatre, he presently resumed relations with Minna during 1. By 1. 83. 9, the couple had amassed such large debts that they fled Riga on the run from creditors. Debts would plague Wagner for most of his life. Initially they took a stormy sea passage to London,3. Wagner drew the inspiration for his opera Der fliegende Hollnder The Flying Dutchman, with a plot based on a sketch by Heinrich Heine. The Wagners settled in Paris in September 1. Wagner made a scant living by writing articles and short novelettes such as A pilgrimage to Beethoven, which sketched his growing concept of music drama, and An end in Paris, where he depicts his own miseries as a German musician in the French metropolis. He also provided arrangements of operas by other composers, largely on behalf of the Schlesinger publishing house. During this stay he completed his third and fourth operas Rienzi and Der fliegende Hollnder. Dresden 1. 84. 21. Wagner c. 1. 84. 0, by Ernest Benedikt Kietz.