Does the beta-blocker nebivolol increase coronary flow reserve?

INTRODUCTION: Nebivolol, a highly selective beta1-adrenergic receptor-blocker, increases basal and stimulated endothelial nitric oxide (NO)-release. It is unknown, whether coronary perfusion is improved by the increase in NO availability. Therefore, we sought to evaluate the effect of nebivolol on coronary flow reserve (CFR) and collateral flow. METHODS: Doppler-flow wire derived coronary flow velocity measurements were obtained in ten controls and eight patients with coronary artery disease (CAD) at rest and after intracoronary nebivolol. CFR was defined as maximal flow during adenosine-induced hyperemia divided by resting flow. In the CAD group, collateral flow was determined after dilatation of a flow-limiting coronary stenosis. Collateral flow index (CFI) was defined as the ratio of flow velocity during balloon inflation divided by resting flow. RESULTS: CFR at rest was 3.0+/-0.6 in controls and 2.1+/-0.4 in CAD patients. After intracoronary doses of 0.1, 0.25, and 0.5 mg nebivolol, CFR increased to 3.4+/-0.7, 3.9+/-0.9, and 4.0+/-0.1 (p<0.01) in controls, and to 2.3+/-0.7, 2.6+/-0.9, and 2.6+/-0.5 (p<0.05) in CAD patients. CFI decreased significantly with intracoronary nebivolol and correlated to changes in heart rate (r=0.75, p<0.001) and rate-pressure product (r=0.59, p=0.001). DISCUSSION: Intracoronary nebivolol is associated with a significant increase in CFR due to reduction in resting flow (controls), or due to an increase in maximal coronary flow (CAD patients). CFI decreased with nebivolol parallel to the reduction in myocardial oxygen consumption.

Management of infusion reactions in clinical trials and beyond: the US and EU perspectives

Monoclonal antibodies have expanded our cancer-fighting armamentarium in both the United States and Europe. While in general, monoclonal antibodies are well tolerated and do not have significant overlapping side effects with traditional cytotoxic agents, severe infusion reactions (IRs)--sometimes severe enough to be life threatening--have been reported. The pathophysiology of severe infusion reactions associated with monoclonal antibodies is poorly understood, but mechanisms are beginning to be elucidated. Geographic differences in the incidence of IRs have become apparent. Understanding the risk, recognizing the signs and symptoms, and being ready to promptly manage severe IRs are key for the clinician to avoid unnecessarily discontinuing these effective anticancer agents and prevent potentially tragic consequences for their patients. To date, clinical trials have incorporated monoclonal antibodies into combinations with standard cytotoxic regimens; it is expected that in time clinical trials will be testing promising new combinations utilizing multiple targeted agents, resulting in improved toxicity profiles and efficacy for cancer patients.

A discourse-theoretic approach to negotiated rulemaking

In 1996 and in 1997, Congress ordered the Secretary of Health and Human Services to undertake a process of negotiated rulemaking, which is authorized under the Negotiated Rulemaking Act of 1990, on three separate rulemaking matters. Other Federal agencies, including the Environmental Protection Agency and the Occupational Health and Safety Administration, have also made use of this procedure. As part of the program to reinvent government, President Clinton has issued an executive order requiring federal agencies to engage in some negotiated rulemaking procedures. I present an analytic, interpretative and critical approach to looking at the statutory and regulatory provisions for negotiated rulemaking as related to issues of democratic governance surrounding the problem of delegation of legislative power. The paradigm of law delineated by Jürgen Habermas, which sets law the task of achieving social or value integration as well as integration of systems, provides the background theory for a critique of such processes. My research questions are two. First, why should a citizen obey a regulation which is the result of negotiation by directly interested parties? Second, what is the potential effect of negotiated rulemaking on other institutions for deliberative democracy? For the internal critique I argue that the procedures for negotiated rulemaking will not produce among the participants the agreement and cooperation which is the legislative intent. For the external critique I argue that negotiated rulemaking will not result in democratically-legitimated regulation. In addition, the practice of negotiated rulemaking will further weaken the functioning of the public sphere, as Habermas theorizes it, as the central institution of deliberative democracy. The primary implication is the need to mitigate further development of administrative agencies as isolated, self-regulating systems, which have been loosened from the controls of democratic governance, through the development of a robust public sphere in which affected persons may achieve mutual understanding. ^

Paths to Power: The Ascendance of Contemporary Democratic Congressional Leaders

Congressional leadership is a constantly changing phenomenon. New factors and actors are constantly affecting and altering which members ascend to positions of leadership and how that leadership is exercised. A critical change that has occurred in recent times is the inclusion of women in the congressional leadership for the first time. While there has been a great deal of theoretical work on gender and on congressional leadership, there have not been enough actual female leaders in Congress to perform a study until now. The present study examines the impact of gender, committee/legislative performance, ideology, and fundraising ability on leadership ascendancy. The variables are investigated through a comparative case study of Rep. Nancy Pelosi, Rep. Rosa DeLauro, Sen. Hillary Clinton and Sen. Harry Reid.

