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Es sollte in dieser Schrift untersucht werden, inwieweit bei Änderungen im Bereich der Planung, Durchführung und Auswertung von klinischen Arzneimittelprüfungen die Bewertung mit wissenschaftlichen oder politischen Begründungen erfolgt und inwieweit wissenschaftliche Regeln für politische Zwecke genutzt werden.
Serendipities in der Medizin
(2016)
Zufälle begleiten unser Leben. Auch bei wichtigen Entdeckungen und Entwicklungen in der Medizin spielt der „Zufall“ (engl. „serendipity“) eine Rolle. Hierzu gehören u. a. die Mendelschen Gesetze, die Ermittlung der menschlichen Chromosomenzahl, die Entdeckung der DNS durch Watson und Crick, der PAP-Test oder die Entdeckung der Röntgenstrahlung und der Radioaktivität. Aber auch und gerade in der Pharmakologie gibt es viele Beispiele für Serendipitäten. Einige gehen eng mit Zufällen bei der Entdeckung der Bakteriologie einher.
Im Jahr 1504 verlor der deutsche Ritter Gottfried („Götz“) von Berlichingen seine
rechte Hand. Schon während seiner Genesung dachte er daran, die Hand zu ersetzen,
und beauftragte bald darauf die erste Handprothese, die sogenannte „Eiserne Hand“.
Jahre später wurde die aufwändigere zweite „Eiserne Hand“ gebaut. Wir haben die erste
Prothese auf der Basis früherer Literaturdaten von
Quasigroch (1982) mit Hilfe von 3-D
Computer-Aided Design (CAD) rekonstruiert. Dazu mussten einige Abmessungen angepasst
und ein paar Annahmen für das CAD-Modell gemacht werden. Die historische passive
Prothese des Götz von Berlichingen ist für die moderne Neuroprothetik interessant, da sie
eine Alternative zu komplexen invasiven Brain-Machine-Interface-Konzepten darstellen
könnte, wo diese Konzepte nicht notwendig, möglich oder vom Patienten gewünscht sind.
Auf Grundlage der Computer-Aided-Design (CAD)-rekonstruierten ersten „Eisernen Hand“ des Götz von Berlichingen wird ein umgebautes, controllergesteuertes sensomotorisches Fingersystem auf seine Funktionalität beim Greifen von unterschiedlichen Gegenständen beschrieben und geprüft. Die elektronischen Finger, die den „Pinzettengriff“ nachahmen und automatisch bei dem zuvor eingestellten Anpressdruck abschalten, bewiesen eine bemerkenswerte Alltagstauglichkeit. Das vorgestellte Grundkonzept könnte eine Alternative bei der Entwicklung einfacher und kostengünstiger, aber dennoch gut einsatzfähiger bionischer Hände sein und zeigt einmal mehr, wie historische Ideen in die Gegenwart transferiert werden können.
Concussions in sports and during recreational activities are a major source of traumatic brain injury in our society. This is mainly relevant in adolescence and young adulthood, where the annual rate of diagnosed concussions is increasing from year to year. Contact sports (e.g., ice hockey, American football, or boxing) are especially exposed to repeated concussions. While most of the athletes recover fully from the trauma, some experience a variety of symptoms including headache, fatigue, dizziness, anxiety, abnormal balance and postural instability, impaired memory, or other cognitive deficits. Moreover, there is growing evidence regarding clinical and neuropathological consequences of repetitive concussions, which are also linked to an increased risk for depression and Alzheimer’s disease or the development of chronic traumatic encephalopathy. With little contribution of conventional structural imaging (computed tomography (CT) or magnetic resonance imaging (MRI)) to the evaluation of concussion, nuclear imaging techniques (i.e., positron emission tomography (PET) and single-photon emission computed tomography (SPECT)) are in a favorable position to provide reliable tools for a better understanding of the pathophysiology and the clinical evaluation of athletes suffering a concussion.
There is increasing evidence of central hyperexcitability in chronic whiplash-associated disorders (cWAD). However, little is known about how an apparently simple cervical spine injury can induce changes in cerebral processes. The present study was designed (1) to validate previous results showing alterations of regional cerebral blood flow (rCBF) in cWAD, (2) to test if central hyperexcitability reflects changes in rCBF upon non-painful stimulation of the neck, and (3) to verify our hypothesis that the missing link in understanding the underlying pathophysiology could be the close interaction between the neck and midbrain structures. For this purpose, alterations of rCBF were explored in a case-control study using H215O positron emission tomography, where each group was exposed to four different conditions, including rest and different levels of non-painful electrical stimulation of the neck. rCBF was found to be elevated in patients with cWAD in the posterior cingulate and precuneus, and decreased in the superior temporal, parahippocampal, and inferior frontal gyri, the thalamus and the insular cortex when compared with rCBF in healthy controls. No differences in rCBF were observed between different levels of electrical stimulation. The alterations in regions directly involved with pain perception and interoceptive processing indicate that cWAD symptoms might be the consequence of a mismatch during the integration of information in brain regions involved in pain processing.
