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Alegre, Melissa Marie. "Thymidine Kinase 1: Diagnostic and Prognostic Significance in Malignancy." BYU ScholarsArchive, 2013. https://scholarsarchive.byu.edu/etd/4049.
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Thymidine kinase 1 (TK1) is a cancer biomarker which has diagnostic and prognostic potential in a variety of malignancies. TK1 is significantly elevated in the serum and tumor tissue of most malignancies. This increase in TK1 can be detected in the very early stages of malignancy, including in pre-malignant disease with an increased risk for progression. Several studies have demonstrated that elevated TK1 is found in serum months before any clinical symptoms of malignancy. It has also been demonstrated that TK1 is elevated months before clinical recurrence of malignancy. This work first sought to demonstrate the early nature of TK1 expression in breast tumor tissue and pre-malignant tissue. We found that TK1 is elevated in breast hyperplasia tissue and breast carcinoma tissue. In this study we also identified some cases of ‘normal’ tumor margins (considered normal by current pathological standards) which also had elevated TK1 expression. Conversely, true normal breast tissue from noncancerous individuals had no reported elevation in TK1 expression. This study illustrated that TK1 is elevated in pre-malignant breast hyperplasia tissue, as well as some 'normal' tumor margins. TK1 expression was significantly elevated in lung, prostate, colon, esophagus, stomach, liver, and kidney tissues. This work further investigated TK1 expression in a variety of malignant tissue including the two leading causes of cancer mortality in men: lung and prostate cancer. In our study, TK1 was significantly elevated in lung and prostate cancer but not significantly elevated in prostate hyperplasia tissue. TK1 expression also increased with increasing grade in prostate carcinoma tissue. Overall, this work demonstrated that TK1 is a good universal marker of malignancy and is elevated in early cancer development. Despite the potential for TK1 as both a screening and monitoring treatment tool, there have been significant challenges associated with developing a clinically relevant method of TK1 detection. This work proposes one clinically relevant method of detection, namely a TK1 ELISA. Using preoperable lung cancer patients and normal controls, we developed a sensitive and specific ELISA which shows highly statistically significant differences in serum TK1 levels between stage 1 and stage 2 lung cancer compared with normal controls. In fact, this TK1 ELISA is more sensitive and accurate than the traditional TK radioassay, which was unable to detect differences in TK1 between early stage lung cancer and normal patients. Although elevated TK1 is not lung cancer specific, we reported significantly elevated TK1 levels in lung cancer sputum. Screening of sputum and serum for TK1 may be one method for the early detection of lung cancer. Overall, we report TK1 has promising diagnostic potential in a variety of malignancies. We also propose one sensitive and specific method to detect TK1 levels which may easily be adapted to meet current clinical applications. We hope this work will help propel TK1 forward into clinical view in the coming years.
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MEGHA, T., A. NERI, S. CARUSO, M. ONORATI, F. ROVIELLO, P. TOSI, and VALERIA MALAGNINO. "Traditional and new diagnostic and prognostic markers in breast cancer." Doctoral thesis, Università di Siena, 2017. http://hdl.handle.net/11365/1012970.
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Despite the constant progress on the understanding of the molecular bases of cancer, there is still the need to identify novel prognostic and predictive markers aimed at improving diagnosis and, at the same time, designing a more targeted therapeutic approach. For this to be achieved, we have to take into consideration the biological heterogeneity of each tumor that explains different responses to standard therapies harbored by different patients within the same tumor stage and histological type.
Such a combined approach does not apply to improving classification and prognosis of breast cancer only, but it is widely applicable to a better understanding and treatment of all cancers. Nevertheless, it is also crucial to bare in mind that cancer is a genetic disease and molecular analyses aimed at unravelling genetic make-up of tumors are of extreme importance. However, the contribution of the environment in the development of a neoplastic disease should not be ignored, as this would also provide useful insights for cancer prevention. Exposure to harmful substances (i.e. X-rays, UV-light, carcinogens just to list some examples) and to pathogens which might be endemic in some areas could also contribute to triggering genetic alterations whose accumulation may result in malignant transformation, and should not be ignored when trying to understand the etiology of certain tumors.
The aim of this thesis is to provide evidence of how novel genetic markers may contribute to a better classification and diagnosis of cancer, using as examples studies conducted on breast cancer and lymphoma. Also, reactivation of the Epstein-Barr virus due to exposure of unfavorable environmental conditions is provided in another study, to highlight the tremendous importance of the environment in the development of cancer, which is too often dismissed in both the anamnesis of cancer patients and in research studies.
