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468 Publications visible to you, out of a total of 468
MicroRNA signatures characterize diffuse large B-cell lymphomas and follicular lymphomas.
GLA - German Lymphoma Alliance

Abstract (Expand)

MicroRNAs (miRNA, miR) are negative regulators of gene expression that play an important role in diverse biological processes such as development, cell growth, apoptosis and haematopoiesis, suggesting … their association with cancer. Here we analysed the expression signatures of 157 miRNAs in 58 diffuse large B-cell lymphoma (DLBCL), 46 follicular lymphoma (FL) and seven non-neoplastic lymph nodes (LN). Comparison of the possible combinations of DLBCL-, FL- and LN resulted in specific DLBCL- and FL-signatures, which include miRNAs with previously published function in haematopoiesis (MIRN150 and MIRN155) or tumour development (MIRN210, MIRN10A, MIRN17-5P and MIRN145). As compared to LN, some miRNAs are differentially regulated in both lymphoma types (MIRN155, MIRN210, MIRN106A, MIRN149 and MIRN139). Conversely, some miRNAs show lymphoma-specific aberrant expression, such as MIRN9/9*, MIRN301, MIRN338 and MIRN213 in FL and MIRN150, MIRN17-5P, MIRN145, MIRN328 and others in DLBCL. A classification tree was computed using four miRNAs (MIRN330, MIRN17-5P, MIRN106a and MIRN210) to correctly identify 98% of all 111 cases that were analysed in this study. Finally, eight miRNAs were found to correlate with event-free and overall survival in DLBCL including known tumour suppressors (MIRN21, MIRN127 and MIRN34a) and oncogenes (MIRN195 and MIRNLET7G).

Authors: A. Roehle, K. P. Hoefig, D. Repsilber, C. Thorns, M. Ziepert, K. O. Wesche, M. Thiere, M. Loeffler, W. Klapper, M. Pfreundschuh, A. Matolcsy, H. W. Bernd, L. Reiniger, H. Merz, A. C. Feller

Date Published: 10th Jun 2008

Publication Type: Not specified

Human Diseases: diffuse large B-cell lymphoma

Common breast cancer-predisposition alleles are associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers
GC-HBOC - German Consortium for Hereditary Breast and Ovarian Cancer

Abstract (Expand)

Germline mutations in BRCA1 and BRCA2 confer high risks of breast cancer. However, evidence suggests that these risks are modified by other genetic or environmental factors that cluster in families. A … recent genome-wide association study has shown that common alleles at single nucleotide polymorphisms (SNPs) in FGFR2 (rs2981582), TNRC9 (rs3803662), and MAP3K1 (rs889312) are associated with increased breast cancer risks in the general population. To investigate whether these loci are also associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers, we genotyped these SNPs in a sample of 10,358 mutation carriers from 23 studies. The minor alleles of SNP rs2981582 and rs889312 were each associated with increased breast cancer risk in BRCA2 mutation carriers (per-allele hazard ratio [HR] = 1.32, 95% CI: 1.20-1.45, p(trend) = 1.7 x 10(-8) and HR = 1.12, 95% CI: 1.02-1.24, p(trend) = 0.02) but not in BRCA1 carriers. rs3803662 was associated with increased breast cancer risk in both BRCA1 and BRCA2 mutation carriers (per-allele HR = 1.13, 95% CI: 1.06-1.20, p(trend) = 5 x 10(-5) in BRCA1 and BRCA2 combined). These loci appear to interact multiplicatively on breast cancer risk in BRCA2 mutation carriers. The differences in the effects of the FGFR2 and MAP3K1 SNPs between BRCA1 and BRCA2 carriers point to differences in the biology of BRCA1 and BRCA2 breast cancer tumors and confirm the distinct nature of breast cancer in BRCA1 mutation carriers.

