Search PubMed⌕ Search

Biomedical subjects

Uwe Koch

Publications and source records attributed to Uwe Koch.

At least 37 records · Page 2Linked to original sources
PubMed2005

[Rehabilitative elements for the treatment of patients with mental disorders: are they considered in the development of guidelines?].

OBJECTIVE: In the context of the current discussion of integrating rehabilitative elements into the (acute) treatment of patients with mental disorders, it is investigated what rehabilitative elements actually are and whether these elements are considered in existing guidelines. METHODS/RESULTS: An expert-based consensus, especially results of expert ratings using a 46-item questionnaire (Delphi Technique; n = 16), shows that it is possible to specify rehabilitative elements, although there are still aspects which need further clarification. Analyses of current guidelines (using published guidelines for panic disorders) demonstrate that rehabilitative elements which are rated as important by the experts are only marginally mentioned in guidelines up to now. CONCLUSIONS: A considerable need for research exists for a further specification of rehabilitative elements and for the development of evidence based recommendations in the form of guidelines.

Consensus↗
PubMed2005

Detection of electrophysiological indicators of neurotoxicity in human and rat brain slices by a three-dimensional microelectrode array.

Electrophysiological techniques for the assessment of in vitro neurotoxicology have several advantages over other currently-used methods (for example, morphological techniques), including the ability to detect damage at a very early stage. Novel recording techniques based on microelectrode arrays are available, and could improve recording power. In this study, we investigated how a three-dimensional microelectrode array detects the electrophysiological endpoints of neurotoxicity. We conclude that electrophysiology sensitively reveals neurotoxic actions, and that three-dimensional microelectrode arrays could be proposed for use in neurotoxicology as recording tools that allow easy and sensitive multisite recording, from both rodent and human brain tissue.

Animals↗
PubMed2005

[Demands on the evaluation of complex healthcare programs--disease management in Germany].

Disease management programs (DMP) are a new method of healthcare in Germany. Their implementation is legally secured and binding. Besides the requirements of a comprehensive documentation and the obligation to provide guideline-oriented healthcare, the statutory health insurances are also obliged to carry out a DMP evaluation. For this evaluation, a scientific advisory council of the Federal Insurance Office has submitted specific relevant criteria. The present contribution considers these criteria and relates them to the evaluation standards of the Evaluation Research Society. Additionally, some specific conditions for the undertaking of DMP and their evaluation in Germany are taken into consideration. The article ends with a suggestion for a comprehensive and methodologically accurate discussion.

Delivery of Health Care↗
PubMed2004

The design and enzyme-bound crystal structure of indoline based peptidomimetic inhibitors of hepatitis C virus NS3 protease.

The design of a series of peptidomimetic inhibitors of the hepatitis C virus NS3 protease is described. These inhibitors feature an indoline-2-carboxamide as a novel heterocyclic replacement for the P3 amino acid residue and N-terminal capping group of tripeptide based inhibitors. The crystal structure of the ternary NS3/NS4A/inhibitor complex for the most active molecule in this series highlights its suitability as an N-terminal capping group of a dipeptide inhibitor of the NS3 protease.

Antiviral Agents↗
PubMed2004

Capped dipeptide phenethylamide inhibitors of the HCV NS3 protease.

The N-terminal aminoacid of phenethylamide tripeptide inhibitors of the hepatitis C virus NS3 protease can be replaced with an alpha-hydroxy acid to obtain more 'drug like' inhibitors with low micromolar activity. The preferred S-configuration of the capping residue can be explained by molecular modeling studies.

Amides↗
PubMed2004

Discovery of alpha,gamma-diketo acids as potent selective and reversible inhibitors of hepatitis C virus NS5b RNA-dependent RNA polymerase.

alpha,gamma-Diketo acids (DKA) were discovered from screening as selective and reversible inhibitors of hepatitis C virus NS5b RNA-dependent RNA polymerase. The diketo acid moiety proved essential for activity, while substitution on the gamma position was necessary for selectivity and potency. Optimization led to the identification of a DKA inhibitor of NS5b polymerase with IC(50) = 45 nM, one of the most potent HCV NS5b polymerase inhibitors reported.

Keto Acids↗
PubMed2004

Psychometric properties of the EORTC Quality of Life Questionnaire in inpatient cancer rehabilitation in Germany.

OBJECTIVE: Recent years have shown an increase in the use of questionnaires measuring health-related quality of life to verify the quality of treatment in the field of oncology. An often used cancer-specific questionnaire is the "Quality of Life Core Questionnaire of the European Organization for the Research and Treatment of Cancer" (EORTC QLQ-C30). The purpose of this study is to analyze the psychometric properties of the EORTC QLQ-C30 (version 1) in order to determine the feasibility and appropriateness for its use in inpatient cancer rehabilitation in Germany with heterogeneous diagnoses. METHODS: The questionnaire was administrated to a sample of 972 cancer patients at the beginning of treatment and to 892 patients after treatment. Besides descriptive analysis, the statistical analyses include confirmatory analysis and the multitrait/multimethod approach to test the questionnaire's postulated scale structure (factorial validity) and its reliability (internal consistencies). The analysis also includes a comparison of responsiveness indices (effect size, reliable change index) to test the sensitivity of the instrument. RESULTS: The EORTC QLQ-C30 showed satisfactory levels of reliability and sensitivity, but the postulated scale structure could not be confirmed. The results illustrate that the varimax-rotated solution of a principal component analysis does not confirm the scale structure postulated by the authors. Correspondingly, the selected fit indices within the scope of the confirmatory factor analysis do not show satisfactory results either. SIGNIFICANCE OF RESULTS: We therefore consider version 1 of the EORTC QLQ-C30 to be only limitedly useful for the routine assessment of changes in the quality of life of cancer patients in inpatient rehabilitation in Germany, especially because of the instrument's length and possible redundancies. For this reason, a scoring procedure limited to a subset of items is suggested, revealing satisfactory to good psychometric indices. However, further psychometric tests are necessary, especially with regard to validity and sensitivity.

