This volume of new translations unites three shorter works by Arthur Schopenhauer that expand on themes from his book The World as Will and Representation. In On the Fourfold Root he takes the principle of sufficient reason, which states that nothing is without a reason why it is, and shows how it covers different forms of explanation or ground that previous philosophers have tended to confuse. Schopenhauer regarded this study, which he first wrote as his doctoral dissertation, as an essential preliminary to The World as Will. On Will in Nature examines contemporary scientific findings in search of corroboration of his thesis that processes in nature are all a species of striving towards ends; and On Vision and Colours defends an anti-Newtonian account of colour perception influenced by Goethe's famous colour theory. This is the first English edition to provide extensive editorial notes on the different published versions of these works.

The bicentenary of William Withering's now famous medical report entitled "An Account of the Foxglove and Some of its Medical Uses" has given us the occasion to analyze the state of the art. Cardiac glycosides in 1985 are considered tobe the basis for medical treatment of myocardial failure, together with diuretics and vasodilators in the more severe cases. Nevertheless, the controversy as to their exact place in the treatment of heart failure with sinus rhythm has never ceased. Although cardiac glycosides are of unquestionable value in tachycardia caused by atrial fibrillation or atrial flutter, the chronic use of these drugs in sinus rhythm is not generally accepted. The development of tolerance has been reported. It is of interest that Withering hirnself wrote: "-let it (foxglove) be continued until it either acts on the kidneys, the stomach, the pulse, or the bowels; Iet it be stopped upon the first appearance of any of these effects, and I will maintain that the patient will not suffer from its exhibition, nor the practitioner be disappointed in any reasonable expectation. " In West Germany alone, more than three million patients (about 5% of the total population) are constantly taking cardiac glycosides. These drugs are the most prescribed medicaments in many countries. Thus, we considered it worthwhile and necessary to review in a critical way today's knowledge about the foxglove; to report new findings and to evaluate old Statements.

Throughout the past decades, the understanding of the pathophysiology of chronic heart failure and the therapeutic approach to this condition have un dergone considerable change. New developments are reported every year. Perhaps it is because of this continuing interest of researchers and physi th cians that the chapter on chronic heart failure of the 4 edition of Klinische Kardiologie has been so positively received. Several colleagues asked the authors to publish the chapter on chronic heart failure separately, because it would be more practical to use in daily work. When the request for an En glish version of this chapter reached the authors and Springer-Verlag, we were happy, on the one hand, because of the interest, but did wonder whether it would be wise to translate a typically German textbook into Eng lish. We invite you to send us your critical comments. Although Guidelines for the Treatment of Heart Failure have been pub lished recently by the WHO, by the European Society of Cardiology, and by the American Heart Association Task Force clinicians, practitioners, and stu dents still seem to need , a comprehensive view with emphasis on pathophys iology, epidemiology and therapy. The authors are grateful to Springer-Verlag for the good co-operation and tremendous personal commitment in making the English edition of Chronic Heart Failure possible. We hope to give our readers a good overview on this important clinical syndrome, one which re quires intelligent clinical research and sound clinical practice as weIl.

This volume of translations unites three shorter works by Arthur Schopenhauer that expand on themes from his book The World as Will and Representation. In On the Fourfold Root he takes the principle of sufficient reason, which states that nothing is without a reason why it is, and shows how it covers different forms of explanation or ground that previous philosophers have tended to confuse. Schopenhauer regarded this study, which he first wrote as his doctoral dissertation, as an essential preliminary to The World as Will. On Will in Nature examines contemporary scientific findings in search of corroboration of his thesis that processes in nature are all a species of striving towards ends; and On Vision and Colours defends an anti-Newtonian account of colour perception influenced by Goethe's famous colour theory. This is the first English edition to provide extensive editorial notes on the different published versions of these works.