Authors: Antonis C. Antoniou, Amanda B. Spurdle, Olga M. Sinilnikova, Sue Healey, Karen A. Pooley, Rita K. Schmutzler, Beatrix Versmold, Christoph Engel, Alfons Meindl, Norbert Arnold, Wera Hofmann, Christian Sutter, Dieter Niederacher, Helmut Deissler, Trinidad Caldes, Kati Kämpjärvi, Heli Nevanlinna, Jacques Simard, Jonathan Beesley, Xiaoqing Chen, Susan L. Neuhausen, Timothy R. Rebbeck, Theresa Wagner, Henry T. Lynch, Claudine Isaacs, Jeffrey Weitzel, Patricia A. Ganz, Mary B. Daly, Gail Tomlinson, Olufunmilayo I. Olopade, Joanne L. Blum, Fergus J. Couch, Paolo Peterlongo, Siranoush Manoukian, Monica Barile, Paolo Radice, Csilla I. Szabo, Lutecia H. Mateus Pereira, Mark H. Greene, Gad Rennert, Flavio Lejbkowicz, Ofra Barnett-Griness, Irene L. Andrulis, Hilmi Ozcelik, Anne-Marie Gerdes, Maria A. Caligo, Yael Laitman, Bella Kaufman, Roni Milgrom, Eitan Friedman, Susan M. Domchek, Katherine L. Nathanson, Ana Osorio, Gemma Llort, Roger L. Milne, Javier Benítez, Ute Hamann, Frans B. L. Hogervorst, Peggy Manders, Marjolijn J. L. Ligtenberg, Ans M. W. van den Ouweland, Susan Peock, Margaret Cook, Radka Platte, D. Gareth Evans, Rosalind Eeles, Gabriella Pichert, Carol Chu, Diana Eccles, Rosemarie Davidson, Fiona Douglas, Andrew K. Godwin, Laure Barjhoux, Sylvie Mazoyer, Hagay Sobol, Violaine Bourdon, François Eisinger, Agnès Chompret, Corinne Capoulade, Brigitte Bressac-de Paillerets, Gilbert M. Lenoir, Marion Gauthier-Villars, Claude Houdayer, Dominique Stoppa-Lyonnet, Georgia Chenevix-Trench, Douglas F. Easton

Date Published: 1st Apr 2008

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60).
GLA - German Lymphoma Alliance

Abstract (Expand)

BACKGROUND: Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) is used to treat patients with non-Hodgkin lymphoma. Interval decrease from 3 weeks of treatment (CHOP-21) to 2 weeks … (CHOP-14), and addition of rituximab to CHOP-21 (R-CHOP-21) has been shown to improve outcome in elderly patients with diffuse large B-cell lymphoma (DLBCL). This randomised trial assessed whether six or eight cycles of R-CHOP-14 can improve outcome of these patients compared with six or eight cycles of CHOP-14. METHODS: 1222 elderly patients (aged 61-80 years) were randomly assigned to six or eight cycles of CHOP-14 with or without rituximab. Radiotherapy was planned to sites of initial bulky disease with or without extranodal involvement. The primary endpoint was event-free survival; secondary endpoints were response, progression during treatment, progression-free survival, overall survival, and frequency of toxic effects. Analyses were done by intention to treat. The trial is registered on National Cancer Institute website, number NCT00052936 and as EU-20243. FINDINGS: 3-year event-free survival was 47.2% after six cycles of CHOP-14 (95% CI 41.2-53.3), 53.0% (47.0-59.1) after eight cycles of CHOP-14, 66.5% (60.9-72.0) after six cycles of R-CHOP-14, and 63.1% (57.4-68.8) after eight cycles of R-CHOP-14. Compared with six cycles of CHOP-14, the improvement in 3-year event-free survival was 5.8% (-2.8-14.4) for eight cycles of CHOP-14, 19.3% (11.1-27.5) for six cycles of R-CHOP-14, and 15.9% (7.6-24.2) for eight cycles of R-CHOP-14. 3-year overall survival was 67.7% (62.0-73.5) for six cycles of CHOP-14, 66.0% (60.1-71.9) for eight cycles of CHOP-14, 78.1% (73.2-83.0) for six cycles of R-CHOP-14, and 72.5% (67.1-77.9) for eight cycles of R-CHOP-14. Compared with treatment with six cycles of CHOP-14, overall survival improved by -1.7% (-10.0-6.6) after eight cycles of CHOP-14, 10.4% (2.8-18.0) after six cycles of R-CHOP-14, and 4.8% (-3.1-12.7) after eight cycles of R-CHOP-14. In a multivariate analysis that used six cycles of CHOP-14 without rituximab as the reference, and adjusting for known prognostic factors, all three intensified regimens improved 3-year event-free survival (eight cycles of CHOP-14: RR [relative risk] 0.76 [0.60-0.95], p=0.0172; six cycles of R-CHOP-14: RR 0.51 [0.40-0.65], p<0.0001; eight cycles of R-CHOP-14: RR 0.54 [0.43-0.69], p<0.0001). Progression-free survival improved after six cycles of R-CHOP-14 (RR 0.50 [0.38-0.67], p<0.0001), and eight cycles of R-CHOP-14 (RR 0.59 [0.45-0.77], p=0.0001). Overall survival improved only after six cycles of R-CHOP-14 (RR 0.63 [0.46-0.85], p=0.0031). In patients with a partial response after four cycles of chemotherapy, eight cycles were not better than six cycles. INTERPRETATION: Six cycles of R-CHOP-14 significantly improved event-free, progression-free, and overall survival over six cycles of CHOP-14 treatment. Response-adapted addition of chemotherapy beyond six cycles, though widely practiced, is not justified. Of the four regimens assessed in this study, six cycles of R-CHOP-14 is the preferred treatment for elderly patients, with which other approaches should be compared.

