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  • 1
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  Deutscher Kongress für Orthopädie und Unfallchirurgie; 72. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie, 94. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie, 49. Tagung des Berufsverbandes der Fachärzte für Orthopädie; 20081022-20081025; Berlin; DOCWI59-1110 /20081016/
    Publication Date: 2008-10-17
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 2
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    Springer Verlag
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  • 3
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  Deutscher Kongress für Orthopädie und Unfallchirurgie; 73. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie, 95. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie, 50. Tagung des Berufsverbandes der Fachärzte für Orthopädie; 20091021-20091024; Berlin; DOCEF17-236 /20091015/
    Publication Date: 2009-10-16
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 4
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  Deutscher Kongress für Orthopädie und Unfallchirurgie; 72. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie, 94. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie, 49. Tagung des Berufsverbandes der Fachärzte für Orthopädie; 20081022-20081025; Berlin; DOCWI59-862 /20081016/
    Publication Date: 2008-10-17
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 5
    Keywords: RECEPTOR ; CANCER ; EXPRESSION ; GROWTH ; IN-VITRO ; tumor ; carcinoma ; Germany ; human ; INFORMATION ; ENZYMES ; PROTEIN ; DRUG ; METABOLISM ; DIFFERENTIATION ; TISSUE ; TUMORS ; PATIENT ; prognosis ; ASSOCIATION ; ALPHA ; BREAST ; breast cancer ; BREAST-CANCER ; hormone ; PROGRESSION ; immunohistochemistry ; TUMOR PROGRESSION ; METASTASIS ; cancer risk ; CARCINOMAS ; HUMAN LIVER ; CARCINOGENS ; GST ; ESTROGEN-RECEPTOR ; glutathione-S-transferase ; GLUTATHIONE S-TRANSFERASE ; cytochrome P450 ; FEATURES ; ASSOCIATIONS ; TUMOR-GROWTH ; CARCINOGEN ; ESTROGEN ; ENZYME ; CANCER DEVELOPMENT ; estrogen receptor ; breast carcinoma ; HORMONES ; lymph node ; LYMPH-NODE ; GLUTATHIONE S-TRANSFERASES ; CYP ; CYP1B1 ; CYP3A5 ; CYTOCHROME-P450 ENZYMES ; IMMUNOHISTOCHEMICAL-DEMONSTRATION ; NONTUMOR TISSUES ; progesterone receptor
    Abstract: The potential to metabolize endogenous and exogenous substances may influence breast cancer development and tumor growth. Therefore, the authors investigated the protein expression of Glutathione S-transferase (GST) isoforms and cytochrome P450 (CYP) known to be involved in the metabolism of steroid hormones and endogenous as well as exogenous carcinogens in breast cancer tissue to obtain new information on their possible role in tumor progression. Expression of GST pi, mu, alpha and CYP1A1/2, 1A2, 3A4/5, 1B1, 2E1 was assessed by immunnhistochemistry for primary breast carcinomas of 393 patients from the German GENICA breast cancer collection. The percentages of positive tumors were 50.1 and 44.5% for GST mu and CYP2E1, and ranged from 13 to 24.7% for CYP1A2, GST pi, CYP1A1/2, CYP3A4/5, CYP1B1. GST alpha was expressed in 1.8% of tumors. The authors observed the following associations between strong protein expression and histopathological characteristics: GST expression was associated with a better tumor differentiation (GST mu, p = 0.018) and with reduced lymph node metastasis (GST pi, p = 0.02). In addition, GST mu expression was associated with a positive estrogen receptor and progesterone receptor status (p 〈 0.001). CYP3A4/5 expression was associated with a positive nodal status (p = 0.018). Expression of CYP1B1 was associated with poor tumor differentiation (p = 0.049). Our results demonstrate that the majority of breast carcinomas expressed xenobiotic and drug metabolizing enzymes. They particularly suggest that GST mu and pi expression may indicate a better prognosis and that strong CYP3A4/5 and CYP1B1 expression may be key features of nonfavourable prognosis. (c) 2006 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 16721811
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  • 6
    Keywords: EXPRESSION ; SURVIVAL ; tumor ; Germany ; MODEL ; CLASSIFICATION ; DIAGNOSIS ; SYSTEM ; SYSTEMS ; COHORT ; DISEASE ; RISK ; DISTINCT ; GENE ; GENE-EXPRESSION ; microarray ; ACCURACY ; validation ; PATIENT ; BREAST-CANCER ; STAGE ; TRIAL ; TRIALS ; gene expression ; microarrays ; DELETIONS ; HIGH-RISK ; PROBES ; UNITED-STATES ; PREDICTION ; pathology ; CHILDREN ; DIFFERENTIAL EXPRESSION ; neuroblastoma ; INTEGRATION ; REGRESSION ; SIGNATURE ; PREDICTOR ; SPECIMENS ; SUBGROUPS ; PREDICTS ; SET ; CLINICAL COURSE ; 11Q
