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Implementation of pharmacokinetic guided dosing of desmopressin and Von Willebrand factor containing concentrates in Von Willebrand disease
No full textThe aim of this thesis is to provide insight into the mechanisms underlying the inter- and intra-individual variability in response to desmopressin and VWF containing concentrates in patients with Von Willebrand disease (VWD) and low Von Willebrand Factor (VWF) by application of population PK modelling
Therapeutic assessment in patients with personality disorders
No full textThe degree to which clinical assessment has treatment utility (i.e. enhances meaningful outcomes for patients) is a topic of ongoing controversy. Empirical data from well-designed studies on this issue are quite scarce. However, accumulating evidence suggests that Therapeutic Assessment (TA) can be an effective intervention in a diversity of populations (Aschieri, De Saeger, & Durosini, 2015). TA is an assessment-driven therapeutic intervention that helps clients to develop new representation of themselves and the world (Finn, 1996). The full model of TA was never tested and most research did not conduct randomized comparisons and/ or were of low sample size. Moreover, the efficacy of TA in clients with Personality Disorders (PD) has not yet been examined. We present a conceptual analysis suggesting that features of TA and the specific clinical needs of clients with PD are well matched. In short, the main objective of this thesis was to conduct a stringent test of the treatment utility of the full model of TA in patients with personality disorder. Part A of this thesis provides a general description of the TA model and provides a clinical case example. Part B reports on a Randomized Controlled Trial (RCT). To get a deeper understanding of the findings of the RCT we conducted a qualitative follow-up study asking these clients what they deemed memorable about their TA experience
Clinical, pathological, biochemical and genomic characteristics of poorly differentiated thyroid cancer
No full textThis is a comprehensive study of one of the largest cohort of poorly differentiated thyroid carcinoma (PDTC) patients reported in the literature, diagnosed by criteria of proliferative grading and treated surgically at a tertiary care academic center, with or without adjuvant therapy. The main objectives were: to report on clinicopathological, biochemical and genomic characteristics of PDTC patients, to correlate those characteristics with outcome and to report on the patterns of treatment failure. PDTC patients presented with adverse clinicopathological characteristics of thyroid cancer: older age, male gender, local spread and tendency for distant spread. pT4a and M1 remained significant predictors of worse outcome on multivariate analysis. Undetectable Tg after initial treatment of PDTC patients can predict low risk of recurrence, nevertheless a close follow-up is needed due to heterogeneity of PDTC. Initial adequate surgery can achieve satisfactory locoregional control, however distant metastases represent the major cause of cause-specific deaths. By using ultra deep next-generation sequencing, important biomarkers for aggressive behavior of PDTC were identified. Comparison between fatal and nonfatal cases of PDTC revealed that fatal PDTC show a higher frequency of mutations in: TERT promoter, MED12, RBM10, BRAF, HRAS, TP53, ATM and EIF1AX. In addition chromosomal 1q gains are the most common arm level alterations in PDTC and those patients show worse survival rates. We anticipate that these insights into PDTC biology will contribute to the development of standardized clinical guidelines and development of effective targeted therapies in order to improve the outcomes in patients with PDTC
The human figure as method : study, sculpture and sculptors in the Academie Royale de Peinture et de Sculpture (1725-1765)
No full textCreatine kinase and cardiovascular disease
No full textDit proefschrift onderzoekt de rol van creatine kinase (CK) in cardiovasculaire ziekten. CK is een belangrijk enzym in het energie metabolisme van de cel door het katalyseren van het chemische evenwicht:creatinefosfaat + adenosinedifosfaat (ADP) ↔ creatine + adenosinetrifosfaat (ATP).Door het faciliteren van het cellulaire energie metabolisme bevordert CK de contractiliteit van o.a. skeletspieren, de hartspier en gladde spiercellen rondom vaten. Daarnaast wordt ook gedacht dat het de zoutretentie in de nier, tevens een energie consumerend proces, bevordert. Een hoge CK activiteit vergroot hierdoor de kans op hoge bloeddruk.Naast het intracellulaire effect van CK onderzoeken we het effect van het CK dat uit de cel is gelekt en actief is in de bloedbaan (het plasma). Een hoge plasma CK activiteit remt, door het wegvangen van ADP, de bloedplaatjesactivatie en -aggregatie. Gezien het feit dat geactiveerde bloedplaatjes tevens een belangrijke ondersteunende functie hebben in de secundaire hemostase, onderzoeken we ook of plasma CK invloed heeft op de secundaire hemostase.Allereerst wordt in deel I onderzocht of beïnvloeding van de CK activiteit een bloeddrukverlagend effect zou kunnen hebben en dus een mogelijke rol binnen de behandeling van hypertensie. Deel II beschrijft de associatie tussen CK en bloeddruk tijdens en na de zwangerschap. Tevens bestuderen we in dit deel de associatie tussen CK en hypertensieve zwangerschapsaandoeningen. De invloed van CK op de primaire en secundaire hemostase wordt in het derde deel onderzocht door middel van zowel een in vitro studie als een grote populatie studie
Clinical applications of ultrasound examination in the assessment of bone lesions of the jaws
No full textUltrasound examination is a non-invasive real-time imaging modality that has been used in many fields of medicine for more than 50 years. This thesis aimed to evaluate the clinical applications of ultrasound examination to manage various intraosseous lesions affecting the jawbones. The results of the present thesis demonstrated that ultrasound imaging provided reliable information on the content of lesions within the mandible and maxillary bones, with histopathological examination as a gold standard. Furthermore, the diagnostic ability of ultrasound showed its importance when the clinician was struggling to differentially diagnose lesions. The reliability of real-time ultrasound examination was confirmed in the management of complications of infective jaw lesions, since the technique could detect and trace the route of pus drainage from periapical lesions. The present work also demonstrated that, despite the limitations addressed in previous scientific literature, intra-osseous lesions in the jaws can be visualized using ultrasound in a predictable manner, independent of the diameter, thickness, and presence/absence of perforation in the cortical plate. In addition, the findings of the present thesis suggest that echography can be used to predict the outcome of both surgical and non-surgical treatment of bone lesions, as well as to monitor the long-term healing of such lesions