Anthrazykline und Herceptin® als neue Therapieoption beim metastasierten Mammakarzinom

Single-agent treatment with the humanized monoclonal antibody trastuzumab (herceptin) has shown remarkable activity in patients with metastatic breast cancer overexpressing the HER-2/neu proto-oncogen. Further significant advances could be achieved with the combined use of herceptin and paclitaxel or doxorubicin/cyclophosphamide. However, cardiotoxicity remains a significant and thus far unresolved problem of the herceptin-doxo-rubicin combination. Thus, several studies have recently been initiated to identify equally effective but less toxic first-line regimens. Epirubicin, the taxanes paclitaxel and docetaxel, Navelbine(R), cisplatin, and Caelyx(R), a liposomal encapsulated formulation of doxorubicin, were selected for combination with herceptin in these studies because the appeared the most promising agents

Retrospektive Analyse zur Dosisintensität von Epirubicin beim Mammakarzinom

Objective: In breast cancer the efficacy of epirubicin-based chemotherapy is possibly related to the actual dose intensity applied. We retrospectively determined the administered dose intensity and the relative toxicity and efficacy of an epirubicin-containing regimen in patients with primary or metastatic breast cancer. Patients and Methods: Fluorouracil, epirubicin, and cyclophosphamide (FEC) were either given at a standard dose of 500/50/500 mg/m(2) (FE50C) or at an intensified dose of 500/75/500 mg/m(2) (FE75C) every 3 weeks. Of the 66 patients treated, 63 were evaluable; 43 had metastatic breast cancer, and 20 patients with an increased risk of relapse received FEC as an adjuvant treatment. Results: Dose intensity and absolute dose of adjuvant treatment were 81 and 70% for FE50C and 96 and 88% for FE75C In metastatic breast cancer, the dose intensity for FE50C was 94% and for FE75C 92%. In a retrospective comparison, the 4-year overall survival following adjuvant FE50C and FE75C was 40 and 48%, respectively (p = 0.47). The dose intensification led to a higher response rate of 34 vs. 44%. There were no significant differences in response duration and survival time. The toxicity profiles were comparable between FE50C and FE75C Conclusions: In genera I, the doses applied were lower than initially planned. Higher doses of epirubicin did not result in a significant increase of toxicity. Despite the limitations of a retrospective analysis, our observations support the importance of adherence to the planned dose intensity as a prerequisite for optimal treatment of patients suffering from breast cancer. As our results could be related to selection bias, dose-intensified anthracycline-containing regimens should be further evaluated in prospective trials. Copyright (C) 2001 S. Karger AG, Basel

Transport properties of chemically synthesized polypyrrole thin films

The electronic transport in polypyrrole thin films synthesized chemically from the vapor phase is studied as a function of temperature as well as of electric and magnetic fields. We find distinct differences in comparison to the behavior of both polypyrrole films prepared by electrochemical growth as well as of the bulk films obtained from conventional chemical synthesis. For small electric fields F, a transition from Efros-Shklovskii variable range hopping to Arrhenius activated transport is observed at 30 K. High electric fields induce short range hopping. The characteristic hopping distance is found to be proportional to F^(-1/2). The magnetoresistance R(B) is independent of F below a critical magnetic field, above which F counteracts the magnetic field induced localization.Comment: 6 pages, 5 figure

'I like money, I like many things'. The relationship between drugs and crime from the perspective of young people in contact with criminal justice systems

Based on research undertaken as part of the EU funded EPPIC project, this paper aims to update and elaborate on the relationship between drug use and offending behaviours by exploring variations within a cross-national sample of drug-experienced young people in touch with criminal justice systems. Adopting a trajectory-based approach, interviews were undertaken with 198 young people aged 15–25 in six European countries (Austria, Denmark, Germany, Italy, Poland, and UK). Data were analysed by applying the Bennett and Holloway categorization of the drugs-crime link, with a focus on the concept of social exclusion as developed by Seddon. Three main types of mechanisms (economic, pharmaceutical, and lifestyles) are used to interpret the data, showing how the relationship between drugs and offending can vary according to type of substances and over time. Furthermore, it can be associated with very different degrees of social exclusion and needs. The results suggest that while economic inequalities still play key roles in explaining drug use and offending, both behaviours can originate from a state of relative deprivation, resulting from the contradictions inherent in ‘bulimic societies’ that raise aspirations and desires while providing young people scarce opportunities for self-realisation and social recognition

Leptospirosis followed by Kawasaki-like disease: case report from an adult Swiss patient and review of the literature

Kawasaki disease (KD) is a vasculitis that mostly occurs in children, but rare cases in adults have been reported. We describe the case of a 43-year-old Swiss male who developed symptoms compatible with KD 7 weeks after leptospirosis, which was presumably acquired after swimming in a creek in the Swiss Alps. We performed a literature review and identified 10 other cases (all in children), in which Kawasaki-like disease was diagnosed in the context of leptospirosis. Outcome was favourable in most cases, including our patient. This exceptional case demonstrates both the possibility of autochthonous cases of leptospirosis in Switzerland as well as a possible association of leptospirosis with Kawasaki-like disease

The Gut Microbiome in Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS)