Dementia is a clinical diagnosis reflecting many possible underlying pathologies, for example, vascular dementia and neurodegenerative disorders such as frontotemporal dementia, Lewy body-type disorder or Alzheimer’s disease (AD). The breakthrough of 99mtechnetium-labelled perfusion tracers in the 1990s resulted in many SPECT studies of flow changes in AD. In the first decade of 2000, the role of perfusion SPECT was shifted from diagnosis towards differential diagnosis, parallel to the growing attention for diagnosing early stages of dementia. Previously a diagnosis based largely on a process of exclusion, new guidelines have emerged increasingly employing positive criteria to establish the diagnosis, including neuroimaging biomarkers. Nowadays, FDG PET has largely limited the role of perfusion SPECT, although it is still considered a valuable and cost-effective alternative when PET is not available.
Das 20. Jahrhundert ist geprägt von Aufsehen erregenden medizintechnischen Durchbrüchen: Von der ersten erfolgreichen Herztransplantation über die Entdeckung des Penicillins, vom Kampf gegen Infektionskrankheiten bis hin zu ersten Röntgenaufnahmen und Computer-Scans. Die Technologie und die medizinische Forschung haben in der Welt zu umwälzenden Fortschritten geführt. Krankheiten können gelindert oder sogar geheilt werden. Die Entwicklung von künstlichen Hüftgelenken, Cochlea-Implantaten sowie Herzschrittmachern sind in unserer Zeit zu alltäglichen Errungenschaften geworden. Auch die Behandlung neurologischer Bewegungsstörungen ist in den Fokus des technisch-medizinischen Fortschritts gelangt: „Hirnschrittmachersysteme“ – symptomfrei auf Knopfdruck. Ein Eingriff in das Gehirn, um gezielt elektrische Impulse abzugeben, um die Symptome beispielsweise von pharmakoresistenter Parkinsonpatienten effektiv zu behandeln. Dieses Therapieverfahren stellt für viele Patienten die letzte Möglichkeit dar, ein mehr oder weniger beschwerdefreies Leben führen zu können. Gleichzeitig ist dieses Verfahren ethisch heftig umstritten, zumal der Eingriff in das Gehirn gleichbedeutend mit einem Eingriff in den ‚Sitz des Selbst‘, der Persönlichkeit eines Patienten, verbunden ist.
Chronic insomnia is defined by difficulties in falling asleep, maintaining sleep, and early morning awakening, and is coupled with daytime consequences such as fatigue, attention deficits, and mood instability. These symptoms persist over a period of at least 3 months (Diagnostic and Statistical Manual 5 criteria). Chronic insomnia can be a symptom of many medical, neurological, and mental disorders. As a disorder, it incurs substantial health-care and occupational costs, and poses substantial risks for the development of cardiovascular and mental disorders, including cognitive deficits. Family and twin studies confirm that chronic insomnia can have a genetic component (heritability coefficients between 42% and 57%), whereas the investigation of autonomous and central nervous system parameters has identified hyperarousal as a final common pathway of the pathophysiology, implicating an imbalance of sleep–wake regulation consisting of either overactivity of the arousal systems, hypoactivity of the sleep-inducing systems, or both. Insomnia treatments include benzodiazepines, benzodiazepine-receptor agonists, and cognitive behavioural therapy. Treatments currently under investigation include transcranial magnetic or electrical brain stimulation, and novel methods to deliver psychological interventions.
Routine nuclear cardiology examinations indicate heart rate, cardiac rhythm, the height of cardiac pulse and respiration rhythm. It would be of interest to study whether these data, especially if the same tests are repeated, can indicate patients’ well being in the future and perhaps patients’ life span, other factors being equal. Related old theories and suggestions are mentioned. Furthermore, some drugs like I-f channel antagonists and stress tests testing cardiac reserves could support such a study.
In this study, we tested the function of a replica of the over 500-year-old original of the
famous Franconian Imperial Knight Götz von Berlichingen’s first “iron hand”, which we
reconstructed by computer-aided design (CAD) and recently printed using a multi-material
3D printer. In different everyday tasks, the artificial hand prosthesis proved to be remarkably
helpful. Thus, the hand could hold a wine glass, some grapes, or a smartphone. With a
suitable pencil, even writing was possible without any problem. Although for all these
functions the healthy other hand was necessary to assist at the beginning, the artificial hand
is an astonishing mechanical aid with many possibilities. Therefore, in certain cases, the
non-invasive approach of a passive mechanical hand replacement, which is an individual,
quick and cheap solution due to modern 3D printing, may always be worth considering
also for today’s requirements.
