1,548 research outputs found
The coxibs, selective inhibitors of cyclooxygenase-2
No full textDrug TherapyALASTAIR J.J. WOOD, M.D., EditorDRUG THERAPYN Engl J Med, Vol. 345, No. 6·August 9, 2001·www.nejm.org·433THE COXIBS, SELECTIVE INHIBITORSOF CYCLOOXYGENASE-2GARRET A. FITZGERALD, M.D., AND CARLO PATRONO, M.D.From the Center for Experimental Therapeutics, University of Pennsyl-vania, Philadelphia (G.A.F.); and the Department of Medicine and Centerof Excellence on Aging, University of Chieti, Chieti, Italy (C.P.). Addressreprint requests to Dr. FitzGerald at the Department of Pharmacology, 153Johnson Pavilion, 3620 Hamilton Walk, University of Pennsylvania, Phila-delphia, PA 19104-6084, or at [email protected] antiinflammatory drugs(NSAIDs) are widely used to treat arthritis,menstrual pain, and headache. Although theyare effective, their long-term use is limited by gas-trointestinal effects such as dyspepsia and abdominalpain and, less often, gastric or duodenal perforationor bleeding. Development of the coxibs, a new groupof antiinflammatory drugs, represents a response tothe unsatisfactory therapeutic profile of NSAIDs. Bothgroups of drugs inhibit prostaglandin G/H synthase,the enzyme that catalyzes the transformation of arach-idonic acid to a range of lipid mediators, termedprostaglandins and thromboxanes (Fig. 1). However,whereas NSAIDs inhibit the two recognized forms ofthe enzyme, also referred to as cyclooxygenase-1 andcyclooxygenase-2, the coxibs are selective inhibitorsof cyclooxygenase-2. The inhibition of cyclooxygen-ase-2 has been more directly implicated in ameliorat-ing inflammation, whereas the inhibition of cycloox-ygenase-1 has been related to adverse effects in thegastrointestinal tract. Therefore, it was hoped thatcoxibs would be better tolerated than nonselectiveNSAIDs but equally efficacious. This review will as-sess the evidence that has emerged in suppor
«L'Évolution de la politique extérieure de l'Irlande, 1922-1986»
No full textDr Garret FitzGerald, Ireland's Prime Minister, stresses the amazing continuity of Irish foreign policy since the emergence of the new independent Irish State in 1922 in spite of the fierce ideological antagonism between the Cosgrave administration and the Government led by Eamon de Valera after 1932. By different means, in a different set of circumstances, they were both de dicated to the fulfillment of total sovereignty to the detriment of the reunification of the island divided in 1920. The same unity of vision gave shape to the foreign policy of the country as far as neutrality, the attitude towards the Third World, economic independence and the role of Ireland in the EEC were concerned.Le Dr Garret FitzGerald, Premier Ministre de la République d'Irlande, met en relief la surprenante continuité de la politique étrangère irlandaise depuis l'indépendance, alors même que la politique intérieure était caractérisée par le choc des antagonismes idéologiques hérités de la guerre civile. Par des voies différentes, en des circonstances dissemblables, il montre que les gouvernements Cosgrave et de Valera furent l'un et l'autre soucieux avant tout de parachever l'indépendance politique du nouvel Etat au détriment de la réunification de l'île divisée depuis 1920. La même unité de vues se fait jour dans des domaines aussi variés que la neutralité, l'aide au Tiers Monde, l'indépendance économique et le rôle de l'Irlande au sein de la Communauté Européenne.Fitzgerald Garret. «L'Évolution de la politique extérieure de l'Irlande, 1922-1986». In: Études irlandaises, n°11, 1986. pp. 113-126
De Valera and Contemporary Ireland