    Abstract: Purpose To develop a gene expression - based classifier for neuroblastoma patients that reliably predicts courses of the disease. Patients and Methods Two hundred fifty-one neuroblastoma specimens were analyzed using a customized oligonucleotide microarray comprising 10,163 probes for transcripts with differential expression in clinical subgroups of the disease. Subsequently, the prediction analysis for microarrays (PAM) was applied to a first set of patients with maximally divergent clinical courses ( n = 77). The classification accuracy was estimated by a complete 10-times-repeated 10-fold cross validation, and a 144-gene predictor was constructed from this set. This classifier's predictive power was evaluated in an independent second set ( n = 174) by comparing results of the gene expression based classification with those of risk stratification systems of current trials from Germany, Japan, and the United States. Results The first set of patients was accurately predicted by PAM (cross-validated accuracy, 99%). Within the second set, the PAM classifier significantly separated cohorts with distinct courses (3-year event-free survival [EFS] 0.86 +/- 0.03 [ favorable; n = 115] v 0.52 +/- 0.07 [ unfavorable; n = 59] and 3-year overall survival 0.99 +/- 0.01 v 0.84 +/- 0.05; both P 〈.0001) and separated risk groups of current neuroblastoma trials into subgroups with divergent outcome (NB2004: low-risk 3-year EFS 0.86 +/- 0.04 v 0.25 +/- 0.15, P 〈.0001; intermediate-risk 1.00 v 0.57 +/- 0.19, P =.018; high-risk 0.81 +/- 0.10 v 0.56 +/- 0.08, P =.06). In a multivariate Cox regression model, the PAM predictor classified patients of the second set more accurately than risk stratification of current trials from Germany, Japan, and the United States ( P 〈.001; hazard ratio, 4.756 [95% CI, 2.544 to 8.893]). Conclusion Integration of gene expression - based class prediction of neuroblastoma patients may improve risk estimation of current neuroblastoma trials
    Type of Publication: Journal article published
    PubMed ID: 17075126
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  • 7
    Keywords: ENVIRONMENT ; CELLS ; EXPRESSION ; GROWTH ; SURVIVAL ; CELL ; Germany ; IN-VIVO ; SYSTEM ; GENE ; GENES ; PROTEIN ; PROTEINS ; METABOLISM ; INFECTION ; SEQUENCE ; CARBON ; ESCHERICHIA-COLI ; resistance ; FUSION ; PCR ; HOMOLOG ; OXIDATIVE STRESS ; TRANSPORTER ; REPORTER GENE ; analysis ; PHASE ; STAPHYLOCOCCUS-AUREUS ; microbiology ; ENGLAND ; EXCLUSION ; BACILLUS-SUBTILIS ; quantitative ; GRAM-POSITIVE BACTERIA ; bacterial ; BILE-SALT HYDROLASE ; COMPARATIVE GENOMICS ; GENERAL STRESS-RESPONSE ; GLUTAMATE-DECARBOXYLASE ; VIRULENCE FACTOR
    Abstract: Background: The opportunistic food-borne gram-positive pathogen Listeria monocytogenes can exist as a free-living microorganism in the environment and grow in the cytoplasm of vertebrate and invertebrate cells following infection. The general stress response, controlled by the alternative sigma factor, sigma(B), has an important role for bacterial survival both in the environment and during infection. We used quantitative real-time PCR analysis and immuno-blot analysis to examine sB expression during growth of L. monocytogenes EGD-e. Whole genome-based transcriptional profiling was used to identify sigma(B)-dependent genes at different growth phases. Results: We detected 105 sigma(B)-positively regulated genes and 111 genes which appeared to be under negative control of sB and validated 36 sigma(B)-positively regulated genes in vivo using a reporter gene fusion system. Conclusion: Genes comprising the sigma(B) regulon encode solute transporters, novel cell-wall proteins, universal stress proteins, transcriptional regulators and include those involved in osmoregulation, carbon metabolism, ribosome-and envelope-function, as well as virulence and niche-specific survival genes such as those involved in bile resistance and exclusion. Ten of the sigma(B)-positively regulated genes of L. monocytogenes are absent in L. innocua. A total of 75 sigma(B)-positively regulated listerial genes had homologs in B. subtilis, but only 33 have been previously described as being sigma(B)-regulated in B. subtilis even though both species share a highly conserved sigma(B)-dependent consensus sequence. A low overlap of genes may reflects adaptation of these bacteria to their respective environmental conditions
    Type of Publication: Journal article published
    PubMed ID: 18226246
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  • 8
    Keywords: IN-VIVO ; GENOME ; DIFFERENTIATION ; HEMATOPOIETIC STEM-CELLS ; ACUTE MYELOID-LEUKEMIA ; Hox genes ; SELF-RENEWAL ; QUIESCENCE ; LINEAGE COMMITMENT ; LONG NONCODING RNAS
