Die pyloruserhaltende Whipple-Operation: eine Alternative oder heutiger Standard beim Pankreaskarzinom?

Zusammenfassung: Grundlagen: Während die pyloruserhaltende Whipple-Operation eine gute Alternative zur klassischen Operation bei periampullären Tumoren darstellt, ist das Verfahren beim Pankreaskopfkarzinom umstritten. Methodik: Wir haben die Daten von 70 Patienten mit Pankreaskopfkarzinom prospektiv im Hinblick auf die Vorteile des operativen Vorgehens und in bezug auf Lebensqualität und Überlebenszeit untersucht. Ergebnisse: Bei 44 Patienten wurde eine pyloruserhaltende Resektion durchgeführt, bei 26 Fällen eine klassische Whipple-Operation (WO) mit Lymphadenektomie. Es gab bezüglich Alter, Geschlecht und Tumorstadium keine Unterschiede in den beiden Patientengruppen. Die Mittelwerte für die Operationszeit, Blutverlust und Hospitalisationsdauer betrugen bei der pyloruserhaltenden WO 382 min, 1125 ml und 18,3 Tage und bei der klassischen WO 460 min (p<0,05), 1650 ml (p<0,05) und 22 Tage. Die mediane Überprüfzeit betrug 17 Monate (Range 2 bis 28 Monate). In den ersten 3 Monaten postoperativ war der Gewichtsverlauf bei den Patienten mit pyloruserhaltender WO deutlich besser. Die mediane Überlebenszeit war nicht signifikant verschieden mit 12,2 Monaten für die Patienten mit pyloruserhaltender WO und 12,9 Monaten bei den Patienten mit klassischer WO. Schlußfolgerungen: Bei Patienten mit Pankreaskarzinom war die Lebensqualität und Gewichtszunahme postoperativ besser bei solchen mit pyloruserhaltender partieller Duodenopankreatektomie im Vergleich zur klassischen WO. Aufgrund dieser Ergebnisse, der intraoperativen Vorteile und bei gleicher Überlebenszeit sollte dieses Operationsverfahren beim Pankreaskarzinom, wenn immer möglich, bevorzugt werde

Tetraspanin (TSP-17) Protects Dopaminergic Neurons against 6-OHDA-Induced Neurodegeneration in <i>C. elegans</i>

Parkinson's disease (PD), the second most prevalent neurodegenerative disease after Alzheimer's disease, is linked to the gradual loss of dopaminergic neurons in the substantia nigra. Disease loci causing hereditary forms of PD are known, but most cases are attributable to a combination of genetic and environmental risk factors. Increased incidence of PD is associated with rural living and pesticide exposure, and dopaminergic neurodegeneration can be triggered by neurotoxins such as 6-hydroxydopamine (6-OHDA). In C. elegans, this drug is taken up by the presynaptic dopamine reuptake transporter (DAT-1) and causes selective death of the eight dopaminergic neurons of the adult hermaphrodite. Using a forward genetic approach to find genes that protect against 6-OHDA-mediated neurodegeneration, we identified tsp-17, which encodes a member of the tetraspanin family of membrane proteins. We show that TSP-17 is expressed in dopaminergic neurons and provide genetic, pharmacological and biochemical evidence that it inhibits DAT-1, thus leading to increased 6-OHDA uptake in tsp-17 loss-of-function mutants. TSP-17 also protects against toxicity conferred by excessive intracellular dopamine. We provide genetic and biochemical evidence that TSP-17 acts partly via the DOP-2 dopamine receptor to negatively regulate DAT-1. tsp-17 mutants also have subtle behavioral phenotypes, some of which are conferred by aberrant dopamine signaling. Incubating mutant worms in liquid medium leads to swimming-induced paralysis. In the L1 larval stage, this phenotype is linked to lethality and cannot be rescued by a dop-3 null mutant. In contrast, mild paralysis occurring in the L4 larval stage is suppressed by dop-3, suggesting defects in dopaminergic signaling. In summary, we show that TSP-17 protects against neurodegeneration and has a role in modulating behaviors linked to dopamine signaling