Organische Nitratester gehoren seit uber 120 Jahren zum therapeutischen Schatz der pharmakotherapeutischen Behandlung von ischamischen Herz erkrankungen, insbesondere der koronaren Herzkrankheit (KHK). Sie gehoren zu den ersten definierten Wirkstoffverbindungen uberhaupt, die in der klini schen Medizin angewendet wurden. Die Ansichten zu ihrer Wirksamkeit gehen seit genauso langer Zeit auseinander, obwohl der therapeutische Nutzen immer wieder - so auch in jungster Zeit - beschrieben wurde und ihr Stellenwert in nationalen und internationalen Leitlinien definiert ist. Die kritische Diskussi on wird im Wesentlichen durch zwei Gesichtspunkte stimuliert, die den klini schen Einsatz von Nitrovasodilatatoren limitieren. Eine chronische Therapie mit dem am haufigsten untersuchten Glyceroltrinitrat (GTN) fuhrt zu Wir kungsabschwachung (Toleranz). Auf Grund neuerer Befunde ist dieses Phano men der Toleranz die Folge der durch GTN stimulierten verstarkten Bildung von Sauerstoffradikalen, die die NO-Bioverfugbarkeit vermindern und den Prozess der Atherogenese fordern. Fur die Compliance des Patienten ist der mit der Therapie verbundene Nitratkopfschmerz ein ausgesprochen negativer Faktor. Die mit GTN erhobenen Befunde wurden in der Vergangenheit und werden auch heute noch immer wieder auf die gesamte Klasse ubertragen. Dies ist, wie die Erfahrung mit anderen Substanzklassen (z. B. Ca-Antagonisten und Betarezeptoren-Blockern) eindeutig gezeigt hat, nicht nur wissenschaft lich unzulassig, sondern auch ausgesprochen problematisch. Fur den NO-Donor Pentaerithrityltetranitrat (PETN) konnte insbesondere im vergangenen Jahrzehnt durch methodisch einwandfreie Untersuchungen nachgewiesen werden, dass PETN weder im Tierexperiment noch unter hu manpharmakologischen Bedingungen hamodynamische Toleranz auslost. PETN fuhrt auch nicht zu einer vermehrten Bildung von Sauerstoffradikalen. Daher bleibt die NO-Bioverfugbarkeit unter PETN ungestort erhalten."

In den letzten 2 Jahrzehnten ist es gelungen, die einzigartige Bedeutung des Stickstoffmonoxid (NO) fur eine Vielzahl von biologischen Funktionen he rauszuarbeiten. Die Ergebnisse der molekularbiologischen Forschung der letzten Jahre machen es verstandlich, warum organische Nitrate seit Genera tionen erfolgreich in der Akutbehandlung und Langzeitprophylaxe der Angi na pectoris eingesetzt werden und ein unverzichtbarer Bestandteil der phar makologischen Therapiemoglichkeiten bei der Behandlung der koronaren Herzkrankheit sind. NO-Donoren aus der Gruppe der Salpetersaureester sind Pro Drugs, die eine gestorte endogene, im Wesentlichen endotheliale NO Produktion substituieren. Ausgangspunkt fur die molekularbiologische For schung uber die Wirkungen von NO waren die Ergebnisse der Forschungs arbeiten von Robert F. Furchgott. Seine Arbeitsgruppe konnte auf Grund ex perimenteller Untersuchungen die Existenz eines "endothelium-derived relax ing factor" (EDRF) postulieren. Die Gruppen von Salvator Moncada und Lou Ignarro konnten die Identitat des EDRF mit dem NO-Radikal nachweisen. Sie erhielten dafur 1998 den Nobelpreis. Dies unterstreicht die hohe klinische Relevanz der wissenschaftlichen Forschungsarbeiten mit NO. Die seit mehr als 100 Jahren therapeutisch eingesetzten organischen Nitra te haben auf Grund der intensiven experimentellen pharmakologischen Ar beiten das Stadium der Empirie verlassen und reprasentieren heute eine ra tional begrundbare Substitutionstherapie. Fur die Wirkmechanismen liegen experimentell sehr gut abgesicherte Modellvorstellungen vor. Allerdings gibt es ungeachtet vieler grundsatzlicher Gemeinsamkeiten innerhalb dieser Sub stanzklasse Unterschiede in Wirkstarke, Wirkdauer sowie zu einem gewissen Ausmass auch im Wirkort. Die pharmakokinetischen und pharmakodyna mischen Unterschiede beruhen auf unterschiedlichen physikochemischen Ei genschaften."

These two important essays show Schopenhauer at his most accessible, offering two self-contained and clearly argued contributions to ethical theory, published here in a new translation that preserves Schopenhauer's style in a lucid and engaging way. This is also the only paperback edition to publish both essays together. Schopenhauer argues, in uniquely powerful prose, that self-consciousness gives the illusion of freedom and that human actions are determined, but that we rightly feel guilt because our actions issue from our essential individual character. He locates moral value in the virtues of loving kindness and voluntary justice that spring from the fundamental incentive of compassion. Morality's basis is ultimately metaphysical, resting on an intuitive identification of the self with all other striving and suffering beings. The Introduction by leading Schopenhauer scholar Christopher Janaway gives a clear summary of the argument of the essays in the context of Schopenhauer's life and works and the history of ethics in the modern period. The volume includes helpful notes, up-to-date bibliography, and a full index.
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