    Abstract: In this study, we present integrated quantitative proteome, transcriptome, and methylome analyses of hematopoietic stem cells (HSCs) and four multipotent progenitor (MPP) populations. From the characterization of more than 6,000 proteins, 27,000 transcripts, and 15,000 differentially methylated regions (DMRs), we identified coordinated changes associated with early differentiation steps. DMRs show continuous gain or loss of methylation during differentiation, and the overall change in DNA methylation correlates inversely with gene expression at key loci. Our data reveal the differential expression landscape of 493 transcription factors and 682 lncRNAs and highlight specific expression clusters operating in HSCs. We also found an unexpectedly dynamic pattern of transcript isoform regulation, suggesting a critical regulatory role during HSC differentiation, and a cell cycle/DNA repair signature associated with multipotency in MPP2 cells. This study provides a comprehensive genome-wide resource for the functional exploration of molecular, cellular, and epigenetic regulation at the top of the hematopoietic hierarchy.
    Type of Publication: Journal article published
    PubMed ID: 25158935
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  • 9
  • 10
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  GMS Health Technology Assessment; VOL: 3; DOC04 /20070327/
    Publication Date: 2007-08-24
    Description: Health political background Methadone substitution treatment in Germany is introduced in 1988 in the framework of a scientific pilot study in North Rhein Westphalia. Recent statistics show that by now a broad offer of substitution treatment exists. From 1 June 2002 to 31 December 2003 113,000 substitution treatments have been recorded as being started of which around 56,000 have been recorded as ongoing treatments by 1 December 2003. Scientific background Substitution treatment (treatment of opioid-dependent persons using substitution substances) is one part of addiction treatment. Its goals are harm reduction and the stabilisation of opioid dependent persons. Integration of opioid-dependent persons in a treatment-setting, reduction of consumption of psychoactive substances, reduction of risk behaviour (primarily related to infectious diseases), decrease of mortality and improvements concerning the social, psychic and physic situation are seen as a success of substitution treatment as maintenance therapy. Research questions The aim of this HTA report is to investigate which indicators can be used to evaluate the effectiveness of substitution treatment. Based on these indicators an evaluation of the medical, social and economical benefit of substitution treatment - also in relation to abstinence oriented treatment - is carried out. Methods A systematic literature search was performed in 31 international databases which yielded 2451 articles with publication date between 1995 and February 2005. Results After a twofold selection process 32 publications were included for assessment and 276 publications were used as background literature. Despite serious restrictions due to selection bias and dropout in most studies focusing on substitution treatment, reduction of consumption of illegal opioids, reduction of risk behaviour, criminal behaviour, mortality and incidence of HIV can be seen as an empirically proven success of substitution treatment. Concerning the improvement of life and health situation the results of the studies are contradictory. The results show that retention rate of substitution treatment is higher than retention rate of abstinence oriented treatment. Regarding economical aspects substitution treatment is efficient in avoiding secondary illnesses (infections) and decreasing criminality. From the perspective of medical ethics substitution treatment as well as medical prescription of heroin is in principle acceptable. Discussion and conclusions Based on these results, it can be recommended that substitution treatment in principle should be made available for all opioid dependent persons. The decision whether substitution treatment or another treatment (e. g. abstinence oriented treatment) is more promising has to take into account the individual situation of the client. In addition a combination of substitution treatment and abstinence oriented treatment might be promising although there is a lack of studies about this approach. In any case the decision concerning a certain form of treatment should leave aside pseudo-moralic concerns and should be made on the base of established medical ethic principles - like the interest of the patient - taking into account the specific situation of the client.