No full textBeing the leader of Fine Gael as well as Taoiseach of an anti-Fianna Fail government coalition, Dr Garret Fitzgerald does not pretend to write about de Valera as a dispassionate academic historian. Nevertheless he endeavours to be as objective as possible in reviewing the five main challenges that faced the Irish Statesman : the legitimacy of the new State and the consensus of the people of Ireland ; the right to remain neutral and the assertion of that right during the second world war ; the Northern Ireland question ; the definition of the identity of the new Irish State as a pluralist or a mono-cultural State ; the treatment of economic and social questions. On the credit side, de Valera secured the sovereignty and legitimisation of the State and added to his country's stature in the world. On the debit side, he failed to make progress with the political reunification of the island. In the economic sphere, he sought self-sufficiency through industrialisation, and achieved industrialisation with a reduction in self-sufficiency. In the social sphere, he was a natural conservative : his dream of «a people satisfied with frugal comfort» has ceased to be relevant in contemporary Ireland. He was a great Statesman of the calibre of O'Connell and Parnell with no less virtues and defects than his illustrious predecessors.En tant que leader du Fine Gael et Premier Ministre d'un gouvernement de coalition anti-Fianna Fail, le Dr Garret Fitzgerald ne prétend pas écrire sur de Valera en historien détaché. Néanmoins, il s'efforce d'être aussi objectif que possible dans l'exposé des cinq principaux défis que l'homme d'Etat irlandais fut contraint de relever : la légitimité du nouvel État et le concensus du peuple irlandais ; le droit de rester neutre et l'exercice de ce droit pendant la seconde guerre mondiale ; la question nord-irlandaise ; la définition de l'identité du nouvel État irlandais en tant qu'Etat pluraliste ou État mono-culturel ; les réponses apportées aux questions économiques et sociales. Au crédit, de Valera a affermi la souveraineté et la légitimité de l'État en même temps qu'il rehaussait le prestige de son pays dans le monde. Au débit, il échoua dans sa tentative d'aboutir à la réunification politique de l'Irlande. Dans la sphère économique, il rechercha l'auto -suffisance par l'industrialisation et obtint l'industrialisation par la réduction de l'auto-suffisance. Dans le domaine social, il fut un conservateur-né : son rêve d'un «peuple vivant heureux dans un confort frugal» n'est plus en rapport avec l'Irlande contemporaine. Il fut un grand homme d'État, de la stature d'O'Connell et Parnell, montrant les mêmes qualités et insuffisances que ses illustres prédécesseurs.Fitzgerald Garret. De Valera and Contemporary Ireland. In: Études irlandaises, n°9, 1984. pp. 229-248
A Relational Theory of Authorship
No full textOver the years we have heard the debate as to whether authorship emanates solely from the individual or from the cultural context in which they inhabit. Writers such as Professors Woodmansee, Jaszi and Cohen have asserted a cultural theory of authorship. On one hand, there is the liberal philosophy of autonomous creativity evidenced in the notion of a "romantic author" (after the period known as romanticism). On the other hand we have more of a communitarian notion – that the author acts in a cultural context and authorship to some extent must be linked back to the social existence within which the author is situated.\ud
\ud
This article argues that for too long we have privileged the notion of the romantic author so much so that it is hard to argue for any other approach to copyright than one that focuses primarily on the author and their assignees such as publishers or associated commercialising agents such as recording companies. Furthermore it suggests that this approach fits awkwardly with the burgeoning networked society fuelled by the Internet to the point where it threatens innovation and the potential for productivity. To this end the article argues that we should more explicitly acknowledge the contribution of culture to authorship and more so the role of each and every individual in assisting and nurturing that authorship, as well as the contribution of users to creativity through consumptive, productive and transformative use of copyright works
Angioplasty increases coronary sinus F-2-isoprostane formation: Evidence for in vivo oxidative stress during PTCA
