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- Juth, Niklas, 1973, et al.
(author)
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The Ethics of Screening in Health Care and Medicine: Serving Society or Serving the Patient?
- 2012
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Book (other academic/artistic)abstract
- Medical or health-oriented screening programs are amongst the most debated aspects of health care and public health practices in health care and public health ethics, as well as health policy discussions. In spite of this, most treatments of screening in the research literature restrict themselves to isolated scientific aspects, sometimes complemented by economic analyses or loose speculations regarding policy aspects. At the same time, recent advances in medical genetics and technology, as well as a rapidly growing societal focus on public health concerns, inspires an increase in suggested or recently started screening programs. This book involves an in-depth analysis of the ethical, political and philosophical issues related to health-oriented screening programs. It explores the considerations that arise when heath care interacts with other societal institutions on a large scale, as is the case with screening: What values may be promoted or compromised by screening programs? What conflicts of values do typically arise – both internally and in relation to the goals of health care, on the one hand, and the goals of public health and the general society, on the other? What aspects of screening are relevant for determining whether it should be undertaken or not and how it should be organised in order to remain defensible? What implications does the ethics of screening have for health care ethics as a whole? These questions are addressed by applying philosophical methods of conceptual analysis, as well as models and theories from moral and political philosophy, medical ethics, and public health ethics, to a large number of ongoing and proposed screening programs which makes this book the first comprehensive work on the ethics of screening. Analyses and suggestions are made that are of potential interest to health care staff, medical researchers, policy makers and the general public.
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| 2. |
- Bin Kaderi, Mohamed Arifin, 1978-
(author)
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Assessment of Novel Molecular Prognostic Markers in Chronic Lymphocytic Leukemia
- 2010
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Doctoral thesis (other academic/artistic)abstract
- The clinical course of chronic lymphocytic leukemia (CLL) is highly heterogeneous, which has prompted the search for biomarkers that can predict prognosis in this disease. The IGHV gene mutation status and certain genomic aberrations have been identified as reliable prognostic markers of clinical outcome for this disorder. However, the search for more feasible prognostic markers in CLL is still being pursued. Recently, certain single nucleotide polymorphisms (SNPs) in the GNAS1, BCL2 and MDM2 genes and the RNA expression levels of the LPL, ZAP70, TCL1, CLLU1 and MCL1 genes were suggested as novel prognostic markers in CLL. In papers I-III, we performed genotyping analyses of the GNAS1 T393C, BCL2 -938C>A and MDM2 SNP309 polymorphisms in 268-418 CLL patients and related the genotypes with clinical data. Association studies between the polymorphisms and established prognostic markers (i.e. IGHV mutation status, genomic aberrations, CD38 expression) were also performed. Our studies did not find any significant relationship between these SNPs with either clinical outcome or other known prognostic markers in CLL. In paper IV, we measured the RNA expression levels of LPL, ZAP70, TCL1, CLLU1 and MCL1 in 252 CLL cases and correlated these levels with clinical outcome. Here, we verified that high expression of all these RNA-based markers, except MCL1, were associated with an unfavourable prognosis. We also confirmed a close relationship between IGHV mutation status and the RNA-based markers, especially for LPL and CLLU1 expression. Among the RNA-based markers, multivariate analysis revealed LPL expression as the strongest independent prognostic marker for overall survival and time to treatment. Furthermore, the RNA-based markers could add further prognostic information to established markers in subgroups of patients, with LPL expression status giving the most significant results. In summary, data from papers I-III could not verify the GNAS1 T393C, BCL2 -938C>A and MDM2 SNP309 polymorphisms as prognostic markers in CLL. Future SNP markers must hence be confirmed in large, independent cohorts before being proposed as prognostic marker in CLL. In paper IV, we conclude that LPL expression appears to be the strongest among the RNA-based markers for CLL prognostication. Further efforts to standardize LPL quantification are required before it can be applied in the clinical laboratory to predict clinical outcome in this disease.
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| 3. |
- Munthe, Christian, 1962
(author)
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Etiska aspekter på regenerativ medicin : Ethical aspects on regenerative medicine
- 2003
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In: SNIB-konferensen 2003, Chalmers tekniska högskola, Göteborg, 16-18 maj 2003.
