Normales Knochenmark und häufige reaktive Veränderungen

Zusammenfassung: Die histologische Knochenmarkuntersuchung spielt, wegen ihrer großen Aussagekraft bei relativ geringem Aufwand eine bedeutende Rolle in der Diagnostik von hämatologischen und nichthämatologischen Erkrankungen. Dafür ist die Kenntnis des normalen Knochenmarks mit seiner individuellen, insbesondere altersabhängigen, Variabilität, unentbehrlich. Neben entnahmebedingten Artefakten, die falsch interpretiert werden können, oder suboptimal fixierten bzw. verarbeiteten Biopsien, die diagnostisch überbewertet werden, gibt es eine Vielfalt von reaktiven Knochenmarkveränderungen, die einen neoplastischen Prozess vortäuschen und zu schwerwiegenden diagnostischen Fehlern führen können. Bei derartigen nichtneoplastischen Veränderungen können ein oder auch mehrere Kompartimente der Hämatopoiese qualitativ und quantitativ betroffen sein. Es kann zu Verteilungs- bzw. Architekturstörungen und/oder zu Veränderungen des Knochenmarkstromas kommen. Eine optimale Knochenmarkdiagnostik erfordert, neben Spezialfärbungen, zusätzlich oftmals immunhistochemische Untersuchungen und manchmal molekularpathologische Analysen. Mehr als bei anderen Organbiopsien ist die Kenntnis klinischer Befunde, insbesondere vorangegangener Therapien, relevant, um eine korrekte Diagnose zu stellen. In diesem Beitrag sind neben dem normalen Knochenmark die häufigsten reaktiven Veränderungen dargestell

Work-to-family enrichment and gender inequalities in eight European countries

All social roles have positive and rewarding as well as negative/problematic aspects. Research on the work–family interface has predominantly focused on conflicting roles. In contrast, this paper extends research on work–family enrichment (WFE), a positive aspect of work and gender differences in WFE in a cross-national context. Drawing upon social role theory and the culture sensitive theory on work–family enrichment, we examined gender differences in experiences of developmental WFE in a sample of service sector employees in eight European countries. In line with traditional gender roles, women reported more WFE than men. The relationship was moderated by both an objective and subjective measure of gender egalitarianism but in the opposite direction as hypothesized. The gender gap in WFE was larger in more gender-egalitarian countries, where women may be better able to transfer resources from the work domain to benefit their family role than in low egalitarian societies. National differences in labour market factors, family models and the public discourse on work–life balance mainly explain the unanticipated findings

Longitudinal photocurrent spectroscopy of a single GaAs/AlGaAs v-groove quantum wire

Modulation-doped GaAs v-groove quantum wires (QWRs) have been fabricated with novel electrical contacts made to two-dimensional electron-gas (2DEG) reservoirs. Here, we present longitudinal photocurrent (photoconductivity/PC) spectroscopy measurements of a single QWR. We clearly observe conductance in the ground-state one-dimensional subbands; in addition, a highly temperature-dependent response is seen from other structures within the v-groove. The latter phenomenon is attributed to the effects of structural topography and localization on carrier relaxation. The results of power-dependent PC measurements suggest that the QWR behaves as a series of weakly interacting localized states, at low temperatures

Crohn's disease activity index and Vienna classification - Is it worthwhile to calculate before surgery?

