156 research outputs found
Postmortem diagnostics using MSCT and MRI of a lethal streptococcus group A infection at infancy: a case report.
No full textPostmortem cross-sectional imaging using multislice computed tomography (MSCT) and magnetic resonance imaging (MRI) was considered as a base for a minimal invasive postmortem investigation in forensic medicine such as within the Virtopsy approach. We present the case of a 3-year-old girl with a lethal streptococcus group A infection and the findings of postmortem imaging in this kind of natural death. Postmortem MSCT and MRI revealed an edematous occlusion of the larynx at the level of the vocal cords, severe pneumonia with atelectatic parts of both upper lobes and complete atelectasis of both lower lobes, purulent fluid-filled right main bronchus, enlargement of cervical lymph nodes and pharyngeal tonsils, and additionally, a remaining glossopharyngeal cyst as well as an ureter fissus of the right kidney. All relevant autopsy findings could be obtained and visualized by postmortem imaging and confirmed by histological and microbiological investigations supporting the idea of a minimal invasive autopsy technique
Chemokine microenvironment in primary central nervous system lymphoma
No full textPrimary central nervous system lymphomas (PCNSL) are aggressive extranodal malignancies confined to the central nervous system (CNS), mostly of diffuse large B cell histotype. Despite improved understanding of the malignant B cells, little is known on the tumor microenvironment and on the response of the adaptive immunity against PCNSL. The majority of B-cell lymphomas, including PCNSL originate from germinal center (GC) B cells. The GC is the main source of memory B cells and plasma cell generation, which produce high affinity antibodies and are necessary to protect us against invading microorganisms. However, the beneficial role of GC B cells in immunity is counterbalanced by their detrimental role in lymphomagenesis. Germinal center B cells express a distinct set of chemokine receptors, which regulate their migration and positioning during and after germinal center reaction. Similar to centrocytes and centroblasts, malignant B cells derived from germinal centers can retain a particular set of chemokine receptors, which allows them to respond to their cognate ligands expressed in the microenvironment. Therefore investigation of lymphocyte chemoattractants in secondary lymphoid organs as well as in extranodal lymphomas does not only improve our understanding of B cell trafficking within secondary lymphoid organs, but also helps us understanding tumor cell distribution and dissemination of malignant B cells as well as tumor infiltrating lymphocytes. Gene expression analysis has previously shown, that malignant B cells in PCNSL resemble late germinal center B cells and express classical B cell chemokine receptors. This work focuses on the chemokine microenvironment and the potential role of bystander cells in PCNSL and their effects on malignant B cells as well as tumor infiltrating lymphocytes. The project includes four major sections: 1. Analysis of the expression of B cell attracting chemokines under normal and inflammatory conditions in human secondary lymphoid organs. 2. Analysis of T and B cell attracting chemokines in extranodal CNS lymphomas, 3. Analysis of type, density and localization of tumor infiltrating lymphocytes in PCNSL, 4. Analysis of the effect of coexpressed chemokines in PCNSL on the migratory responses of tumor-infiltrating lymphocytes and malignant B cells. We show by immunhistochemistry and in-situ hybridization, that there is a specific expression pattern of homeostatically expressed chemokines CXCL12, CXCL13 and CCL21 in normal, non-inflamed human secondary lymphoid organs. Under inflammatory conditions, the expression pattern of macrophage- derived CXCL12 and follicular dendritic cell- derived CXCL13 within the germinal center changes significantly. Within the germinal center, macrophage-derived CXCL12 and follicular dendritic cell-derived CXCL13 build a meshwork in which germinal center B cells reside. While CXCL13 shows a clear gradient between the dark and the light zone of the germinal center in human secondary lymphoid tissue, we could not detect a clear gradient for CXCL12 between the two zones. Analysis of CXCL12 and CXCL13 in primary central nervous system lymphoma showed an expression pattern similar to the one in germinal centers of secondary lymphoid organs. In addition, we identified a fraction of CXCL13-expressing lymphocytes in PCNSL. CXCL13-expression is a hallmark of germinal center T cells known as follicular T helper cells (TFH), which provide help to germinal center B cells. Yet, the majority of tumor infiltrating lymphocytes in PCNSL are CD8+ T cells, which show Granzyme B activity and vigorous proliferation. Tumor infiltrating CD8+ T cells show a higher frequency in the perivascular areas of small and intermediate vessels in PCNSL. They accumulate in areas with high expression of the inflammatory chemokine CXCL9. Perivascular CXCL9 is upregulated by perivascular macrophages and pericytes under inflammatory conditions in the CNS, indicating an important role for pericytes and perivascular macrophages in the recruitment of tumor infiltrating lymphocytes. Moreover, CXCL9 and CXCL12 are coexpressed on the tumor vasculature within PCNSL and can form heterocomplexes. Our in-vitro experiments show, that in the presence of CXCL9, CXCL12-induced migration is enhanced not only on CXCR4+/CXCR3+/CD8+ T cells but also on CXCR4+/CXCR3- malignant B cells. Our findings indicate, that malignant B cells in PCNSL may encounter a germinal-center like chemokine environment, which traps malignant B cells within the CNS. In addition, our results reveal the presence of a strong chemoattractant stimulus in the perivascular microenvironment, which might serve as regulator for the recruitment of tumor infiltrating lymphocytes and for the angiocentric positioning of malignant B cells in the perivascular cuff
Postmortem non-invasive virtual autopsy: death by hanging in a car.
