Operative Therapie von akral lokalisierten Melanomen

Zusammenfassung: Akrolentiginöse Melanome (ALM) umfassen 4-10% der kutanen Melanome bei Hellhäutigen. Patienten mit ALM wird oft eine schlechtere Prognose zugeschrieben, meist aufgrund zu später Diagnosestellung. Unter Einsatz der 3D-Histologie können akral lokalisierte Melanome mit kontinuierlichem Ausbreitungsmuster lokal chirurgisch mit kleineren Sicherheitsabständen und einem guten funktionellen und kosmetischen Ergebnis behandelt werden. In einer Studie wurden bei 244Patienten mit ALM die konventionelle Histologie vs. 3D-Histologie neben anderen prognostischen Parametern verglichen. Klinische und chirurgische Risikofaktoren beeinflussen die Prognose des ALM. Tumordicke und Ulzeration sind die wichtigsten Risikofaktoren. Die 3D-Histologie in Paraffintechnik ermöglicht es, Sicherheitsabstände zu reduzieren und Lokalrezidive zu vermeiden. Subunguale Melanome machen nur etwa 2-3% der kutanen Melanome beim kaukasischen und etwa 20% der Melanome beim afrikanischen oder asiatischen Hauttyp aus und werden klinisch häufig fehldiagnostiziert. Sie sind oft an Daumen und Großzehe lokalisiert. Die Entfernung von subungualen Melanomen mit 3D-Histologie und tumorfreien Schnitträndern unter Einschluss der Nagelmatrix kann als sichere Strategie angesehen werden, welche die Prognose nicht beeinträchtigt. Funktion und Kosmetik eines Fingers oder Zehs bleiben erhalten. Amputationen bei subungualen Melanomen sollten fortgeschrittenen Verläufen mit Knochen- oder Gelenkbefall vorbehalten bleibe

Quantum Fields a la Sylvester and Witt

A structural explanation of the coupling constants in the standard model, i.e the fine structure constant and the Weinberg angle, and of the gauge fixing contributions is given in terms of symmetries and representation theory. The coupling constants are normalizations of Lorentz invariantly embedded little groups (spin and polarization) arising in a harmonic analysis of quantum vector fields. It is shown that the harmonic analysis of massless fields requires an extension of the familiar Fourier decomposition, containing also indefinite unitary nondecomposable time representations. This is illustrated by the nonprobabilistic contributions in the electromagnetic field.Comment: 18 pages LaTeX file (62 kB), all macros are include

Prognosis of Sentinel Node Staged Patients with Primary Cutaneous Melanoma

Background: This study investigated survival probabilities and prognostic factors in sentinel lymph node biopsy (SLNB) staged patients with cutaneous melanoma (CM) with the aim of defining subgroups of patients who are at higher risk for recurrences and who should be considered for adjuvant clinical trials.\ud \ud Methods: Patients with primary CM who underwent SLNB in the Department of Dermatology, University of Tuebingen, Germany, between 1996 and 2009 were included into this study. Survival probabilities and prognostic factors were evaluated by Kaplan-Meier and multivariate Cox proportional hazard models.\ud \ud Results: 1909 SLNB staged patients were evaluated. Median follow-up time was 44 months. Median tumor thickness was 1.8 mm, ulceration was present in 31.8% of cases. The 5-year Overall Survival (OS) was 90.3% in SLNB negative patients (IB 96.2%, IIA 87.0%, IIB 78.1%, IIC 72.6%). Patients with micrometastases (stage IIIA/B) had a 5-year OS rate of 70.9% which was clearly less favorable than for stages I–II. Multivariate analysis revealed tumor thickness, ulceration, body site, histopathologic subtype and SLNB status as independent significant prognostic factors.\ud \ud Conclusion: Survival rates of patients with primary CM in stages I–II were shown to be much more favorable than previously reported from non sentinel node staged collectives. For future clinical trials, sample size calculations should be adapted using survival probabilities based on sentinel node staging

Cytotoxicity of rhein, the active metabolite of sennoside laxatives, is reduced by multidrug resistance-associated protein 1

Anthranoid laxatives, belonging to the anthraquinones as do anthracyclines, possibly increase colorectal cancer risk. Anthracyclines interfere with topoisomerase II, intercalate DNA and are substrates for P-glycoprotein and multidrug resistance-associated protein 1. P-glycoprotein and multidrug resistance-associated protein 1 protect colonic epithelial cells against xenobiotics. The aim of this study was to analyse the interference of anthranoids with these natural defence mechanisms and the direct cytotoxicity of anthranoids in cancer cell lines expressing these mechanisms in varying combinations. A cytotoxicity profile of rhein, aloe emodin and danthron was established in related cell lines exhibiting different levels of topoisomerases, multidrug resistance-associated protein 1 and P-glycoprotein. Interaction of rhein with multidrug resistance-associated protein 1 was studied by carboxy fluorescein efflux and direct cytotoxicity by apoptosis induction. Rhein was less cytotoxic in the multidrug resistance-associated protein 1 overexpressing GLC4/ADR cell line compared to GLC4. Multidrug resistance-associated protein 1 inhibition with MK571 increased rhein cytotoxicity. Carboxy fluorescein efflux was blocked by rhein. No P-glycoprotein dependent rhein efflux was observed, nor was topoisomerase II responsible for reduced toxicity. Rhein induced apoptosis but did not intercalate DNA. Aloe emodin and danthron were no substrates for MDR mechanisms. Rhein is a substrate for multidrug resistance-associated protein 1 and induces apoptosis. It could therefore render the colonic epithelium sensitive to cytotoxic agents, apart from being toxic in itself

Inhibition decorrelates visual feature representations in the inner retina

The retina extracts visual features for transmission to the brain. Different types of bipolar cell split the photoreceptor input into parallel channels and provide the excitatory drive for downstream visual circuits. Mouse bipolar cell types have been described at great anatomical and genetic detail, but a similarly deep understanding of their functional diversity is lacking. Here, by imaging light-driven glutamate release from more than 13,000 bipolar cell axon terminals in the intact retina, we show that bipolar cell functional diversity is generated by the interplay of dendritic excitatory inputs and axonal inhibitory inputs. The resulting centre and surround components of bipolar cell receptive fields interact to decorrelate bipolar cell output in the spatial and temporal domains. Our findings highlight the importance of inhibitory circuits in generating functionally diverse excitatory pathways and suggest that decorrelation of parallel visual pathways begins as early as the second synapse of the mouse visual system