Wir haben die erste „Eiserne Hand“ des Götz von Berlichingen mit 3D-Computer-Aided Design rekonstruiert und über einen Multimaterial-3D-Drucker ausgedruckt. Dabei ließ sich feststellen, dass die 500 Jahre alte Technik keinesfalls veraltet ist: Das Innenleben der „Eisernen Hand“ ist ausgefeilter als bisher angenommen. Sie könnte sogar spannende Impulse für die Entwicklung neuer künstlicher Handprothesen liefern.
All you need is sleep
(2016)
In 21st century, the century when the humanity hopes to embark on interplanetary travel, we are yet to fully reach an understanding of our very own idiosyncratic terra incognita – the human sleep. Sleep is a highly conserved evolutionary process that constitutes approximately one third of our life, and the lack or inadequate sleep may lead to impairment across multiple cognitive domains (Tononi and Cirelli, 2014; Lim and Dinges, 2010). Sleep deprivation also leads to aberrant brain functioning, immunological and metabolic collapse, and if it is sufficiently prolonged it will ultimately lead to death (Tononi and Cirelli, 2014).
The famous violin virtuoso Nicolò Paganini (born on 27 October 1782 in Genoa, died on 27 May 1840 in Nice) left us with many puzzles. An interesting aspect is his hair: In the 19th century, hair given away as a token of friendship or romantic love became very popular, and Paganini also seems to have made use of this fad. In 2009, a lock of hair, purportedly that of Paganini, kept in a locked presentation box together with a bilingual autograph inscription saying: "Alla Signora Chatterton avec les compliments de Nicolò Paganini" was bought at an auction. From this hair lock a sample was taken and was investigated morphologically by using digital light microscopy (digital microscope VHX-100, Keyence) in reflected and transmitted light with and without polarization at different magnifications up to 1:5,000. The sample was then compared with a hair sample from the possession of the Paganini family, which had been microscopically examined in 2012 by the co-author of this paper yielding numerous figures with measurement results that had been stored and could be retrieved for direct comparison. The hair sample consisted of ten strands of hair or hair fragments and was investigated with great effort for the following parameters: exogenous hair damage, especially feeding traces caused by parasites, modeling and angulation of hairs, hair thickness, medulla and pigmentation, curling and mercury load on the trace material. After evaluation of all findings not only a non-exclusion of identity can be determined, but due to the broad match of also rare findings there is no reasonable doubt about their identity. In addition, the findings suggest that the studied hair samples are in fact from Paganini's head. The present case of Nicolò Paganini's hair lock is also an excellent starting point for reflections on the probative value of trace hair investigations. This point is also critically discussed in the paper. Finally, this study shows that said lock of hair had probably really been dedicated and given to Eliza Davenport Latham (born on 25 November 1806, died on 9 January 1877), the future wife of the, at that time, best-known and most famous English harpist John Balsir Chatterton (born on 25 November 1804, died on 9 April 1871). Paganini must have met her on his concert tour 1831/32, where he had travelled to Paris, London, the rest of England, Scotland and Ireland.
Cardiac resynchronisation therapy (CRT) is a promising treatment option in patients with chronic heart failure. In this article the roles of semi-invasive esophageal left-heart electrocardiography and functional cardiac nuclear imaging in the field of CRT are highlighted, as the combination of both could be a favourable diagnostic approach in special cardiac situations. Also original esophageal left heart electrogram data of exemplary CRT patients is presented.
Hybrid SPECT/US
(2014)
eLetter zum Artikel "Hybrid EEG/EOG-based brain/neural hand exoskeleton restores fully independent daily living activities after quadriplegia" von Surjo R. Soekadar et al., veröffentlicht in Science Robotics, Vol. 1, No. 1 (DOI: 10.1126/scirobotics.aag3296)
Nicht-invasives, nicht-ionisierendes funktionelles Neuroimaging mit räumlich und zeitlich hochauflösender Elektroenzephalographie oder Echtzeit-Naheinfrarotspektroskopie in Kombination mit modernen Robotorsystemen ist ein entscheidender Entwicklungsschritt auf dem Gebiet der Neuroprothetik und Brain-Machine-Interfaces. In der Medizintechnik an der Hochschule Offenburg wird hierzu geforscht.
Im Archiv für Kriminologie wurden bislang drei Arbeiten zur 3-D-CAD-Rekonstruktion der ersten "Eisernen Hand" des berühmten Reichsritters Gottfried ("Götz") von Berlichingen (1480-1562) vorgestellt. Mittlerweile sind einige neue Gesichtspunkte herausgearbeitet worden, die hier kurz als Ergänzung mitgeteilt werden sollen.
"Ad fontes!"
Francesco Petrarca (1301–1374)
In the beginning, there was an idea: the reconstruction of the first "Iron Hand" of the Franconian imperial knight Götz von Berlichingen (1480–1562). We found that with this historical prosthesis, simple actions for daily use, such as holding a wine glass, a mobile phone, a bicycle handlebar grip, a horse’s reins, or some grapes, are possible without effort. Controlling this passive artificial hand, however, is based on the help of a healthy second hand.
Geleitwort
(2012)