| 1. |
- Koellensperger, Martin, et al.
(författare)
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Red flags for multiple system atrophy
- 2008
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 23:8, s. 1093-1099
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Tidskriftsartikel (refereegranskat)abstract
- The clinical diagnosis Of Multiple system atrophy (MSA) is fraught with difficulty and there are no pathognomonic features to discriminate the parkinsonian variant (MSA-P) from Parkinson's disease (PD). Besides the poor response to levodopa, and the additional presence of pyramidal or cerebellar signs (ataxia) or autonomic failure as major diagnostic criteria, certain other clinical features known as "red flags" or warning signs may raise the clinical suspicion of MSA. To study the diagnostic role of these features in MSA-P versus PD patients, a standardized red flag check list (RFCL) developed by the European MSA Study Group (EMSA-SG) was administered to 57 patients with probable MSA-P and 116 patients with probable PD diagnosed according to established criteria. Those red flags with a specifity over 95% were selected for further analysis. Factor analysis was applied to reduce the number of red flags. The resulting set was then applied to 17 patients with possible MSA-P who on follow-up fulfilled criteria of probable MSA-P. Red flags were grouped into related categories. With two or more of six red flag categories present specificity was 98.3% and sensitivity was 84.2% in our cohort. When applying these criteria to patients with possible MSA-P, 76.5% of them would have been correctly diagnosed as probable MSA-P 15.9 (+/- 7.0) months earlier than with the Consensus criteria alone. We propose a combination of two out of six red flag categories as additional diagnostic criteria for probable MSA-P. (C) 2008 Movement Disorder Society.
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| 2. |
- Apweiler, Rolf, et al.
(författare)
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Approaching clinical proteomics : current state and future fields of application in cellular proteomics
- 2009
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Ingår i: Cytometry. Part A : the journal of the International Society for Analytical Cytology. - : Wiley. - 1552-4922. ; 75A:10, s. 816-832
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Forskningsöversikt (refereegranskat)abstract
- Recent developments in proteomics technology offer new opportunities for clinical applications in hospital or specialized laboratories including the identification of novel biomarkers, monitoring of disease, detecting adverse effects of drugs, and environmental hazards. Advanced spectrometry technologies and the development of new protein array formats have brought these analyses to a standard, which now has the potential to be used in clinical diagnostics. Besides standardization of methodologies and distribution of proteomic data into public databases, the nature of the human body fluid proteome with its high dynamic range in protein concentrations, its quantitation problems, and its extreme complexity present enormous challenges. Molecular cell biology (cytomics) with its link to proteomics is a new fast moving scientific field, which addresses functional cell analysis and bioinformatic approaches to search for novel cellular proteomic biomarkers or their release products into body fluids that provide better insight into the enormous biocomplexity of disease processes and are suitable for patient stratification, therapeutic monitoring, and prediction of prognosis. Experience from studies of in vitro diagnostics and especially in clinical chemistry showed that the majority of errors occurs in the preanalytical phase and the setup of the diagnostic strategy. This is also true for clinical proteomics where similar preanalytical variables such as inter- and intra-assay variability due to biological variations or proteolytical activities in the sample will most likely also influence the results of proteomics studies. However, before complex proteomic analysis can be introduced at a broader level into the clinic, standardization of the preanalytical phase including patient preparation, sample collection, sample preparation, sample storage, measurement, and data analysis is another issue which has to be improved. In this report, we discuss the recent advances and applications that fulfill the criteria for clinical proteomics with the focus on cellular proteomics (cytoproteomics) as related to preanalytical and analytical standardization and to quality control measures required for effective implementation of these technologies and analytes into routine laboratory testing to generate novel actionable health information. It will then be crucial to design and carry out clinical studies that can eventually identify novel clinical diagnostic strategies based on these techniques and validate their impact on clinical decision making.
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| 3. |
- Apweiler, Rolf, et al.
(författare)
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Approaching clinical proteomics : current state and future fields of application in fluid proteomics
- 2009
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Ingår i: Clinical Chemistry and Laboratory Medicine. - 1434-6621 .- 1437-4331. ; 47:6, s. 724-744
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Forskningsöversikt (refereegranskat)abstract
- The field of clinical proteomics offers opportunities to identify new disease biomarkers in body fluids, cells and tissues. These biomarkers can be used in clinical applications for diagnosis, stratification of patients for specific treatment, or therapy monitoring. New protein array formats and improved spectrometry technologies have brought these analyses to a level with potential for use in clinical diagnostics. The nature of the human body fluid proteome with its large dynamic range of protein concentrations presents problems with quantitation. The extreme complexity of the proteome in body fluids presents enormous challenges and requires the establishment of standard operating procedures for handling of specimens, increasing sensitivity for detection and bioinformatical tools for distribution of proteomic data into the public domain. From studies of in vitro diagnostics, especially in clinical chemistry, it is evident that most errors occur in the preanalytical phase and during implementation of the diagnostic strategy. This is also true for clinical proteomics, and especially for fluid proteomics because of the multiple pretreatment processes. These processes include depletion of high-abundance proteins from plasma or enrichment processes for urine where biological variation or differences in proteolytic activities in the sample along with preanalytical variables such as inter- and intra-assay variability will likely influence the results of proteomics studies. However, before proteomic analysis can be introduced at a broader level into the clinical setting, standardization of the preanalytical phase including patient preparation, sample collection, sample preparation, sample storage, measurement and data analysis needs to be improved. In this review, we discuss the recent technological advances and applications that fulfil the criteria for clinical proteomics, with the focus on fluid proteomics. These advances relate to preanalytical factors, analytical standardization and quality-control measures required for effective implementation into routine laboratory testing in order to generate clinically useful information. With new disease biomarker candidates, it will be crucial to design and perform clinical studies that can identify novel diagnostic strategies based on these techniques, and to validate their impact on clinical decision-making.
