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  • 1
    Language: English
    In: The Journal of infectious diseases, 01 February 2010, Vol.201(3), pp.354-62
    Description: BACKGROUND. The nonstructural protein NS1 of influenza virus counteracts the interferon-mediated immune response of the host. By deleting the open reading frame of NS1, we have generated a novel type of influenza vaccine. We studied the safety and immunogenicity of an influenza strain lacking the NS1 gene (DeltaNS1-H1N1) in healthy volunteers. METHODS. Healthy seronegative adult volunteers were randomized to receive either a single intranasal dose of the DeltaNS1-H1N1 A/New Caledonia vaccine at 1 of 5 dose levels (6.4, 6.7, 7.0, 7.4, and 7.7 log(10) median tissue culture infective dose) (n = 36 recipients) or placebo (n = 12 recipients). RESULTS. Intranasal vaccination with the replication-deficient DeltaNS1-H1N1 vaccine was well tolerated. Rhinitis-like symptoms and headache were the most common adverse events identified during the 28-day observation period. Adverse events were similarly distributed between the treatment and placebo groups. Vaccine-specific local and serum antibodies were induced in a dose-dependent manner. In the highest dose group, vaccine-specific antibodies were detected in 10 of 12 volunteers. Importantly, the vaccine also induced neutralizing antibodies against heterologous drift variants. CONCLUSIONS. We show that vaccination with an influenza virus strain lacking the viral interferon antagonist NS1 induces statistically significant levels of strain-specific and cross-neutralizing antibodies despite the highly attenuated replication-deficient phenotype. Further studies are warranted to determine whether these results translate into protection from influenza virus infection. TRIAL REGISTRATION. ClinicalTrials.gov identifier: NCT00724997 .
    Keywords: Influenza A Virus, H1n1 Subtype -- Immunology ; Influenza Vaccines -- Immunology ; Influenza, Human -- Prevention & Control ; Vaccines, Attenuated -- Immunology ; Viral Nonstructural Proteins -- Genetics
    ISSN: 00221899
    E-ISSN: 1537-6613
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  • 2
    Language: English
    In: Cancer Research, 04/15/2010, Vol.70(8 Supplement), pp.4470-4470
    ISSN: 0008-5472
    E-ISSN: 1538-7445
    Source: CrossRef
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  • 3
    Language: English
    In: Cancer Research, 07/01/2017, Vol.77(13 Supplement), pp.2989-2989
    ISSN: 0008-5472
    E-ISSN: 1538-7445
    Source: CrossRef
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  • 4
    Language: German
    In: Wiener Medizinische Wochenschrift, 2013, Vol.163(13), pp.316-321
    Description: In Wien herrscht eine lange Tradition der Obduktion von Todesfällen in Krankenhäusern. Im Zeitraum von 1817 bis 2012 sind allein im Wiener Allgemeinen Krankenhaus mehr als 300.000 Obduktionen lückenlos dokumentiert. Aus fünf weiteren Gemeindekrankenhäusern mit Pathologien und einigen aufgelassenen Spitälern existieren Obduktionsbefunde zum Teil seit 1865. Die Befunde sind bis ins späte 19. Jahrhundert handschriftlich kurrent, danach in Lateinschrift und seit Einführung der Schreibmaschine in den 1920er Jahren als maschinenschriftlicher Durchschlag erhalten. Dem historischen Glücksfall der Erhaltung dieser Dokumente liegt einerseits die Tradition der Obduktionen seit Rokitansky, andererseits die Aufbewahrungsmöglichkeit in den Pathologisch anatomischen Sammlungen im Narrenturm wie auch im Wiener Stadt- und Landesarchiv und einzelnen Spitälern zugrunde. Ziel der vorliegenden Arbeit war es, eine Dokumentation der Aufbewahrungsorte zu erstellen, um die Befunde für verschiedene Zwecke auswertbar zu machen. So soll einerseits ein erleichtertes Wiederauffinden von Einzelbefunden möglich gemacht werden, andererseits eine Nutzung zu statistischen und anderen wissenschaftlichen Zwecken. Vienna has a long tradition of clinical autopsies. In the period from 1817 to 2012 there are over 300,000 autopsies documented in the Vienna General Hospital. From five other community hospitals with departments for pathology and some closed hospitals, autopsy reports exist since 1865. Until the nineteenth century the reports are written in Kurrent, then Latin script and since the 1920s they are stored as machine written copies. This incredible high number of preserved reports was only possible because of the tradition started by Rokitansky and the possibility of storing this large amount of records in the Pathologic anatomical collection in the Narrenturm, the Vienna Municipal Archives and various hospitals. The aim of this study was to create a documentary of the repositories of the autopsy records, to make the records available and easier accessible for different kinds of research. The autopsy records should be easier to find and access, be it for the use in statistics or other scientific projects.