    Description: Gesundheitspolitischer Hintergrund In der Bundesrepublik Deutschland wird 1988 im Rahmen eines begrenzten wissenschaftlichen Erprobungsvorhabens in Nordrhein-Westfalen die Substitutionsbehandlung mit Methadon eingeführt. Aktuelle Zahlen und Informationen bestätigen, dass es inzwischen ein breites Angebot an Substitutionsbehandlung in Deutschland gibt. Von 1. Juni 2002 bis 31. Dezember 2003 sind 113.000 begonnene Substitutionsbehandlungen gemeldet, von denen am 1. Dezember 2003 etwa 56.000 laufende Behandlungen betreffen. Wissenschaftlicher Hintergrund Die Substitutionsbehandlung, in deren Rahmen opioidabhängige Personen mit Substitutionsmitteln therapiert werden, ist ein Teil der Suchttherapie und soll neben der Schadensminimierung vor allem zur Stabilisierung opioidabhängiger Personen beitragen. Bei der Substitutionsbehandlung als Erhaltungstherapie werden das Integrieren von opiatabhängigen Personen in ein Behandlungssetting, die Reduktion des Konsums psychoaktiver Substanzen, die Reduktion des Risikoverhaltens (vor allem hinsichtlich Infektionskrankheiten), die Senkung der Mortalität sowie Verbesserungen in sozialer, psychischer und physischer Hinsicht als Erfolg gesehen. Fragestellung Es soll geklärt werden, anhand welcher Indikatoren die Wirksamkeit der Substitutionstherapie beurteilt werden kann und basierend auf den ermittelten Indikatoren eine Bewertung des medizinischen, sozialen und ökonomischen Nutzens dieser Therapieform - auch im Vergleich zu abstinenzorientierten Ansätzen - vorgenommen werden. Methode Eine systematische Literatursuche im Suchzeitraum 1995 bis Februar 2005 in insgesamt 31 Datenbanken der DIMDI-Superbase ergibt insgesamt 2451 Treffer. Ergebnisse Nach einem zweiteiligen Selektionsprozess verbleiben 32 bewertete Studien und 276 Arbeiten als Hintergrundliteratur. Trotz erheblicher methodischer Einschränkungen der meisten Studien zur Substitutionsbehandlung durch Selektionsbias und Dropout, kann auf Basis des empirischen Befunds eine Reduktion des illegalen Opioidkonsums, eine Verringerung des Risikoverhaltens, der Kriminalität, der Mortalität und der HIV-Inzidenz als nachgewiesen angesehen werden. Hinsichtlich der Verbesserung von Lebenssituation und Gesundheit sind die Ergebnisse widersprüchlich. Die referierten Befunde ergeben, dass Substitution eine höhere Haltequote aufweist als abstinenzorientierte Therapieformen. Substitutionsbehandlung erweist sich im Bereich der Vermeidung von Folgeerkrankungen (Infektionen) und der Senkung von Kriminalität als ökonomisch sinnvolle Maßnahme. Erfolgt eine Bewertung auf Basis von medizinethischen Kriterien, so ist sowohl die Substitutionsbehandlung als auch die ärztliche Heroinverschreibung prinzipiell akzeptable Behandlungsangebote. Diskussion und Schlussfolgerung Aus diesen Gründen ist die prinzipielle Verfügbarkeit von Substitutionsbehandlung für alle Opioidabhängigen zu befürworten. Bei der Beurteilung, ob eine Substitutionsbehandlung oder eine andere Form der Therapie (z. B. abstinenzorientierte Behandlung) mehr Erfolg verspricht, muss auf die individuelle Problemlage und Situation der Klientin bzw. des Klienten Bezug genommen werden. Erfolgversprechend kann auch eine Kombination aus Substitutionsbehandlung und abstinenzorientierter Therapie sein. Hier besteht allerdings ein großes Forschungsdesiderat, da nur vereinzelt Studien existieren, die das Ineinandergreifen von Substitutionstherapie und abstinenzorientierten Therapieansätzen behandeln. In jedem Fall sollten bei der Entscheidung für eine bestimmte Therapieform pseudo-moralische Bedenken ausgeklammert werden und es sollte im Einklang mit der spezifischen Situation auf Basis der etablierten medizinethischen Prinzipien - wie das Wohl der Patientin bzw. des Patienten - vorgegangen werden.
    Keywords: SUBSTANCE-RELATED DISORDERS ; DRUG THERAPY ; ECONOMICS ; PUBLIC HEALTH ; QUALITY OF LIFE ; ETHICS ; SUBSTANZBEZOGENEN STÖRUNGEN ; ARZNEIMITTELTHERAPIE ; ÖKONOMIE ; ÖFFENTLICHES GESUNDHEITSWESEN ; LEBENSQUALITÄT ; ETHIK ; Opiatabhängigkeit ; Substitutionstherapie ; Methadon ; Buprenorphin ; Heroin ; abstinenzorientierte Therapie ; Langzeittherapie ; Wirksamkeit ; Kosten-Nutzen-Analyse ; Mortalität ; Morbidität ; Ethik ; sozioökonomische Aspekte ; ddc: 610
    Language: German
    Type: article
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