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| 4. |
- Druker, Brian J., et al.
(författare)
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Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia
- 2006
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 355:23, s. 2408-2417
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The cause of chronic myeloid leukemia (CML) is a constitutively active BCR-ABL tyrosine kinase. Imatinib inhibits this kinase, and in a short-term study was superior to interferon alfa plus cytarabine for newly diagnosed CML in the chronic phase. For 5 years, we followed patients with CML who received imatinib as initial therapy. METHODS: We randomly assigned 553 patients to receive imatinib and 553 to receive interferon alfa plus cytarabine and then evaluated them for overall and event-free survival; progression to accelerated-phase CML or blast crisis; hematologic, cytogenetic, and molecular responses; and adverse events. RESULTS: The median follow-up was 60 months. Kaplan-Meier estimates of cumulative best rates of complete cytogenetic response among patients receiving imatinib were 69% by 12 months and 87% by 60 months. An estimated 7% of patients progressed to accelerated-phase CML or blast crisis, and the estimated overall survival of patients who received imatinib as initial therapy was 89% at 60 months. Patients who had a complete cytogenetic response or in whom levels of BCR-ABL transcripts had fallen by at least 3 log had a significantly lower risk of disease progression than did patients without a complete cytogenetic response (P<0.001). Grade 3 or 4 adverse events diminished over time, and there was no clinically significant change in the profile of adverse events. CONCLUSIONS: After 5 years of follow-up, continuous treatment of chronic-phase CML with imatinib as initial therapy was found to induce durable responses in a high proportion of patients. (ClinicalTrials.gov number, NCT00006343 [ClinicalTrials.gov].)
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| 5. |
- Noll, Gregor, et al.
(författare)
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The asylum system, migrant networks and the Informal labour market
- 2008
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Ingår i: Swedish Studies in European Law. - 9781841136561 ; 2
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Governments attempting to regulate labour markets and control immigration are confronted with difficult questions. In the past, there was general agreement that the asylum system should not be exploited as a side entrance to the labour market. The two systems—asylum and labour market—were to be planned and maintained separately. But if migration is a prerequisite for asylum, does not increasingly stiffer migration control block escape for those under persecution? Prices for smuggling go up, and smugglers seek new routes, yet irregular migration continues, and the informal labour market flourishes. Here we must ask an irreverent question: is there any point in having both systems? And can the crux of the matter be that both are repeatedly branded as an ‘illegal’ phenomena which must be ‘battled’ like enemies? This contribution asks whether the asylum system a way to regulate the informal labour market within the EU?
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| 6. |
- Rich, Rebecca L., et al.
(författare)
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A global benchmark study using affinity-based biosensors
- 2009
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Ingår i: Analytical Biochemistry. - : Elsevier BV. - 0003-2697 .- 1096-0309. ; 386:2, s. 194-216
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Tidskriftsartikel (refereegranskat)abstract
- To explore the variability in biosensor studies, 150 participants from 20 countries were given the same protein samples and asked to determine kinetic rate constants for the interaction. We chose a protein system that was amenable to analysis using different biosensor platforms as well as by users of different expertise levels. The two proteins (a 50-kDa Fab and a 60-kDa glutathione S-transferase [GST] antigen) form a relatively high-affinity complex, so participants needed to optimize several experimental parameters, including ligand immobilization and regeneration conditions as well as analyte concentrations and injection/dissociation times. Although most participants collected binding responses that could be fit to yield kinetic parameters, the quality of a few data sets could have been improved by optimizing the assay design. Once these outliers were removed, the average reported affinity across the remaining panel of participants was 620 pM with a standard deviation of 980 pM. These results demonstrate that when this biosensor assay was designed and executed appropriately, the reported rate constants were consistent, and independent of which protein was immobilized and which biosensor was used.
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| 7. |
- Richards, Stephen, et al.
(författare)
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The genome of the model beetle and pest Tribolium castaneum.
- 2008
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Ingår i: Nature. - 1476-4687. ; 452:7190, s. 949-55
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Tidskriftsartikel (refereegranskat)abstract
- Tribolium castaneum is a representative of earth’s most numerous eukaryotic order, a powerful model organism for the study of generalized insect development, and also an important pest of stored agricultural products. We describe its genome sequence here. This omnivorous beetle has evolved an ability to interact with a diverse chemical environment as evidenced by large expansions in odorant and gustatory receptors, as well as p450 and other detoxification enzymes. Developmental patterns in Tribolium are more representative of other arthropods than those found in Drosophila, a fact represented in gene content and function. For one, Tribolium has retained more ancestral genes involved in cell-cell communication than Drosophila, and some are expressed in the growth zone crucial for axial elongation in short germ development. Systemic RNAi in T. castaneum appears to use mechanisms distinct from those found in C. elegans, but nevertheless offers similar power for the elucidation of gene function and identification of targets for selective insect control.