No full textOBJECTIVES soprostanes, stable end-products of oxygen free radical mediated-lipid peroxidation, were measured in the coronary vessels during percutaneous transluminal coronary angioplasty (PTCA) to provide direct evidence for enhanced oxidative stress in a local milieu in vivo. BACKGROUND Percutaneous transluminal coronary angioplasty is associated with complications such as myocardial stunning and accelerated restenosis, which at least in part are mediated by oxygen free radicals. Because isoprostanes are markers of oxidant stress and potent vasoactive compounds, the formation of which is not inhibited by aspirin treatment in vivo, it is possible that these mediators are increased locally during PTCA. METHODS In 12 coronary artery disease patients who were given aspirin and ticlopidine, blood samples from coronary sinus were taken immediately before and immediately upon balloon deflation during PTCA. Isoprostane F-2 alpha-III, isoprostane F-2 alpha-VI, and TxB(2) were quantified after extraction and chromatography using a stable dilution isotope gas chromatography/mass spectrometry assay. RESULTS Coronary sinus and left main coronary artery levels of iPF(2 alpha)-III and IPF2 alpha-VI at baseline were (mean +/- SEM) 40 +/- 9 pg/ml and 115 +/- 10 pg/ml, respectively. The TxB(2) levels were undetectable. Following PTCA, isoprostane levels markedly increased (mean +/- SEM): IPF2 alpha-III, 125 +/- 12 pg/ml (p < 0.001); iPF(2)-VI, 295 +/- 20 pg/ml (p < 0.001), whereas TxB(2) levels remained undetectable. CONCLUSIONS These results indicate that PTCA induces coronary sinus increase in F-2-isoprostane formation, and they also provide direct evidence for enhanced oxidative stress in a local milieu in vivo. Thus, an increased F-2-isoprostane formation could play a role in the pathogenesis of some PTCA-associated untoward events. (J Am Cell Cardiol 2001;37:76-80) (C) 2001 by the American College of Cardiology
Book review: Garret Fitzgerald: all in a life: an autobiography / by Michael Gallagher. Dublin: Gill and Macmillan, 1991.
No full text
Urinary Prostaglandin Metabolites
No full textGrosser T, Naji A, FitzGerald GA. Urinary Prostaglandin Metabolites. Circulation Research. 2018;122(4):537-539
Ongoing prothrombotic state in patients with antiphospholipid antibodies: A role for increased lipid peroxidation
No full textWe measured the urinary excretion of Isoprostane F2alpha-III and Isoprostane-F2alpha-VI, two markers of in vivo lipid peroxidation, and the circulating levels of the prothrombin fragment F1+2, a marker of thrombin generation, in 18 antiphospholipid antibodies-positive patients, in 18 antiphospholipid antibodies-negative patients with systemic lupus erythematosus, and in 20 healthy subjects. Furthermore, 12 patients positive for antiphospholipid antibodies were treated with (n = 7) or without (n = 5) antioxidant vitamins (vitamin E at 900 IU/d and vitamin C at 2, 000 mg/d) for 4 weeks. Compared with antiphospholipid antibodies-negative patients, antiphospholipid antibodies-positive patients had higher urinary values of Isoprostane-F2alpha-III (P =. 0001), Isoprostane-F2alpha-VI (P =.006), and plasma levels of the prothrombin fragment F1+2 (P =.0001). In antiphospholipid-positive patients, F1+2 significantly correlated with Isoprostane-F2alpha-III (Rho =.56, P =.017) and Isoprostane-F2alpha-VI (Rho =.61, P =.008). After 4 weeks of supplementation with antioxidant vitamins, we found a significant decrease in F1+2 levels (P <.005) concomitantly with a significant reduction of both Isoprostane-F2alpha-III (P =.007) and Isoprostane-F2alpha-VI (P <.005). No change of these variables was observed in patients not receiving antioxidant treatment. This study suggests that lipid peroxidation might contribute to the activation of clotting system in patients positive for antiphospholipid antibodies
Fitzgerald, Ella, circa 1940
No full textPortrait of Ella Fitzgerald. Written on recto: To my big "brudda," May the very, very [?] of success, health and happiness be found. Straight from my heart [?] Sincerely [?] Ella [?]
- …