Authors: M. Pfreundschuh, J. Schubert, M. Ziepert, R. Schmits, M. Mohren, E. Lengfelder, M. Reiser, C. Nickenig, M. Clemens, N. Peter, C. Bokemeyer, H. Eimermacher, A. Ho, M. Hoffmann, R. Mertelsmann, L. Trumper, L. Balleisen, R. Liersch, B. Metzner, F. Hartmann, B. Glass, V. Poeschel, N. Schmitz, C. Ruebe, A. C. Feller, M. Loeffler

Date Published: 30th Jan 2008

Publication Type: Not specified

Human Diseases: non-Hodgkin lymphoma, B-cell lymphoma

Current practice in nutritional support and its association with mortality in septic patients–results from a national, prospective, multicenter study
SepNet - German Competence Network Sepsis

Abstract (Expand)

OBJECTIVE To identify current clinical practice regarding nutrition and its association with morbidity and mortality in patients with severe sepsis or septic shock in Germany. DESIGN Nationwide …ide prospective, observational, cross-sectional, 1-day point-prevalence study. SETTING The study included 454 intensive care units from a representative sample of 310 hospitals stratified by size. PATIENTS Participants were 415 patients with severe sepsis or septic shock (according to criteria of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference). INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Data were collected by on-site audits of trained external study physicians during randomly scheduled visits during 1 yr. Valid data on nutrition were available for 399 of 415 patients. The data showed that 20.1% of patients received exclusively enteral nutrition, 35.1% exclusively parenteral nutrition, and 34.6% mixed nutrition (parenteral and enteral); 10.3% were not fed at all. Patients with gastrointestinal/intra-abdominal infection, pancreatitis or neoplasm of the gastrointestinal tract, mechanical ventilation, or septic shock were less likely to receive exclusively enteral nutrition. Median Acute Physiology and Chronic Health Evaluation II and Sepsis-related Organ Failure Assessment scores were significantly different among the nutrition groups. Overall hospital mortality was 55.2%. Hospital mortality was significantly higher in patients receiving exclusively parenteral (62.3%) or mixed nutrition (57.1%) than in patients with exclusively enteral nutrition (38.9%) (p = .005). After adjustment for patient morbidity (Acute Physiology and Chronic Health Evaluation II score, presence of septic shock) and treatment factors (mechanical ventilation), multivariate analysis revealed that the presence of parenteral nutrition was significantly predictive of mortality (odds ratio, 2.09; 95% confidence interval, 1.29-3.37). CONCLUSIONS Patients with severe sepsis or septic shock in German intensive care units received preferentially parenteral or mixed nutrition. The use of parenteral nutrition was associated with an increased risk of death.