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| 8. |
- Wagner, Thomas Gregor, 1975-
(författare)
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Die Seuchen der Kreuzzüge : Krankheit und Krankenpflege auf den bewaffneten Pilgerfahrten ins Heiligen Land
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Die Kreuzzugspredigt Papst Urbans II. am 27. November 1095 hatte Volksmassen in Bewegung versetzt. Zwei Jahrhunderte hindurch brachen christliche Heere zur Befreiung Jerusalems auf, doch nur ein Bruchteil der „bewaffneten Pilger“ gelangte ins Heilige Land. Doch waren es nicht die Schlachten, die am meisten Opfer forderten. Weitaus schlimmer als die sarazenischen Krummsäbel wüteten Hunger und Seuchen unter den Kreuzfahrern. Nach heutigen Schätzungen überlebte nur jeder Fünfte. Die vorliegende Studie bietet Einblick in die medizinische Versorgung und die Lebensverhältnisse in den Feldlagern der Kreuzfahrer. Die Analyse historischer Seuchenbeschreibungen zeigt, wie die zeitgenössischen Berichterstatter todbringende Epidemien wahrnahmen, wie sie Krankheitsverläufe darstellten und deuteten. In den mittelalterlichen Kreuzzugschroniken begegnen uns zudem die damals vorherrschenden Körper- und Krankheitskonzepte. Und nicht zuletzt werden uns durch die Betrachtung von Krankheit, Leiden und Tod im Umfeld der Kreuzzüge tragische menschliche Schicksale vor Augen geführt, welche uns die brutale Körperlichkeit einer religiös-spirituellen Massenbewegung aufzeigen.
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| 9. |
- Wagner, Thomas Gregor, 1975-, et al.
(författare)
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Medieval Christian invocation inscriptions on sword blades
- 2009
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Ingår i: Waffen- und Kostümkunde. - Sonnefeld : Louis Hofmann-Druck. - 0042-9945. ; 51:1, s. 11-52
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Tidskriftsartikel (refereegranskat)abstract
- The following article presents and discusses four high medieval swords (12th to 13th centuries) deriving from the Uppland- (Uppsala) or the Värmland-region (Karlstad) in Sweden. Two of the Uppsala-swords were the main part of an exhibition (entitled “Svärd från Sveriges turbulenta barndom” or “Swords from Sweden’s turbulent childhood”) that was open to public from July 2007 to January 2008 in the Museum Gustavianum in Uppsala (Fyris UMF/B 74 and 78). The Värmland-sword (Nr. 17001-34945) is kept in the Värmlands Museum in Karlstad. The forth sword to be included was found near the town hall in Uppsala, but it is now kept in the Historical Museum in Stockholm. The archaeological and typological data of all the swords are presented here for the first time.The main focal point of the article is the examination of the hitherto unpublished epigraphic evidence, namely the metal inlay, gold and silver inscriptions on the blades. A comparison with specimens in Germany (Deutsches Historisches Museum, Zeughaussammlung Berlin) revealed a close relationship between the blade-inscriptions on the Swedish and the German swords), potentially even a provenance from the same workshop. By analyzing the letter sequences it was possible to categorize the inscriptions in three different subgroups (DIC-, SDX- and INNOMINEDOMINI-group). Although a definite reading could not be given, the intense examination brought to light arguments that led to the interpretation as religious invocations, probably addressed to Jesus Christ himself.
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| 10. |
- Wagner, Thomas Gregor, 1975-
(författare)
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Rex incidit in aegritudinem, quam Arnaldiam vocant : Untersuchungen zur „aegritudo Arnaldia“ – der rätselhaften Erkrankung, welche die Könige Richard Löwenherz und Philipp II. August während der Belagerung von Akkon im Jahre 1191 befiel
- 2008
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Ingår i: Fachprosaforschung - Grenzueberschreitungen. - Baden Baden : Deutscher Wissenschafts-Verlag. - 1863-6780. ; 2/3, s. 43-56
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Historical diagnosis is a problematic, challenging, but nevertheless fascinating field – especially in the period of Middle Ages. The depiction of sickness and disease in the contemporary source material is often intermittent or follows stereotype description-patterns that do not allow an accurate identification. The chroniclers furthermore tend to moralize illness by interpreting it as a sign for impurity or sin. In most cases the retrospective analysis of medieval disease patterns can therefore only evolve possible settings and estimate their plausibility. The following treatise is a description of the „Aegritudo Arnaldia“ – the infectious disease Richard the Lion Heart and Philipp II. August of France came down with during the siege of Acre in June 1191. The symptoms handed down in both English and French sources draw a mysterious clinical picture which is characterized by high fever, ague and the loss of hair, nails and skin.
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