Publications

959 Publications visible to you, out of a total of 959

Abstract (Expand)

OBJECTIVE To determine the prevalence and mortality of ICU patients with severe sepsis in Germany, with consideration of hospital size. DESIGN Prospective, observational, cross-sectional 1-dayday point-prevalence study. SETTING 454 ICUs from a representative nationwide sample of 310 hospitals stratified by size. Data were collected via 1-day on-site audits by trained external study physicians. Visits were randomly distributed over 1 year (2003). PATIENTS Inflammatory response of all ICU patients was assessed using the ACCP/SCCM consensus conference criteria. Patients with severe sepsis were followed up after 3 months for hospital mortality and length of ICU stay. MEASUREMENTS AND RESULTS Main outcome measures were prevalence and mortality. A total of 3,877 patients were screened. Prevalence was 12.4% (95% CI, 10.9-13.8%) for sepsis and 11.0% (95% CI, 9.7-12.2%) for severe sepsis including septic shock. The ICU and hospital mortality of patients with severe sepsis was 48.4 and 55.2%, respectively, without significant differences between hospital size. Prevalence and mean length of ICU stay of patients with severe sepsis were significantly higher in larger hospitals and universities (\textless/= 200 beds: 6% and 11.5 days, universities: 19% and 19.2 days, respectively). CONCLUSIONS The expected number of newly diagnosed cases with severe sepsis in Germany amounts to 76-110 per 100,000 adult inhabitants. To allow better comparison between countries, future epidemiological studies should use standardized study methodologies with respect to sepsis definitions, hospital size, and daily and monthly variability.

Authors: Christoph Engel, Frank M. Brunkhorst, Hans-Georg Bone, Reinhard Brunkhorst, Herwig Gerlach, Stefan Grond, Matthias Gruendling, Guenter Huhle, Ulrich Jaschinski, Stefan John, Konstantin Mayer, Michael Oppert, Derk Olthoff, Michael Quintel, Max Ragaller, Rolf Rossaint, Frank Stuber, Norbert Weiler, Tobias Welte, Holger Bogatsch, Christiane Hartog, Markus Loeffler, Konrad Reinhart

Date Published: 23rd Mar 2007

Publication Type: Journal article

Human Diseases: disease by infectious agent

Abstract (Expand)

DNA genotyping is important for epidemiological and clinical studies and diagnosis for individuals. Genotyping error can strongly influence the outcome of such investigations. One possible reason for genotyping error is additional DNA sequence variation, which can lead to allelic dropout. Based on a published study where allelic dropout occurred in genotyping the cholesteryl ester transfer protein TaqIB polymorphism by a TaqMan-based method, we investigated the susceptibility of the single-base extension (SBE)-based GenoSNIP method to additional sequence variation at the primer attachment site. SBE genotyping was applied to 147 patient samples with known alleles and to synthetic SBE templates. Variables were positions of nucleotide mismatches, yield of SBE reactions, primer design, and ratio of alleles in the template. No allelic dropout occurred when genotyping the TaqIB polymorphism regardless of the reported nucleotide mismatch. Yields of SBE assays critical for allelic dropout were decreased in the presence of the reported nucleotide mismatch depending on SBE assay design. In a systematic mutation scan, only the position immediately adjacent to the polymorphism caused allelic dropout under standard conditions. Depending on SBE assay design, changes in allelic ratio due to a nucleotide mismatch were similar in appearance to changes due to sample mixture or copy number variation. In conclusion, we found the SBE genotyping assays to be relatively robust against interfering DNA variations. The importance of appropriate design and validation of assays, especially in regard to critical yields and potentially interfering nucleotide mismatches, should be emphasized particularly in clinical settings. Care should be taken when interpreting observed changes in the allelic ratio, which could be caused by nucleotide mismatches, sample mixtures, or copy number variation.

Authors: Holger Kirsten, Daniel Teupser, Jana Weissfuss, Grit Wolfram, Frank Emmrich, Peter Ahnert

Date Published: 20th Mar 2007

Publication Type: Journal article

Abstract (Expand)

Esthesioneuroblastoma is a malignant neuroectodermal tumor originating from olfactory epithelial cells in the nasal vault. Due to the rarity of this tumor entity, cytogenetic data are very limited. Therefore, we performed comprehensive cytogenetic analyses of an esthesioneuroblastoma, Hyam’s grade III-IV, using trypsin-Giemsa staining (GTG banding), multicolor fluorescence in situ hybridization (M-FISH), and locus-specific FISH complemented by molecular karyotyping using high-density single nucleotide polymorphism arrays. GTG banding of 25 metaphases revealed 54 structural intrachromosomal aberrations, predominantly located on 2q, 6q, 21q, and 22q, which were confirmed by FISH analysis. Interestingly, we found two novel, so far not described deletions, del(2)(q37) and del(21)(q22). Using GTG banding, locus-specific FISH, and M-FISH, we detected numeric changes of chromosomes 5, 17, 19, and 22, as well as trisomy 8 at low frequency. Applying SNP array karyotyping, we confirmed the chromosomal aberrations del(2)(q37.3), del(3)(q27.2), del(10)(q26.11), chromosomal imbalance on 17q, del(21)(q22), and revealed a number of so far unknown aberrations (gain of 2q14.3, 13q33.3, and 13q34). While the cytogenetically revealed low frequency mosaic del(6)(q22q24) was not visible using SNP array karyotyping, some of the smaller imbalances (SNP array data) could not have been detected by classic cytogenetic analysis. Therefore, our study supports the usefulness of applying complementary methods for cytogenetic analysis.