    Keywords: Autopsy records ; History of pathology ; ­Documentation
    ISSN: 0043-5341
    E-ISSN: 1563-258X
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  • 5
    Language: German
    In: Wiener medizinische Wochenschrift (1946), July 2013, Vol.163(13-14), pp.316-21
    Description: Vienna has a long tradition of clinical autopsies. In the period from 1817 to 2012 there are over 300,000 autopsies documented in the Vienna General Hospital. From five other community hospitals with departments for pathology and some closed hospitals, autopsy reports exist since 1865. Until the nineteenth century the reports are written in Kurrent, then Latin script and since the 1920s they are stored as machine written copies. This incredible high number of preserved reports was only possible because of the tradition started by Rokitansky and the possibility of storing this large amount of records in the Pathologic anatomical collection in the Narrenturm, the Vienna Municipal Archives and various hospitals. The aim of this study was to create a documentary of the repositories of the autopsy records, to make the records available and easier accessible for different kinds of research. The autopsy records should be easier to find and access, be it for the use in statistics or other scientific projects.
    Keywords: Medical Records ; Archives -- History ; Autopsy -- History ; Documentation -- History ; Museums -- History ; Pathology -- History ; Schools, Medical -- History ; Universities -- History
    E-ISSN: 1563-258X
    Source: MEDLINE/PubMed (U.S. National Library of Medicine)
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  • 6
    Language: English
    In: Clinical cancer research : an official journal of the American Association for Cancer Research, 15 August 2011, Vol.17(16), pp.5322-32
    Description: In this study, we tested the antitumor activity of the dual phosphoinositide 3-kinase (PI3K)/mTOR inhibitor BEZ235 against gastric cancer in vitro and in vivo. Gastric cancer cell lines (N87, MKN45, and MKN28) were incubated with BEZ235 and assessed for cell viability, cell cycle, and PI3K/mTOR target inhibition. In vivo, athymic nude mice were inoculated with N87, MKN28, or MKN45 cells and treated daily with BEZ235. 3'-Deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) uptake was measured via small animal positron emission tomography (PET). In vitro, BEZ235 dose dependently decreased the cell viability of gastric cancer cell lines. The antiproliferative activity of BEZ235 was linked to a G(1) cell-cycle arrest. In vivo, BEZ235 treatment resulted in PI3K/mTOR target inhibition as shown by dephosphorylation of AKT and S6 protein in all xenograft models. However, BEZ235 treatment only inhibited tumor growth of N87 xenografts, whereas no antitumor effect was observed in the MKN28 and MKN45 xenograft models. Sensitivity to BEZ235 in vivo correlated with downregulation of the proliferation marker thymidine kinase 1. Accordingly, [(18)F]FLT uptake was only significantly reduced in the BEZ235-sensitive N87 xenograft model as measured by PET. In conclusion, in vivo sensitivity of gastric cancer xenografts to BEZ235 did not correlate with in vitro antiproliferative activity or in vivo PI3K/mTOR target inhibition by BEZ235. In contrast, [(18)F]FLT uptake was linked to BEZ235 in vivo sensitivity. Noninvasive [(18)F]FLT PET imaging might qualify as a novel marker for optimizing future clinical testing of dual PI3K/mTOR inhibitors.