No full textA body was found behind a car with a noose tied around its neck, the other end of the rope tied to a tree. Apparently the man committed suicide by driving away with the noose tied around his neck and was dragged out of the car through the open hatchback. postmortem multislice-computed tomography (MSCT) and magnetic resonance imaging (MRI) indicated that the cause of death was cerebral hypoxia due to classic strangulation by hanging, and not due to a brainstem lesion because of a hang-man fracture as would be expected in such a dynamic situation. Furthermore, the MRI displayed intramuscular haemorrhage, bleeding into the clavicular insertions of the sternocleidomastoid muscles and subcutaneous neck tissue. We conclude that MSCT and MRI are useful instruments with an increased value compared with 2D radiographs to augment the external findings of bodies when an autopsy is refused. But further postmortem research and comparing validation is needed
Population-based outcome analysis of diffuse large B-cell lymphoma in people living with HIV infection and competent individuals.
No full textThe prognostic factors and outcome of 58 acquired immunodeficiency syndrome-related diffuse large B-cell lymphoma (AR-DLBCL) patients from the Swiss HIV Cohort Study, diagnosed from 2004 to 2011, were compared with those of 326 immunocompetent (IC)-DLBCL from the Hematology Division of the Amedeo Avogadro University (Italy) and the Oncology Institute of Southern Switzerland. Median follow-up was 6 years; 5-year overall survival (OS) was 68% (95% CI: 63%-73%) in IC-DLBCL and 63% (95% CI: 49%-75%) in AR-DLBCL (P = .220). The acquired immunodeficiency syndrome-related lymphoma international prognostic index predicted OS in AR-DLBCL. Among 148 patients younger than 61 years (40 AR-DLBCL and 108 IC-DLBCL) treated with RCHOP/RCHOP-like regimens, 20 IC-DLBCL and 9 AR-DLBCL patients died and OS was not significantly different. A higher proportion of early deaths occurred in the AR-DLBCL: indeed, 1-year OS was 94% (95% CI: 87%-97%) in IC-DLBCL and 82% (95% CI: 66%-91%) in AR-DLBCL patients. After rituximab and active antiretroviral therapy introduction, AR-DLBCL and IC-DLBCL patients treated with curative intent have similar long-term survival
Virtopsy in der Unfallrekonstruktion
No full textMit der Virtopsy hat das Institut für Rechtmedizin der Universität Bern unter Prof. Dr. med. R. Dirnhofer und Prof. Dr. med. M. Thali die Rechtsmedizin über die ganze Welt revolutioniert. Obwohl einzelne Techniken, aus dem klinischen Medizinalltag stammend, bereits zu früherer Zeit im einen oder andere Autopsie-Saal bereits zur Anwendung kamen, waren es die Berner Rechtsmediziner, Radiologen und Ingenieure, welche diese kombinierten. Unter dem Begriff Virtopsy vereint sich die Nutzung von medizinischen bildgebenden Verfahren mit dem Erfassen der Körperoberfläche mittels 3D-Oberflächenscanning. Dadurch hat Virtopsy, nebst den rekonstruktiven Möglichkeiten, ein immenses Potential für die Dokumentation sowohl vom Verstorbenen als auch von Verletzungen von Lebenden. Gerade mittels der räumlichen Darstellung von inneren Verletzungen und Frakturen können diese für den medizinischen Laien optimal dargestellt und verständlich gemacht werden.
Bei der Klärung von Verkehrsunfällen, insbesondere bei Kollisionen von Motorfahrzeugen mit Fussgängern oder Zweiradfahrern - gegenüber welchen der Mensch besonders exponiert und verletzlich ist - aber auch zur Klärung von Verletzungen an Fahrzeuginsassen, zeigen sich die rekonstruktiven Möglichkeiten von Virtopsy.