Envelope Determinants of Equine Lentiviral Vaccine Protection

Lentiviral envelope (Env) antigenic variation and associated immune evasion present major obstacles to vaccine development. The concept that Env is a critical determinant for vaccine efficacy is well accepted, however defined correlates of protection associated with Env variation have yet to be determined. We reported an attenuated equine infectious anemia virus (EIAV) vaccine study that directly examined the effect of lentiviral Env sequence variation on vaccine efficacy. The study identified a significant, inverse, linear correlation between vaccine efficacy and increasing divergence of the challenge virus Env gp90 protein compared to the vaccine virus gp90. The report demonstrated approximately 100% protection of immunized ponies from disease after challenge by virus with a homologous gp90 (EV0), and roughly 40% protection against challenge by virus (EV13) with a gp90 13% divergent from the vaccine strain. In the current study we examine whether the protection observed when challenging with the EV0 strain could be conferred to animals via chimeric challenge viruses between the EV0 and EV13 strains, allowing for mapping of protection to specific Env sequences. Viruses containing the EV13 proviral backbone and selected domains of the EV0 gp90 were constructed and in vitro and in vivo infectivity examined. Vaccine efficacy studies indicated that homology between the vaccine strain gp90 and the N-terminus of the challenge strain gp90 was capable of inducing immunity that resulted in significantly lower levels of post-challenge virus and significantly delayed the onset of disease. However, a homologous N-terminal region alone inserted in the EV13 backbone could not impart the 100% protection observed with the EV0 strain. Data presented here denote the complicated and potentially contradictory relationship between in vitro virulence and in vivo pathogenicity. The study highlights the importance of structural conformation for immunogens and emphasizes the need for antibody binding, not neutralizing, assays that correlate with vaccine protection. © 2013 Craigo et al

Collins and Sivers asymmetries in muonproduction of pions and kaons off transversely polarised proton

Measurements of the Collins and Sivers asymmetries for charged pions and charged and neutral kaons produced in semi-inclusive deep-inelastic scattering of high energy muons off transversely polarised protons are presented. The results were obtained using all the available COMPASS proton data, which were taken in the years 2007 and 2010. The Collins asymmetries exhibit in the valence region a non-zero signal for pions and there are hints of non-zero signal also for kaons. The Sivers asymmetries are found to be positive for positive pions and kaons and compatible with zero otherwise.Comment: 15 pages, 13 figures and 1 tabl

The Effect of Genetic and Environmental Variation on Genital Size in Male Drosophila: Canalized but Developmentally Unstable

The genitalia of most male arthropods scale hypoallometrically with body size, that is they are more or less the same size across large and small individuals in a population. Such scaling is expected to arise when genital traits show less variation than somatic traits in response to factors that generate size variation among individuals in a population. Nevertheless, there have been few studies directly examining the relative sensitivity of genital and somatic traits to factors that affect their size. Such studies are key to understanding genital evolution and the evolution of morphological scaling relationships more generally. Previous studies indicate that the size of genital traits in male Drosophila melanogaster show a relatively low response to variation in environmental factors that affect trait size. Here we show that the size of genital traits in male fruit flies also exhibit a relatively low response to variation in genetic factors that affect trait size. Importantly, however, this low response is only to genetic factors that affect body and organ size systemically, not those that affect organ size autonomously. Further, we show that the genital traits do not show low levels of developmental instability, which is the response to stochastic developmental errors that also influence organ size autonomously. We discuss these results in the context of current hypotheses on the proximate and ultimate mechanisms that generate genital hypoallometry

Measurement of the charged-pion polarisability

The COMPASS collaboration at CERN has investigated pion Compton scattering, $\pi^-\gamma\rightarrow \pi^-\gamma$, at centre-of-mass energy below 3.5 pion masses. The process is embedded in the reaction $\pi^-\mathrm{Ni}\rightarrow\pi^-\gamma\;\mathrm{Ni}$, which is initiated by 190\,GeV pions impinging on a nickel target. The exchange of quasi-real photons is selected by isolating the sharp Coulomb peak observed at smallest momentum transfers, $Q^2<0.0015$\,(GeV/$c$)$^2$. From a sample of 63\,000 events the pion electric polarisability is determined to be $\alpha_\pi\ =\ (\,2.0\ \pm\ 0.6_{\mbox{\scriptsize stat}}\ \pm\ 0.7_{\mbox{\scriptsize syst}}\,) \times 10^{-4}\,\mbox{fm}^3$under the assumption$\alpha_\pi=-\beta_\pi$, which relates the electric and magnetic dipole polarisabilities. It is the most precise measurement of this fundamental low-energy parameter of strong interaction, that has been addressed since long by various methods with conflicting outcomes. While this result is in tension with previous dedicated measurements, it is found in agreement with the expectation from chiral perturbation theory. An additional measurement replacing pions by muons, for which the cross-section behavior is unambigiously known, was performed for an independent estimate of the systematic uncertainty.Comment: Published version: 9 pages, 3 figures, 1 tabl