    Keywords: Xenograft Model Antitumor Assays ; Imidazoles -- Pharmacology ; Phosphatidylinositol 3-Kinases -- Antagonists & Inhibitors ; Quinolines -- Pharmacology ; Stomach Neoplasms -- Drug Therapy ; Tor Serine-Threonine Kinases -- Antagonists & Inhibitors
    ISSN: 1078-0432
    E-ISSN: 15573265
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  • 7
    Language: English
    In: Urologia internationalis, 2017, Vol.99(3), pp.353-357
    Description: Pure testicular seminoma does not express alpha fetoprotein (AFP). However, seminoma patients with mildly elevated serum AFP levels are increasingly reported. As this finding may prompt unwarranted treatment measures, we reviewed our experience with AFP levels in seminoma. We retrospectively registered AFP levels in 254 consecutive seminoma patients, and in 196 male controls with non-malignant diseases. In those with elevated AFP levels, we re-examined the orchiectomy specimens histologically. We reviewed the clinical course and looked for hepatic disorders. Elevated AFP levels were found in 5 patients (1.97%, 95% CI 0.19-3.68) and in 4 controls (2.04%, 95% CI 0.06-4.02). The elevations were modest and kept elevated throughout the clinical course. No hepatic disorders were recorded. Histologically, pure seminoma was confirmed. Unspecific AFP elevations occur in about 2% of seminoma patients. Care-givers should be aware of this particular subgroup of seminoma patients to avoid unwarranted treatment burden.
    Keywords: Alpha Fetoprotein ; Biomarker ; Germ Cell Tumour ; Seminoma ; Testicular Neoplasm ; Neoplasms, Germ Cell and Embryonal -- Blood ; Seminoma -- Blood ; Testicular Neoplasms -- Blood ; Alpha-Fetoproteins -- Analysis
    ISSN: 00421138
    E-ISSN: 1423-0399
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  • 8
    Language: English
    In: Wiener Medizinische Wochenschrift, 2016, Vol.166(15), pp.453-461
    Description: The aim of this study was to compare in-hospital deaths in different hospital settings between 1850 and 2000 in Vienna. We reviewed 120 autopsy records for each of the selected years from the Clinical Institute of Pathology of the Medical University Vienna and two community hospitals. In 2000 the autopsy rate was 37.5 % at the community hospitals and 52.5 % at the university hospital. The mean age of those being dissected was significantly lower compared with those not being dissected in the community hospital. Infections were the leading cause of death during the nineteenth and early twentieth century, after 1950 the rate of cardiovascular diseases and cancer increased. In the year 2000 the majority of patients with an underlying malignant disease died because of cardiovascular disease. Causes of death vary between institutions. They should be reported as accurately as possible in order to create a cogent basis for central mortality statistics. Das Ziel dieser Untersuchung war der Vergleich von im Spital Verstorbener in verschiedenen Spitälern in Wien zwischen 1850 und 2000. Für die ausgewählten Jahre wurden jeweils 120 Befunde für jedes Spital gesichtet. Im Jahr 2000 lag die Obduktionsrate im Gemeindespital bei 37,5 %, in der Universitätsklinik bei 52,5 %. Im Jahr 2000 waren im Gemeindespital die Obduzierten signifikant jünger als jene, die nicht obduziert wurden. Infektionen waren die führende Todesursache während des 19. und frühen 20. Jahrhunderts. Nach 1950 stieg der Anteil der kardiovaskulären und malignen Erkrankungen an. Im Jahr 2000 verstarb die Mehrheit der Patienten mit einer zugrundeliegenden bösartigen Erkrankung an kardiovaskulären Todesursachen. Todesursachen und Patientenpopulationen unterscheiden sich signifikant zwischen Institutionen. Dementsprechend sollten Todesursachen so akkurat wie möglich registriert werden, um eine überzeugende Basis für eine zentralisierte Todesursachenstatistik zu bilden.