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BARONE, ELISA. "Overexpressed genes in malignant pleural mesothelioma: possible role in tumorigenesis and evaluation of their use as a prognostic marker." Doctoral thesis, Università di Siena, 2017. http://hdl.handle.net/11365/1005849.
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Malignant Pleural Mesothelioma (MPM) is a very aggressive cancer poorly responsive to current therapies. The prognosis is very poor as the development of MPM leads to a median survival of less than one year from the time of diagnosis (Bertino et al. 2009). Moreover, the rapidly growing nature of this cancer, the non-specific onset of symptoms and the lack of an accurate biomarker do not lead to a sufficiently early diagnosis for a radical treatment of the disease. Thus, the identification of novel diagnostic and prognostic biomarkers and therapeutic targets is needed. The knowledge of the genes involved in the triggering/progression of MPM is still limited. In recent years a number of aberrantly expressed genes were suggested, but with a poor consistency among studies. To identify the relevant genes potentially involved in MPM, recently, our group carried out an extensive literature review focused on transcriptome studies whose results were intersected with those from a data mining approach (Melaiu et al. 2012). The results underwent to validation on MPM tissues and cell lines (Melaiu et al. 2015). The study led to the identification of a group of 21 deregulated genes in MPM. Among the 21 genes identified we focused our attention on those up-regulated in MPM tissues and at least in one MPM cell line (i.e. THBS2, CCNO, CFB, TIMP3, SULF1, PDGFRB, ASS1, SOD1, RAN, CDH11, EIF4G1). In addition, we made an extensive literature search to identify the most promising novel diagnostic and therapeutic target for MPM and we undertook the study of IMP3 (Hanley et al.2008; Ikeda et al. 2010; Ikeda et al. 2011; Shi et al.2011; Lee et al. 2013; Okazaki et al. 2013; Minato et a. 2014) , MCT4 (Mogi et al. 2013), MCT1 (Mogi et al. 2013), BSG (Pinheiro et al. 2012) and CAIX (Ramsey et al. 2012; Capkova et al. 2014).
In order to investigate the role of these genes in the carcinogenesis of MPM we performed a phenotypic screening of five MPM cell lines (Mero14, Mero25, IstMes2, NCI-H28, REN) and one non-malignant mesothelial cell line (Met5A) following gene-silencing. We analysed the changes in the proliferation rate, in the caspase3-7 activity, in the migration ability, in the colony formation ability, in the level of senescence and in the cell cycle after transient siRNA transfections.
The RNAi screening highlighted a role in MPM malignant phenotype for ASS1, CDH11, EIF4G1, IMP3, MCT4, PDGFRB, RAN, SOD1, SULF1, THBS2, TIMP3.
Moreover, we evaluated the potential prognostic role of THBS2, CDH11, ITGA4, MCT4, MCT1, BSG and CAIX through a tissue microarray (TMA) immunohistochemistry on a series of 135 MPM samples. None of the target analysed showed a statistical significant association, after multiple correction, between protein expression and the overall survival. The weak staining of THBS2 and the negative staining of MCT4 on six normal pleura samples compared to MPM tissues prompted us to further investigate on protein expression levels: we increased the analysis of protein expression to 15 normal pleura samples.
These results highlights the role of a group of genes, overexpressed in MPM, in the carcinogenetic process suggesting potential novel therapeutic approaches for the treatment of MPM.
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Al-Khalili, Faris. "Coronary heart disease in women : diagnostic and prognostic markers /." Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-4092-4/.
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Abou, Farha Khalid Mohamed Mohamed. "Diagnostic and prognostic value of laminin as a biochemical and a histological marker in human bladder carcinoma." Maastricht : Maastricht : Universitaire Pers Maastricht ; University Library, Maastricht University [Host], 1992. http://arno.unimaas.nl/show.cgi?fid=6506.
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Carpio, Ricardo, Juan Zapata, Eberhard Spanuth, and Georg Hess. "Utility of presepsin (sCD14-ST) as a diagnostic and prognostic marker of sepsis in the emergency department." Elsevier B.V, 2015. http://hdl.handle.net/10757/576944.
