Zugl.: München, Univ., Diss., 2004

Tübingen, Univ., Diss., 2006.

Hintergrund. Untersuchungen bei Patienten mit funktionellen Mutationen des Noradrenalin-Transporter-Gens deuten darauf hin, dass eine verminderte Noradrenalin-Wiederaufnahme zur Pathophysiologie der idiopathischen Orthostatischen Intoleranz beitragen kann. Methoden. In einer doppeltblinden, placebokontrollierten, randomisierten Studie wurden die kardiovaskulären Effekte einer selektiven pharmakologischen Noradrenalin-Wiederaufnahmehemmung (2x 8 mg Reboxetin p.o.) bei gesunden Testpersonen untersucht. In der ersten Teilstudie (n=23) wurden autonome Funktionstests und eine Kipptischuntersuchung durchgeführt. Herzfrequenz, Blutdruck und zerebrale Blutflussgeschwindigkeit wurden dabei kontinuierlich nicht-invasiv gemessen. Herzzeitvolumen und peripherer Widerstand wurden impedanzkardiografisch bestimmt. In einer zweiten Teilstudie (n=10) wurde der Effekt akuter selektiver Noradrenalin-Wiederaufnahmehemmung auf die Sensitivität gegenüber blutdruckwirksamer Pharmaka getestet. Dafür wurden steigende intravenöse Dosen von Phenylephrin, Isoproterenol und Nitroprussid gegeben und die Änderungen von Blutdruck und Herzfrequenz in individuellen Dosis-Wirkungskurven bestimmt. Ergebnisse. Unter Noradrenalin-Wiederaufnahmehemmung waren Herzfrequenz und Blutdruck im Liegen erhöht. Während der Kipptischuntersuchung führte die Noradrenalin-Wiederaufnahmehemmung zu einer deutlich gesteigerten Herzfrequenz (120+/-3 /min vs. 83+/-3 /min unter Placebo, p / Background. Observations in patients with functional mutations of the norepinephrine transporter (NET) gene suggest that impaired norepinephrine uptake may contribute to idiopathic orthostatic intolerance. Methods. In a double-blind, placebo-controlled, and randomized crossover study we investigated the cardiovascular effects of acute selective pharmacological inhibition of the norepinephrine transporter (2x 8mg reboxetine p.o.) on healthy volunteers. Autonomic function test and a graded head-up tilt test were performed (n=23). Heart rate, blood pressure and cerebral blood flow velocity were measured non-invasively and continuously. Cardiac output and peripheral resistance were measured by impedance cardiography. In a smaller subset of volunteers (n=10) we also investigated the effects of acute inhibition of the Norepinephrine transporter on the sensitivity to pressor and depressor agents. Therefore, increasing doses of phenylephrine, isoproterenol, and nitroprusside were administered intravenously and individual dose-response-curves were plotted. Results. Norepinephrine reuptake inhibition increased both, supine heart rate and blood pressure. During head-up tilt, heart rate was profoundly increased with norepinephrine reuptake inhibition (120+/-3 /min vs. 83+/-3 /min with placebo, p

Swedish has a contrast between two so-called tonal word accents: accent 1 and accent 2. In central standard Swedish, for example, compound words generally have accent 2 and primary stress on the first element. In contrast, traditional Scanian dialects exhibit both a high occurrence of accent 1 in compounds and dialect geographic variation between accent 2 and second element stress. This dissertation argues in favour of four diachronically oriented hypotheses pertaining to the word accent distribution in compounds with monosyllabic first elements in these dialects: (1) compounds emanating from syntactic juxtapositions have accent 1; (2) compounds formed by way of compounding proper (stem compounds and comparable formations) have accent 2 or second-element stress; (3) compounds of either of these two types do, however, have accent 1 if the first element was originally disyllabic and has lost its posttonic syllable through syncope; (4) West Germanic loanwords have accent 1. This permits the generalisation that postlexical accent 2, which applies generally in compounds in central standard Swedish, for example, only applies in (non-syncopated) compounds proper in Scanian dialects, while in the other categories the word accent follows from the first element. The larger dialect geographical picture in Sweden is discussed, and it is concluded that the system found in Scanian and many other dialects represents the original state of affairs in Scandinavia as a whole, while the central standard Swedish system with general accent 2 in compounds is an innovation. The dissertation also gives a dialect geographical account of second-element stress, which, in agreement with previous research, is found to be primarily a south Scanian but to some degree also a north-west Scanian phenomenon. It is further proposed that Scanian second-element stress originated in an accent-2 curve with the floating prominence tone H (entailing the curve’s F0 maximum) timed with the posttonic syllable, by way of association of the prominence tone to the posttonic syllable. This curve is documented in south­-east Scania and is hypothesised to have earlier been spread throughout southern and western Scania.