Preßprozeß Sebastian Brunner contra Ignaz Kuranda : verhandelt am 10. Mai vor dem Wiener Landesgericht in Strafsachen

Leopold Conn

Na 1 Nachlass Max Horkheimer, 682 - "Antisemitism among American Labor" (p. IX 146.2-4 - IX 146.5-23)

"Antisemitism and American Labor. A Research Project of the Institut of Social Research", Januar 1944 (revised June 1944); a) als Typoskript vervielfältigt, 14 Blatt; b) Typoskript, 14 Blatt; Institut of Social Research: "Project an Antisemitism and American Labor", Januar 1944; a) Typoskript, 18 Blatt; b) Typoskript, mit handschriftlichen Korrekturen, 17 Blatt, c) Teilstück, Typoskript mit handschriftlichen Korrekturen, 1 Blatt; d) Teilstück, Typoskript mit handschriftlichen Korrekturen, 1 Blatt; e) Teilstück, Typoskript mit handschriftlichen Korrekturen, 5 Blatt; f) Teilstück, Typoskript mit handschriftlichen Korrekturen, 4 Blatt; "Project on Antisemitism an American Labor", Dezember 1943; a) Typoskript mit handschriftlichen Korrekturen, 18 Blatt; b) Typoskript mit handschriftlichen Korrekturen von Theodor W. Adorno, 17 Blatt; c) Typoskript mit handschriftlichen Korrekturen, 12 Blatt; Memoranden 1941-1949; Adorno, Theodor W. to Löwenthal, Leo: "Supplement to the Memorandum of 7/28/49 by Pollock, Friedrich re Labor Study", 18.09.1949. Typoskript, 6 Blatt; Adorno, Theodor W.: "Memorandum re: Antisemitism among American Labor, as edited by the Bureau of Applied Social Research", 19.07.1949. Typoskript, 8 Blatt; "Expenses for Project: Antisemitism among Labor, june 1, 1944- May 31,1945". Typoskript, 1 Blatt; Institut of Social Research: "Interim Memorandum on Progress of Project on Antisemitism within Labor", 04.09.1944. Typoskript, 11 Blatt; Institut of Social Research: "Re: Project on Labor and Antisemitism. Difficulties to be expected", 21.03.1944. Typoskript, 3 Blatt; "Re: Project on Labor and Antisemitism. Plants to be Contacted", 21.03.1944. Typoskript, 2 Blatt; "Some Remarks to Dr. Gelle's Report 'Der deutsche Progrom, a, 10. November 1938'", 11.03.1944. Typoskript, 12 Blatt; Adorno, Theodor W. ?: "Adress to ameeting of the Jewish Labor Committee, January 20th, 1944, los Angeles". Typoskript mit eigenhändigen Ergänzungen, 2 Blatt; Pollock, Friedrich: "Re: Sherman", 31.12.1943, 1 Blatt; "Memorandum re: Jewish Labor Committee", 23.12.1943. Typoskript mit handschriftlichen Korrekturen, 2 Blatt; "Tentative Budget for a Trial Survey on Antisemitism among American Labor", 23.12.1943. Typoskript, 1 Blatt; "Council for Democracy. Survey on Antisemitism. Hartford, Conn., late 1941". Typoskript, 4 Blatt; "Council for Democracy. Survey on Antisemitism. Terre Haute, Ind.". Typoskript, 2 Blatt; Horkheimer, Max: Eigenhändige Notizen zum Projekt, 3 Blatt; "Some heading lind", handschriftlichen Notizen, 1 Blatt; Institut of Social research: "Instructuins", Fragebogen, als Typoskript vervielfältigt, 3 Blatt; "Instructions for Interviews on Attitudes of Workers and White Collar Workers towards Jews". Als Typoskript vervielfältigt, 1 Blatt; Horkheimer, Max: 1 Briefentwurf an Friedrich Pollock, ohne Ort, ohne Datum, 1 Blatt; Pollock, Friedrich: 3 Briefe an Max Horkheimer, ohne Ort, 1943, 3 Blatt; Sherman, Charles B.: 1 Brief mit Unterschrift an Friedrich Pollock, New York, 23.12.1943; 3 Briefe von Friedrich Pollock, New York, 1943-1944, 5 Blatt;

Ms. lat. oct. 286 - Vita Mariae Stuartae

Vorbesitzer: Karl Konstanz Victor Rücker;

DNA vaccination against the novel tumor antigen, MUC18, for the therapy of metastatic melanoma

Melanoma patients with metastases have a very low survival rate and limited treatment options. Therefore, the targeting of melanoma cells when they begin to invade and metastasize would be beneficial. A specific adhesion molecule that is upregulated at the vertical growth phase is the melanoma cell adhesion molecule (MCAM/MUC18). MUC18 is expressed in late primary and metastatic melanoma with little or no expression on normal melanocytes. MUC18 has been demonstrated to have a role in the progression and metastasis of human melanoma. We utilized the alphavirus-based DNA plasmid, SINCp, encoding full length human MUC18 for vaccination against B16F10 murine melanoma cells expressing human MUC18. The alphavirus-based DNA plasmid leads to the expression of large quantities of heterologous protein as well as danger signals due to dsRNA intermediates produced during viral replication. In a preventative primary tumor model and an experimental tumor model, mice vaccinated against human MUC18 had decreased tumor incidence and reduced lung metastases when challenged with B16F10 murine melanoma cells expressing human MUC18. In a therapeutic tumor model, vaccination against human MUC18 reduced the tumor burden in mice with pre-existing lung metastases but did not have a significant effect on therapeutic vaccination in a primary tumor model. We next cloned murine MUC18 into SINCp for use in determining the efficacy of vaccination against murine MUC18 in a syngeneic animal model. Mice were vaccinated and challenged in a primary tumor and experimental metastasis model. In both models, vaccination significantly reduced tumor incidence and lung metastases. Humoral and cell-mediated responses were then determined. Flow cytometry and immunohistochemistry showed that specific antibodies were developed from vaccination against both human and murine MUC18. IgG2a antibody isotype was also developed indicating a Th1 type response. ELISPOT results showed that mice vaccinated against human MUC18 created a specific T cell response to targets expressing human MUC18. Mice vaccinated against murine MUC18 raised specific effector cells against target cells expressing murine MUC18 in a cell killing assay. These results indicate that vaccination against MUC18 developed specific immune responses against MUC18 and were effective in controlling tumor growth in melanoma expressing MUC18. ^