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Conference paper (other academic/artistic)abstract
- Inom den regenerativa medicinen strävar man efter att ersätta skadat eller sjukligt biologiskt mänskligt material (celler, organ, kroppsdelar) med nya biologiska komponenter. Området aktualiserar en rad etiska frågeställningar vad gäller (1) produktionen av ersättningsmaterialet (t.ex. embryonala stamceller eller införskaffande av transplantationsvävnad från donatorer), (2) risker i samband med försök på människa (genmodifierat material, material från djur), samt (3) gränserna för hur långt man bör gå i denna slags försök att förlänga människans livsspann. Föredraget ger en kort översikt över dessa frågeställningar, ståndpunkter och argument i debatten kring dem.
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| 4. |
- Norberg, Maria, 1976-
(author)
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In Vitro Drug Sensitivity and Apoptosis in Chronic Lymphocytic Leukemia
- 2010
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Doctoral thesis (other academic/artistic)abstract
- Chronic lymphocytic leukemia (CLL) is a heterogeneous malignancy displaying varying clinical outcome, where molecular markers today can divide patients into prognostic subgroups. Despite the introduction of new agents for treatment, remissions are usually not sustained in CLL and resistance towards treatment can partly be explained by aberrant apoptosis. The aim of this thesis was to find new drugs for CLL patients resistant to conventional therapy and to analyze genes involved in apoptosis within different prognostic subgroups. In paper I-II, the in vitro activity of substances was investigated using the fluorometric microculture cytotoxicity assay (FMCA). When evaluating rapamycin (paper I), an inhibitor of mTOR, in 97 tumor samples from different entities, CLL was found to be one of the most sensitive tumor types. Combination experiments on patient CLL cells indicated that rapamycin acted synergistically with the CLL drugs vincristine and chlorambucil. An investigation of 20 anti-cancer agents in cells from 40 CLL patients (paper II) revealed that prednisolone and rolipram displayed high activity in poor-prognostic patients, in particular IGHV unmutated CLL. Furthermore, when used in combination these agents were found to produce a synergistic effect. In paper III, the anti-apoptotic BCL2 family member BFL1 was evaluated in 37 CLL cases. Levels of BFL1 were higher in fludarabine-resistant patients compared to fludarabine-sensitive patients. In addition, the high expression of BFL1 inversely correlated to fludarabine-induced apoptosis in CLL cells. A single nucleotide polymorphism in the anti-apoptotic BCL2 gene (-938C>A) has been suggested as a novel poor-prognostic marker in CLL. In paper IV, we investigated this BCL2 polymorphism in 268 CLL patients and correlated genotypes to clinical data. However, no association could be confirmed between this polymorphism and clinical outcome or established prognostic markers. In conclusion, this thesis has shown that rapamycin is a potential drug for treatment in CLL. Furthermore, prednisolone and rolipram were identified as interesting candidates for treatment of poor-prognostic patients. Finally, the anti-apoptotic protein BFL1 may contribute to chemoresistance and hence represents a potential therapeutic target in CLL, whereas from our data, the BCL2 -938C>A polymorphism does not appear to have any prognostic significance.
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| 6. |
- Munthe, Christian, 1962
(author)
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Pure Selection. The Ethics of Preimplantation Genetic Diagnosis and Choosing Children without Abortion
- 1999
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Book (other academic/artistic)abstract
- Preimplantation ge¬netic diagnosis (PGD) is taken to mark the starting-point of a new phase in human reproduction, where the possibility of choosing children on genetic grounds without having to resort to ethi¬cally controversial procedures (such as abortion) will grad¬ually increase. Ethical and political issues actu¬alised by this develop¬ment are addressed. The discussion touches upon issues regarding the moral status of em¬bryos and gametes, the moral import of respecting individual auton¬omy and its implications for the requirement of informed consent in health-care, the connec¬tion between sickness, dis¬ability and the value of life, the moral status of possible future people, and the connection between choosing children and eugenic policies of the past. Practical policy issues are adressed on the basis of this, as well as an empirical case-study of the intro¬duction of PGD in Sweden. The book ends up in a set of recommendations regarding the management of re¬search on, introduction and routine use of procedures for pure se¬lection, both within health care and from the point of view of society as a whole. It is argued that research on such procedures should be allowed and supported by society. However, tight restrictions regarding the clinical introduction of new procedures in this area is highly desirable. A rough model for implementing such re¬strictions is also pre¬sented. It is further asserted that, although reasons of economy and safety should limit the access to pure se¬lection, society should not apply any explicit restrictions based on ideasregarding how different traits affect a person’s quality of life. It is stressed that, in order to to avoid a re¬sur¬rection of eugenic policies of the past, the development in this field un¬der¬lines the need for continued and strengthen public support to the sick, dis¬abled and mentally retarded.
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