Background: Crohn's disease (CD) patients with increased disease activity may reveal an increased risk for perioperative complications. The `Crohn's disease activity index' (CDAI) and the `Vienna classification' (VC) were developed for standardized disease activity estimations. The significance of these scores to predict extent, type and early outcome of surgery in CD patients was analyzed. Methods: In 179 surgically treated CD patients, the CDAI and VC were assessed from a prospective database. Relations of the scores with CD risk factors, type, number, location and complications of surgery were analyzed. Results: VC behavior and location subtypes were associated with distinct types of surgery (i.e. `strictureplasty' in `stricturing disease', `colon surgery' in `colon involvement'), but not with surgery type and extent or outcome. Surgery extent (i.e. with 5 vs. 3 `surgical sites' 425 +/- 25 vs. 223.3 +/- 25) and complications (357.1 +/- 36.9 (with) vs. 244.4 +/- 13 (without)) were associated with elevated CDAI levels; however, nicotine abuse remained the only significant risk factor for perioperative complications after multiple logistic regression. Conclusion: The significance of VC or CDAI for predicting the extent of surgery or complications is limited. None of the tested variables except preoperative nicotine abuse influenced the likelihood for perioperative complications. Copyright (c) 2006 S. Karger AG, Base

Pharmacoeconomic analysis of adjuvant oral capecitabine vs intravenous 5-FU/LV in Dukes' C colon cancer: the X-ACT trial

Oral capecitabine (Xeloda<sup>®</sup>) is an effective drug with favourable safety in adjuvant and metastatic colorectal cancer. Oxaliplatin-based therapy is becoming standard for Dukes' C colon cancer in patients suitable for combination therapy, but is not yet approved by the UK National Institute for Health and Clinical Excellence (NICE) in the adjuvant setting. Adjuvant capecitabine is at least as effective as 5-fluorouracil/leucovorin (5-FU/LV), with significant superiority in relapse-free survival and a trend towards improved disease-free and overall survival. We assessed the cost-effectiveness of adjuvant capecitabine from payer (UK National Health Service (NHS)) and societal perspectives. We used clinical trial data and published sources to estimate incremental direct and societal costs and gains in quality-adjusted life months (QALMs). Acquisition costs were higher for capecitabine than 5-FU/LV, but higher 5-FU/LV administration costs resulted in 57% lower chemotherapy costs for capecitabine. Capecitabine vs 5-FU/LV-associated adverse events required fewer medications and hospitalisations (cost savings £3653). Societal costs, including patient travel/time costs, were reduced by >75% with capecitabine vs 5-FU/LV (cost savings £1318), with lifetime gain in QALMs of 9 months. Medical resource utilisation is significantly decreased with capecitabine vs 5-FU/LV, with cost savings to the NHS and society. Capecitabine is also projected to increase life expectancy vs 5-FU/LV. Cost savings and better outcomes make capecitabine a preferred adjuvant therapy for Dukes' C colon cancer. This pharmacoeconomic analysis strongly supports replacing 5-FU/LV with capecitabine in the adjuvant treatment of colon cancer in the UK

Avalanche amplification of a single exciton in a semiconductor nanowire

Interfacing single photons and electrons is a crucial ingredient for sharing quantum information between remote solid-state qubits. Semiconductor nanowires offer the unique possibility to combine optical quantum dots with avalanche photodiodes, thus enabling the conversion of an incoming single photon into a macroscopic current for efficient electrical detection. Currently, millions of excitation events are required to perform electrical read-out of an exciton qubit state. Here we demonstrate multiplication of carriers from only a single exciton generated in a quantum dot after tunneling into a nanowire avalanche photodiode. Due to the large amplification of both electrons and holes (> 10^4), we reduce by four orders of magnitude the number of excitation events required to electrically detect a single exciton generated in a quantum dot. This work represents a significant step towards single-shot electrical read-out and offers a new functionality for on-chip quantum information circuits

Radiofrequency-induced thermotherapy of nasopharyngeal angiofibroma and immunohistochemical analysis of vessel proliferation: a case report