Authors: Heidrun Holland, Ronald Koschny, Wolfgang Krupp, Jürgen Meixensberger, Manfred Bauer, Holger Kirsten, Peter Ahnert

Date Published: 1st Mar 2007

Publication Type: Journal article

Abstract

Not specified

Authors: Anke Tönjes, Markus Scholz, Mathias Fasshauer, Jürgen Kratzsch, Fauci Rassoul, Michael Stumvoll, Matthias Blüher

Date Published: 27th Feb 2007

Publication Type: Journal article

Abstract (Expand)

BACKGROUND: Malignant growth and invasiveness of cancers is a function of both intratumoral and stromal factors. The accessibility to nutrients, oxygen and growth factors, the stromal composition, and the interference with the immune system all shape the tumor invasion front. A recent study has shown a prognostic difference with respect to different invasion patterns analyzed on histological specimens of cervical cancers. The present study analyzes the spatial organization of a cervical cancer and the relation of the tumor invasion front and the infiltration with CD3(+) T-cells. METHODS: From a cervical squamous cell carcinoma specimen, 84 serial sections were performed and three interleaving series were stained with hematoxylin/eosin and immunohistochemistry directed against the cervical carcinoma biomarker p16(INK4a) and the T-cell marker CD3. Sections were passed through an image processing chain to obtain a reconstructed and segmented tissue volume. For local tumor invasion front analysis the mean curvature was used, which in turn was related to the respective local minimum tumor to T-cell distance as well to a T-cell originated diffusing substance's concentration at the tumor surface. RESULTS: Spatial models of the tumor tissue and the infiltrating T-cells were computed. The overall discrete compactness of the tumor invasion front was 0.89, corresponding to a pathological assessment of diffuse infiltration. The comparison of the tumor invasion front with the density of T-cell infiltration revealed an increased smoothening in regions with high T-cell infiltration. CONCLUSIONS: We could demonstrate the spatial organization of a cervical cancer and model the interaction between infiltrating T-cells with the tumor invasion front shape. Increased smoothening in regions with high T-cell infiltration suggests that T-cells may have an influence on the shaping of the tumor invasion front, e.g., by attacking tumor cells displaying specific antigens. The applied technique allows visualization of the spatial organization of tissues and could be extended to analyze multiple stains on alternating sections.

Authors: N. Wentzensen, U. D. Braumann, J. Einenkel, L. C. Horn, M. von Knebel Doeberitz, M. Loffler, J. P. Kuska

Date Published: 7th Feb 2007

Publication Type: Not specified

Human Diseases: cervical cancer

Abstract (Expand)

The Interleukin 10 (IL-10) gene is highly polymorphic, and the IL-10(-1087AG) (rs1800896) gene variation is the only so far studied intensively in association with certain diseases. Conflicting data have been published about an association of IL-10(-1087AG) gene variation with lower rates of complete remission and lower overall survival (OS) in patients with diffuse large B-cell lymphoma. To further investigate this in malignant lymphoma, we established the IL-10 genotypes in patients from the NHL-B1/ B2 studies from the German High-Grade Non-Hodgkin's Lymphoma Study Group. In our study, allele frequencies of lymphoma patients are comparable as in healthy controls. No increase of IL-10(-1087G) alleles was found. In addition we did not find any difference in OS or event-free survival between patients with IL-10(-1087AA) and the other genotypes. Comparable results were obtained for the IL-10 loci at -3538 (A/T), -1354 (A/G), -824 (C/T) and -597 (A/C) (rs1800890, rs1800893, rs1800871 and rs1800872).

Authors: D. Kube, T. D. Hua, M. Kloss, B. Kulle, J. Brockmoller, L. Wojnowski, M. Loffler, M. Pfreundschuh, L. Trumper

Date Published: 12th Jan 2007

Publication Type: Not specified

Human Diseases: non-Hodgkin lymphoma

Abstract

Not specified

Authors: J. Einenkel, W. Steller, U. D. Braumann, L. C. Horn, C. Krafft

Date Published: 11th Jan 2007

Publication Type: Not specified

Human Diseases: cervical cancer

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