Dabei gilt zu beachten, dass die 3D-Dokumentation mittels den erwähnten Verfahren eine Akquisition von digitalen Daten, nicht automatisch eine vollständige Auswertung zur Folge haben muss. Trotzdem zeigt sich, dass viele offene Fragen erst im Nachhinein auftreten, wenn die Befunde und Spuren nicht mehr zugänglich sind. Die mittels Virtopsy erhobenen digitalen Daten lassen sich jedoch zu jedem Zeitpunkt neu befunden oder weiter bearbeiten und können auch in Zukunft zur Klärung eines Unfallereignisses beitragen
Theoretical and experimental investigations of thin asphalt overlays on continuously reinforced concrete pavements
No full textIn der Arbeit wird eine Kompositbauweise für höchstbelastete Autobahnen vorgestellt. Anhand von Spannungsberechnungen an durchgehend bewehrten Betonfahrbahndecken erfolgt eine Prognose der Rissabstände für unterschiedliche Temperatureinwirkungen und Betonfestigkeiten. Ferner wird der Verbund von dünnen Asphaltdeckschichten auf Betonfahrbahndecken mithilfe eines neu entwickelten dynamischen Abscherversuchs untersucht. Zum Abschluss wird ein Konzept für die Realisierung des untersuchten Straßenoberbaus vorgestellt.This work presents a composite pavement for highly stressed highways. Based on stress analysis for continuously reinforced concrete pavements there is shown the prediction of crack spacing caused by different temperatures and different concrete strengths. Furthermore, some investigations were made to prove the bond between the thin asphalt overlays and the concrete pavement by the use of a newly developed dynamic shear test. Finally, a concept for the realization of the composite superstructure is presented
Histiocytic and dendritic cell neoplasms: what have we learnt by studying 67 cases
No full textTumors derived from histiocytic and dendritic cells encompass a large and heterogeneous group of neoplastic and reactive conditions, and their diagnosis is challenging both for pathologists and clinicians. Diagnosis is based on morphological and phenotypical findings, but hybrid features are not uncommon. Furthermore, recent studies uncovered the molecular mechanisms driving some of these tumors, improving diagnostic adequacy, and providing the basis for effective therapeutic breakthroughs.Sixty-seven cases were submitted to the accessory cell and histiocytic neoplasms session at the European Association of Haematopathology/Society for Hematopathology workshop 2016 held in Basel, Switzerland. The cases included histiocytic sarcomas (HS), Langerhans cell tumors (LCT), Erdheim-Chester disease, interdigitating dendritic cell sarcomas (IDCS), indeterminate dendritic cell tumors (IND-DCT), follicular dendritic cell sarcomas, and blastic plasmacytoid dendritic cell neoplasms. Rosai-Dorfman disease and, more rare, conditions such as ALK-positive histiocytosis were also submitted. These cases illustrated classical and unexpected features at morphological, phenotypical, and molecular levels, providing a valuable compendium for pathologists confronting with these tumors.The paper summarizes the most notable features of every single group of diseases, with comments about the most challenging issues, in the attempt to provide practical indications for their recognition
Postmortem imaging-guided biopsy as an adjuvant to minimally invasive autopsy with CT and postmortem angiography : a feasibility study
No full textAlthough postmortem CT suffices for diagnosing most forms of traumatic death, the examination of natural death is, to date, very difficult and error prone. The introduction of postmortem angiography has led to improved radiologic diagnoses of natural deaths. Nevertheless, histologic changes to tissues, an important aspect in traditional examination procedures, remain obscure even with CT and CT angiography. For this reason, we examined the accuracy of a minimally invasive procedure (i.e., CT angiography combined with biopsy) in diagnosing major findings and the cause of death in natural deaths
Expression of minichromosome maintenance protein 2 as a marker for proliferation and prognosis in diffuse large B-cell lymphoma: a tissue microarray and clinico-pathological analysis
No full textAbstract Background Minichromosome maintenance (MCM) proteins are essential for the initiation of DNA replication and have been found to be relevant markers for prognosis in a variety of tumours. The aim of this study was to assess the proliferative activity of diffuse large B-cell lymphoma (DLBCL) in tissue microarray (TMA) using one of the minichromosome maintenance proteins (Mcm2) and to explore its potential value to predict prognosis. Methods Immunohistochemistry for Mcm2 was performed on TMAs constructed from 302 cases of DLBCL. A monoclonal mouse antibody was used after heat induced antigen retrieval. Mcm2 expression was scored quantitatively. Positivity for Mcm2 was defined as presence of nuclear expression of Mcm2 in greater than or equal to 40 % of tumour cells. A statistical analysis was carried out of the association of Mcm2 and the clinico-pathological characteristics. Results Mcm2 expression was clearly evident in the nuclei of proliferating non-neoplastic cells and tumour cells. Positivity for Mcm2 was found in 46% (98/211) of analysable cases. A significant correlation existed between Mcm2 expression and presence of bulky disease (p = 0.003). Poor disease specific survival was observed in patients with DLBCL positive for Mcm2 expression in the univariate analysis (p = 0.0424). Conclusion Mcm2 expression can be used to assess tumour proliferation and may be useful as an additional prognostic marker to refine the prediction of outcome in DLBCL.</p
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