<p>Abstract</p> <p>Introduction</p> <p>Nasopharyngeal angiofibroma presents with symptoms of nasal obstruction and epistaxis. The treatment of choice is embolization followed by surgery.</p> <p>Case presentation</p> <p>A 52-year-old man underwent surgery for nasopharyngeal angiofibroma after adjuvant radiofrequency-induced thermotherapy. To the best of the authors' knowledge, this is the first case of angiofibroma with clinical follow-up after thermocoagulation therapy supported by quantitative, double immunohistochemistry. We found this case of angiofibroma to be of interest owing to the presentation of symptoms leading to biopsy, the pathohistological observations obtained with synchronous Ki67/cluster of differentiation 34 and Ki67/smooth muscle actin immunohistochemistry and high pericyte proliferation.</p> <p>Conclusion</p> <p>Coagulation of angiofibroma vessels followed by acquisition of a thick mantle of pericytes in a patient with a nasopharyngeal growth suggests that radiofrequency-induced thermotherapy could be a useful, palliative therapy for bleeding nasopharyngeal angiofibroma, supporting vessel maturation prior to surgical tumor removal.</p

Placental syncytiotrophoblast constitutes a major barrier to vertical transmission of Listeria monocytogenes.

Listeria monocytogenes is an important cause of maternal-fetal infections and serves as a model organism to study these important but poorly understood events. L. monocytogenes can infect non-phagocytic cells by two means: direct invasion and cell-to-cell spread. The relative contribution of each method to placental infection is controversial, as is the anatomical site of invasion. Here, we report for the first time the use of first trimester placental organ cultures to quantitatively analyze L. monocytogenes infection of the human placenta. Contrary to previous reports, we found that the syncytiotrophoblast, which constitutes most of the placental surface and is bathed in maternal blood, was highly resistant to L. monocytogenes infection by either internalin-mediated invasion or cell-to-cell spread. Instead, extravillous cytotrophoblasts-which anchor the placenta in the decidua (uterine lining) and abundantly express E-cadherin-served as the primary portal of entry for L. monocytogenes from both extracellular and intracellular compartments. Subsequent bacterial dissemination to the villous stroma, where fetal capillaries are found, was hampered by further cellular and histological barriers. Our study suggests the placenta has evolved multiple mechanisms to resist pathogen infection, especially from maternal blood. These findings provide a novel explanation why almost all placental pathogens have intracellular life cycles: they may need maternal cells to reach the decidua and infect the placenta

Human gene-engineered calreticulin mutant stem cells recapitulate MPN hallmarks and identify targetable vulnerabilities

Calreticulin (CALR) mutations present the main oncogenic drivers in JAK2 wildtype (WT) myeloproliferative neoplasms (MPN), including essential thrombocythemia and myelofibrosis, where mutant (MUT) CALR is increasingly recognized as a suitable mutation-specific drug target. However, our current understanding of its mechanism-of-action is derived from mouse models or immortalized cell lines, where cross-species differences, ectopic over-expression and lack of disease penetrance are hampering translational research. Here, we describe the first human gene-engineered model of CALR MUT MPN using a CRISPR/Cas9 and adeno-associated viral vector-mediated knock-in strategy in primary human hematopoietic stem and progenitor cells (HSPCs) to establish a reproducible and trackable phenotype in vitro and in xenografted mice. Our humanized model recapitulates many disease hallmarks: thrombopoietin-independent megakaryopoiesis, myeloid-lineage skewing, splenomegaly, bone marrow fibrosis, and expansion of megakaryocyte-primed CD41+ progenitors. Strikingly, introduction of CALR mutations enforced early reprogramming of human HSPCs and the induction of an endoplasmic reticulum stress response. The observed compensatory upregulation of chaperones revealed novel mutation-specific vulnerabilities with preferential sensitivity of CALR mutant cells to inhibition of the BiP chaperone and the proteasome. Overall, our humanized model improves purely murine models and provides a readily usable basis for testing of novel therapeutic strategies in a human setting.Johannes Foßelteder, Gabriel Pabst, Tommaso Sconocchia, Angelika Schlacher, Lisa Auinger, Karl Kashofer, Christine Beham-Schmid, Slave Trajanoski, Claudia Waskow, Wolfgang Schöll, Heinz Sill, Armin Zebisch, Albert Wölfler, Daniel Thomas, and Andreas Reinisc