    Keywords: Autopsy ; Cause of death ; Pathology ; Medical history 19th century ; Medical history 20th century
    ISSN: 0043-5341
    E-ISSN: 1563-258X
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  • 9
    In: European Journal of Clinical Investigation, October 2014, Vol.44(10), pp.958-964
    Description: To purchase or authenticate to the full-text of this article, please visit this link: http://onlinelibrary.wiley.com/doi/10.1111/eci.12329/abstract Byline: Thorsten Fuereder, Judith Stift, Irene Kuehrer, Nadja Stranzl, Doris Hoeflmayer, Gabriela Kornek, Werner Scheithauer Keywords: ERCC1; erlotinib; GEMOX ; pancreatic adenocarcinoma Abstract Introduction There are no data about the efficacy of gemcitabine in combination with oxaliplatin (GEMOX) and erlotinib for the treatment of metastatic pancreatic cancer (mPC). Thus, we performed this retrospective analysis in mPC patients to investigate the activity and safety of GEMOX plus erlotinib and correlated the benefit with ERCC1 expression, a potential biomarker for treatment response. Patients and methods Patients with untreated mPC receiving off-protocol GEMOX plus erlotinib were included. Data collection included baseline demographic, response and toxicity data as well as PFS and OS. Additionally, immunohistochemistry was performed to stain for ERCC1 expression. Results A total of 51 patients were included. The median age was 62 years and the median ECOG performance score was 1 (range, 0-1). Objective response or disease stabilization was achieved in 54% of the patients. The median PFS was 4ae4 months (95% CI 4ae4-5ae4) and median OS was 8ae5 months (95% CI 6ae1-10ae9). The 27 patients, who benefited from this regimen, had a median PFS of 6ae7, a median OS of 11ae2 months and an overexpression of ERCC1 (histoscore 10, P [less than or equal to] 0ae05) compared to nonresponders (histoscore 7ae2). Myelosuppression was the most frequent side effect. The most common severe nonhematological toxicities were diarrhoea and skin toxicity in six (12%) patients each. Conclusions These data suggest that the combination of GEMOX plus erlotinib is safe and active in about half of the patients. Patients, who had a higher ERCC1 staining pattern, benefited most from this therapy. Prospective biomarker studies are warranted to confirm these findings.
    Keywords: 1 ; Erlotinib ; Gemox ; Pancreatic Adenocarcinoma
    ISSN: 0014-2972
    E-ISSN: 1365-2362
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  • 10
    In: Case Reports in Oncological Medicine, 2017, Vol.2017, 5 pages
    Description: Somatic type malignancy (STM) occurs in 2% of all germ cell tumours (GCTs). The prognosis is unfavourable and the origin is poorly understood. Pathogenetic hypotheses involve direct transformation of teratoma, origin from totipotent cancer cells, or derivation from yolk sac tumour elements.A 31-year-old patient was cured from testicular seminoma clinical stage IIc by orchiectomy and cisplatin-based chemotherapy. Nine years later, he experienced a late relapse with a mass sized  cm located at the former metastatic site. As no remission occurred after chemotherapy with three cycles of cisplatin, ifosfamide and etoposide, the mass was surgically resected. Histologically, the specimen consisted of neurofibroma with areas of malignant peripheral nerve sheath tumour and spots with mature bone formation. FISH analysis disclosed isochromosome 12p in the majority of evaluated cells suggesting somatic type malignancy (STM) of GCT. The patient is well 1 year after surgery.The pathogenesis of this STM remains enigmatic. The origin from GCT was evidenced by documentation of isochromosome 12p. Unrecognized teratomatous elements in the primary and totipotent cancer cells surviving the first chemotherapy could be hypothesized to represent the origin. STM developing from seminoma cells would be another novel hypothesis.
    Keywords: Medicine;
    ISSN: 2090-6706
    E-ISSN: 2090-6714
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