Transverse spin effects in hadron-pair production from semi-inclusive deep inelastic scattering

First measurements of azimuthal asymmetries in hadron-pair production in deep-inelastic scattering of muons on transversely polarised ^6LiD (deuteron) and NH_3 (proton) targets are presented. The data were taken in the years 2002-2004 and 2007 with the COMPASS spectrometer using a muon beam of 160 GeV/c at the CERN SPS. The asymmetries provide access to the transversity distribution functions, without involving the Collins effect as in single hadron production. The sizeable asymmetries measured on the NH_ target indicate non-vanishing u-quark transversity and two-hadron interference fragmentation functions. The small asymmetries measured on the ^6LiD target can be interpreted as indication for a cancellation of u- and d-quark transversities.Comment: 13 pages, 4 figures, updated to the published versio

Search for exclusive photoproduction of Zc±_c^{\pm}(3900) at COMPASS

A search for the exclusive production of the $Z_c^{\pm}(3900)$ hadron by virtual photons has been performed in the channel $Z_c^{\pm}(3900)\rightarrow J/\psi \pi^{\pm}$. The data cover the range from 7 GeV to 19 GeV in the centre-of-mass energy of the photon-nucleon system. The full set of the COMPASS data set collected with a muon beam between 2002 and 2011 has been used. An upper limit for the ratio $BR(Z_c^{\pm}(3900)\rightarrow J/\psi \pi^{\pm} )\times \sigma_{ \gamma~N \rightarrow Z_c^{\pm}(3900)~ N} /\sigma_{\gamma~N \rightarrow J/\psi~ N}$ of $3.7\times10^{-3}$ has been established at the confidence level of 90%.Comment: 8 pages, 3 figures, 1 tabl

Transverse-momentum-dependent Multiplicities of Charged Hadrons in Muon-Deuteron Deep Inelastic Scattering

A semi-inclusive measurement of charged hadron multiplicities in deep inelastic muon scattering off an isoscalar target was performed using data collected by the COMPASS Collaboration at CERN. The following kinematic domain is covered by the data: photon virtuality $Q^{2}>1$ (GeV/$c$)$^2$, invariant mass of the hadronic system $W > 5$ GeV/$c^2$, Bjorken scaling variable in the range $0.003 < x < 0.4$, fraction of the virtual photon energy carried by the hadron in the range $0.2 < z < 0.8$, square of the hadron transverse momentum with respect to the virtual photon direction in the range 0.02 (GeV/$c)^2 < P_{\rm{hT}}^{2} < 3$ (GeV/$c$)$^2$. The multiplicities are presented as a function of $P_{\rm{hT}}^{2}$ in three-dimensional bins of $x$, $Q^2$, $z$ and compared to previous semi-inclusive measurements. We explore the small-$P_{\rm{hT}}^{2}$ region, i.e. $P_{\rm{hT}}^{2} < 1$ (GeV/$c$)$^2$, where hadron transverse momenta are expected to arise from non-perturbative effects, and also the domain of larger $P_{\rm{hT}}^{2}$, where contributions from higher-order perturbative QCD are expected to dominate. The multiplicities are fitted using a single-exponential function at small $P_{\rm{hT}}^{2}$ to study the dependence of the average transverse momentum $\langle P_{\rm{hT}}^{2}\rangle$ on $x$, $Q^2$ and $z$. The power-law behaviour of the multiplicities at large $P_{\rm{hT}}^{2}$ is investigated using various functional forms. The fits describe the data reasonably well over the full measured range.Comment: 28 pages, 20 figure