Female↗
PubMed2004

[Predictors of resource use in inpatient psychotherapy: development of a German case group concept for patients with mental disorders].

OBJECTIVE: Recent research on predictors of resource use in inpatient psychotherapy indicates that various patient characteristics as well as therapeutic factors may influence resource use. The aim of our study was to examine the relationship between patient attributes and psychotherapeutic costs in German inpatient psychotherapy. The amount of variance explained in resource use was calculated. METHOD: The existing sample used in this study consists of sociodemographic and clinical variables of 2375 patients treated in various inpatient psychosomatic clinics. Resource use was measured on the basis of clinical staff activities (Klassifikation Therapeutischer Leistungen, KTL, BfA 2000). Regression Tree Analysis was performed to classify patient attributes based on resource use. RESULTS: The model assigns patients to 20 classes, accounting for 17.5 % of variance. Those patients with single status and personality or eating disorder consume more resources than those patients with non-single status, low motivation for psychotherapy, comorbidity of physical illness and lower levels on symptom severity. CONCLUSIONS: Implications of the results for the development of a patient classification system in inpatient psychotherapy will be discussed.

Aged↗
PubMed2004

Characterization of the inhibition of hepatitis C virus RNA replication by nonnucleosides.

The RNA-dependent RNA polymerase of hepatitis C virus (HCV) is necessary for the replication of viral RNA and thus represents an attractive target for drug development. Several structural classes of nonnucleoside inhibitors (NNIs) of HCV RNA polymerase have been described, including a promising series of benzothiadiazine compounds that efficiently block replication of HCV subgenomic replicons in tissue culture. In this work we report the selection of replicons resistant to inhibition by the benzothiadiazine class of NNIs. Four different single mutations were identified in separate clones, and all four map to the RNA polymerase gene, validating the polymerase as the antiviral target of inhibition. The mutations (M414T, C451R, G558R, and H95R) render the HCV replicons resistant to inhibition by benzothiadiazines, though the mutant replicons remain sensitive to inhibition by other nucleoside and NNIs of the HCV RNA polymerase. Additionally, cross-resistance studies and synergistic inhibition of the enzyme by combinations of a benzimidazole and a benzothiadiazine indicate the existence of nonoverlapping binding sites for these two structural classes of inhibitors.

Antiviral Agents↗
PubMed2004

[Clinic comparisons as an instrument for quality assurance in the treatment of patients with mental disorders: the significance of risk adjustment].

It is becoming increasingly more relevant for health care providers to also participate in external quality assurance measures. A few systematic approaches that also integrate outcome quality and include a comparison of different clinics have only recently been developed for the area of the treatment of patients with mental disorders. In this context, a key issue is the appropriate consideration of confounders, i.e., of unevenly distributed patient characteristics that are causally related to the treatment results. Using a sample of consecutive patients from four psychotherapeutic clinics, we exemplarily examined the significance of the confounders for the comparison of the clinics with regard to short-term outcome. The results show that an adjustment is principally advisable and is generally associated with a reduction of the differences in treatment results. The discussion asserts that the use of regression weights, which were ascertained using an independent, representative sample, allows for a more valid risk adjustment. Finally, reference will be made to the relevance of giving consideration to varying resource usage in the assessment of the risk-adjusted clinic comparisons.

Humans↗
PubMed2003

Novel, potent phenethylamide inhibitors of the hepatitis C virus (HCV) NS3 protease: probing the role of P2 aryloxyprolines with hybrid structures.

Synthesis of hybrid HCV NS3 protease/NS4A inhibitors having the 4,4-difluoroaminobutyric acid (difluoroAbu) phenethylamides as P1-P1' and quinolyloxyprolines as P2 fragments led to 7 (IC(50) 54 nM). Molecular modelling suggests that this potent tripeptide inhibitor utilizes interactions in the S1', S1, S2, S3 and S4 sites of the protease.

Aminobutyrates↗
PubMed2003

Phenethyl amides as novel noncovalent inhibitors of hepatitis C virus NS3/4A protease: discovery, initial SAR, and molecular modeling.

The discovery of novel, reversible and competitive tripeptide inhibitors of the Hepatitis C virus NS3/4A serine protease is described. These inhibitors are characterized by the presence of a C-terminal phenethyl amide group, which extends into the prime side of the enzyme. Initial SAR together with molecular modeling and data from site-directed mutagenesis suggest an interaction of the phenethyl amide group with Lys-136.

Amides↗
PubMed2003

Knowledge and attitudes of gynecologists regarding genetic counseling for hereditary breast and ovarian cancer.

In a survey we investigated whether gynecologists are sufficiently knowledgeable to perform genetic counseling. It provides information for the development and evaluation of a counseling manual for professionals in primary health care. The members of the sample, consisting of 529 gynecologists in northern Germany, were mailed a questionnaire concerning their knowledge of and attitudes towards genetic counseling and testing for hereditary breast and ovarian cancer (HBOC). The response rate was 32.5% (n = 172). The majority of the respondents (82%) have received requests from patients for genetic testing. Most would offer basic genetic counseling to their patients, 66% feel knowledgeable enough to do so. Physicians set high value on communicating clinical management options, but also consider psychosocial aspects to be important. The results suggest that HBOC genetics play a noticeable role in the practice of gynecology in Germany. There is consensus about the need for further educational training to deal with cancer genetics in physicians' daily practice.

Adult↗