Myalgic encephalomyelitis (ME) or Chronic Fatigue Syndrome (CFS) is a neglected, debilitating multi-systemic disease without diagnostic marker or therapy. Despite evidence for neurological, immunological, infectious, muscular and endocrine pathophysiological abnormalities, the etiology and a clear pathophysiology remains unclear. The gut microbiome gained much attention in the last decade with manifold implications in health and disease. Here we review the current state of knowledge on the interplay between ME/CFS and the microbiome, to identify potential diagnostic or interventional approaches, and propose areas where further research is needed. We iteratively selected and elaborated on key theories about a correlation between microbiome state and ME/CFS pathology, developing further hypotheses. Based on the literature we hypothesize that antibiotic use throughout life favours an intestinal microbiota composition which might be a risk factor for ME/CFS. Main proposed pathomechanisms include gut dysbiosis, altered gut-brain axis activity, increased gut permeability with concomitant bacterial translocation and reduced levels of short-chain-fatty acids, D-lactic acidosis, an abnormal tryptophan metabolism and low activity of the kynurenine pathway. We review options for microbiome manipulation in ME/CFS patients including probiotic and dietary interventions as well as fecal microbiota transplantations. Beyond increasing gut permeability and bacterial translocation, specific dysbiosis may modify fermentation products, affecting peripheral mitochondria. Considering the gut-brain axis we strongly suspect that the microbiome may contribute to neurocognitive impairments of ME/CFS patients. Further larger studies are needed, above all to clarify whether D-lactic acidosis and early-life antibiotic use may be part of ME/CFS etiology and what role changes in the tryptophan metabolism might play. An association between the gut microbiome and the disease ME/CFS is plausible. As causality remains unclear, we recommend longitudinal studies. Activity levels, bedridden hours and disease progression should be compared to antibiotic exposure, drug intakes and alterations in the composition of the microbiota. The therapeutic potential of fecal microbiota transfer and of targeted dietary interventions should be systematically evaluated

Unintended consequences of drug policies experienced by young drug users in contact with the criminal justice systems

The aim of this paper is to assess to what extent prohibitive drug policies hamper the management of drug problems from the perspective of young people who have experience with the criminal justice systems (CJS). Qualitative, in-depth interviews were carried out in six European countries (Austria, Denmark, Germany, Italy, Poland, and the UK) following a common interview guide to obtain comparative data on the life trajectories of drug experienced youth. Altogether 198 interviews with people aged 14–25 years were collected and analysed by national teams following a common coding book. Unintended consequences of drug policies for the individual and society were identified. Individual consequences included health consequences and traumatic experiences with law enforcement. Social consequences included those affecting social relations such as stigmatisation and those impacting on institutions, for example, focusing on drug use and neglecting other problems. This paper confirmed earlier research indicating unintended consequences of prohibitive drug policies but also added to the literature its cross-national perspective and use of young people narratives as a source of analyses. There are, however, policy measures available that may reduce the volume and range of unintended effects. Their implementation is crucial to reduce the array of unintended consequences of prohibitive drug policies

Rapid, label-free classification of glioblastoma differentiation status combining confocal Raman spectroscopy and machine learning

Label-free identification of tumor cells using spectroscopic assays has emerged as a technological innovation with a proven ability for rapid implementation in clinical care. Machine learning facilitates the optimization of processing and interpretation of extensive data, such as various spectroscopy data obtained from surgical samples. The here-described preclinical work investigates the potential of machine learning algorithms combining confocal Raman spectroscopy to distinguish non-differentiated glioblastoma cells and their respective isogenic differentiated phenotype by means of confocal ultra-rapid measurements. For this purpose, we measured and correlated modalities of 1146 intracellular single-point measurements and sustainingly clustered cell components to predict tumor stem cell existence. By further narrowing a few selected peaks, we found indicative evidence that using our computational imaging technology is a powerful approach to detect tumor stem cells in vitro with an accuracy of 91.7% in distinct cell compartments, mainly because of greater lipid content and putative different protein structures. We also demonstrate that the presented technology can overcome intra- and intertumoral cellular heterogeneity of our disease models, verifying the elevated physiological relevance of our applied disease modeling technology despite intracellular noise limitations for future translational evaluatio

Towards real-time cardiovascular magnetic resonance guided transarterial CoreValve implantation: in vivo evaluation in swine

<p>Abstract</p> <p>Background</p> <p>Real-time cardiovascular magnetic resonance (rtCMR) is considered attractive for guiding TAVI. Owing to an unlimited scan plane orientation and an unsurpassed soft-tissue contrast with simultaneous device visualization, rtCMR is presumed to allow safe device navigation and to offer optimal orientation for precise axial positioning. We sought to evaluate the preclinical feasibility of rtCMR-guided transarterial aortic valve implatation (TAVI) using the nitinol-based Medtronic CoreValve bioprosthesis.</p> <p>Methods</p> <p>rtCMR-guided transfemoral (n = 2) and transsubclavian (n = 6) TAVI was performed in 8 swine using the original CoreValve prosthesis and a modified, CMR-compatible delivery catheter without ferromagnetic components.</p> <p>Results</p> <p>rtCMR using TrueFISP sequences provided reliable imaging guidance during TAVI, which was successful in 6 swine. One transfemoral attempt failed due to unsuccessful aortic arch passage and one pericardial tamponade with subsequent death occurred as a result of ventricular perforation by the device tip due to an operating error, this complication being detected without delay by rtCMR. rtCMR allowed for a detailed, simultaneous visualization of the delivery system with the mounted stent-valve and the surrounding anatomy, resulting in improved visualization during navigation through the vasculature, passage of the aortic valve, and during placement and deployment of the stent-valve. Post-interventional success could be confirmed using ECG-triggered time-resolved cine-TrueFISP and flow-sensitive phase-contrast sequences. Intended valve position was confirmed by ex-vivo histology.</p> <p>Conclusions</p> <p>Our study shows that rtCMR-guided TAVI using the commercial CoreValve prosthesis in conjunction with a modified delivery system is feasible in swine, allowing improved procedural guidance including immediate detection of complications and direct functional assessment with reduction of radiation and omission of contrast media.</p