Authors: Gunnar Elke, Dirk Schädler, Christoph Engel, Holger Bogatsch, Inez Frerichs, Maximilian Ragaller, Jens Scholz, Frank M. Brunkhorst, Markus Löffler, Konrad Reinhart, Norbert Weiler

Date Published: 2008

Publication Type: Journal article

Human Diseases: disease by infectious agent

Practice and perception–a nationwide survey of therapy habits in sepsis
SepNet - German Competence Network Sepsis

Abstract (Expand)

OBJECTIVE To simultaneously determine perceived vs. practiced adherence to recommended interventions for the treatment of severe sepsis or septic shock. DESIGN One-day cross-sectional survey. SETTING …TING Representative sample of German intensive care units stratified by hospital size. PATIENTS Adult patients with severe sepsis or septic shock. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Practice recommendations were selected by German Sepsis Competence Network (SepNet) investigators. External intensivists visited intensive care units randomly chosen and asked the responsible intensive care unit director how often these recommendations were used. Responses \textquotedblalways\textquotedbl and \textquotedblfrequently\textquotedbl were combined to depict perceived adherence. Thereafter patient files were audited. Three hundred sixty-six patients on 214 intensive care units fulfilled the criteria and received full support. One hundred fifty-two patients had acute lung injury or acute respiratory distress syndrome. Low-tidal volume ventilation \textless or = 6 mL/kg/predicted body weight was documented in 2.6% of these patients. A total of 17.1% patients had tidal volume between 6 and 8 mL/kg predicted body weight and 80.3% \textgreater 8 mL/kg predicted body weight. Mean tidal volume was 10.0 +/- 2.4 mL/kg predicted body weight. Perceived adherence to low-tidal volume ventilation was 79.9%. Euglycemia (4.4-6.1 mmol/L) was documented in 6.2% of 355 patients. A total of 33.8% of patients had blood glucose levels \textless or = 8.3 mmol/L and 66.2% were hyperglycemic (blood glucose \textgreater 8.3 mmol/L). Among 207 patients receiving insulin therapy, 1.9% were euglycemic, 20.8% had blood glucose levels \textless or = 8.3 mmol/L, and 1.0% were hypoglycemic. Overall, mean maximal glucose level was 10.0 +/- 3.6 mmol/L. Perceived adherence to strict glycemic control was 65.9%. Although perceived adherence to recommendations was higher in academic and larger hospitals, actual practice was not significantly influenced by hospital size or university affiliation. CONCLUSIONS This representative survey shows that current therapy of severe sepsis in German intensive care units complies poorly with practice recommendations. Intensive care unit directors perceive adherence to be higher than it actually is. Implementation strategies involving all intensive care unit staff are needed to overcome this gap between current evidence-based knowledge, practice, and perception.

Authors: Frank M. Brunkhorst, Christoph Engel, Max Ragaller, Tobias Welte, Rolf Rossaint, Herwig Gerlach, Konstantin Mayer, Stefan John, Frank Stuber, Norbert Weiler, Michael Oppert, Onnen Moerer, Holger Bogatsch, Konrad Reinhart, Markus Loeffler, Christiane Hartog

Date Published: 2008

Publication Type: Journal article

Human Diseases: disease by infectious agent

Informationssysteme in der Medizin
Management of health information systems

Abstract (Expand)

Zusammenfassung&nbsp;&nbsp;Die Medizin ist geprägt sowohl durch ihren besonderen unmittelbaren und existenziellen Bezug zu Menschen als auch durch ihre zunehmende Ã\Pkonomische Bedeutung. Ein … Medizinisches Informationssystem ist das umfassende System aller Informationsverarbeitung einer medizinischen Einrichtung oder Region. Während die Architekturprinzipien des rechnerbasierten Teils solcher Informationssysteme wenige Besonderheiten aufweist, bÃ\textonequarterndelt das Management dieser Informationssysteme viele Herausforderungen und Probleme, die wegen der besonderen Bedeutung der Medizin besondere Priorität bei der LÃ\Psung haben mÃ\textonequarterssen.

Author: Alfred Winter

Date Published: 2008

Publication Type: Journal article

Ethische Leitlinien von GMDS, AL-KRZ, BVMI, KH-IT und DVMD
Management of health information systems

Abstract

Not specified

Authors: Alfred Winter, W. Ahrens, B. Bergh, M. Bohrer-Steck, J. Chang-Claude, H. Christ, Thomas M. Deserno, C. Dujat, J. Haerting, C. O. Köhler, U. Kutscha, O. Mosbach-Schulz, J. Müller, A. Mulder-Rathgeber, W. Niederlag, M. Niehsen-Zehrer, K. Pommerening, A. Scharsky, C. Stark, R. Vollmar

Date Published: 2008

Publication Type: Journal article

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