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Presepsin (PSEP) is released during infectious diseases and can be detected in the blood. PSEP has shown promising results as sepsis marker. We examined the diagnostic and prognostic validity of PSEP in patients suspicious of sepsis on admission in the emergency department (ED). Methods One hundred twenty three patients with signs of SIRS and/or sepsis and 123 healthy individuals were enrolled. PSEP was determined on admission, after 8, 24 and 72 h. Results Mean PSEP concentrations of the control group and the patient group were 130 and 1945 pg/ml. PSEP differed between SIRS, sepsis, severe sepsis and septic shock and showed strong association with 30-day mortality ranging from 10.3% in the 1st to 32.1% in the 4th quartile. The ROC curve analyses revealed an AUC value of 0.743. Combined assessment of PSEP and MEDS score increased the AUC up to 0.878 demonstrating the close relationship with outcome. Based on the PSEP values in the different severity degrees, decision thresholds for risk stratification were established. The course of PSEP during the first 72 h was associated with effectiveness of treatment and outcome. Conclusions PSEP allowed outcome prediction already on admission to a similar degree as the clinical scores MEDS and APACHE II. Combination of PSEP with MEDS score improved the discriminatory power for outcome prediction.Our study has been supported by Mitsubishi Chemical Europe through providing the PSEP reagents free of charge. Dr. Carpio has received speaker honoraria from Mitsubishi Chemical Europe. DIAneering – Diagnostics Engineering & Research consulted to Axis Shield Diagnostics, Mitsubishi Chemical Europe, Radiometer, Roche Diagnostics, Shanghai Kehua Bio-engineering. No potential conflict of interest to this paper was reported
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Danner, Maria [Verfasser], and Elisabeth [Akademischer Betreuer] Pollerberg. "Marker-free T cell phenotyping - towards a label-free diagnostic and prognostic platform / Maria Danner ; Betreuer: Elisabeth Pollerberg." Heidelberg : Universitätsbibliothek Heidelberg, 2017. http://d-nb.info/1178008258/34.
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Danner, Maria [Verfasser], and G. Elizabeth [Akademischer Betreuer] Pollerberg. "Marker-free T cell phenotyping - towards a label-free diagnostic and prognostic platform / Maria Danner ; Betreuer: Elisabeth Pollerberg." Heidelberg : Universitätsbibliothek Heidelberg, 2017. http://nbn-resolving.de/urn:nbn:de:bsz:16-heidok-222400.
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Gaigneaux, Anthoula. "Determination of diagnostic and prognostic markers in varied tumoral pathologies by ATR-FTIR spectroscopy." Doctoral thesis, Universite Libre de Bruxelles, 2004. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/211150.
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Nicol, Lisa Margaret. "Diagnostic and prognostic value of current phenotyping methods and novel molecular markers in idiopathic pulmonary fibrosis." Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/33098.
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Background Idiopathic pulmonary fibrosis (IPF) is a devastating form of chronic lung injury of unknown aetiology characterised by progressive lung scarring. A diagnosis of definite IPF requires High Resolution Computed Tomography (HRCT) appearances indicative of usual interstitial pneumonia (UIP), or in patients with 'possible UIP' CT appearances, histological confirmation of UIP. However the proportion of such patients that undergo SLB varies, perhaps due to a perception of risk of biopsy and additive diagnostic value of biopsy in individual patients. We hypothesised that an underlying UIP pathological pattern may result in increased risk of death and aimed to explore this by comparing the risk of SLB in suspected idiopathic interstitial pneumonia, stratified according to HRCT appearance. Additionally we sought to determine the positive-predictive value of biopsy to diagnose IPF in patients with 'possible UIP HRCT' in our population. In patients with possible UIP who are not biopsied, the clinical value of bronchoalveolar lavage (BAL) is uncertain. We aimed to prospectively study the diagnostic and prognostic value of BAL differential cell count (DCC) in suspected IPF and determine the feasibility of repeat BAL and the relationship between DCC and disease progression in two successive BALs. We hypothesised that BAL DCC between definite and possible IPF was different and that baseline DCC and change in BAL DCC predicted disease progression. Alveolar macrophages (AMs) are an integral part of the lung's reparative mechanism following injury, however in IPF they contribute to pathogenesis by releasing pro-fibrotic mediators promoting fibroblast proliferation and collagen deposition. Expansion of novel subpopulations of pulmonary monocyte-like cells (PMLCs) has been reported in inflammatory lung disease. We hypothesised that a distinct AM polarisation phenotype would be associated with disease progression. We aimed to perform detailed phenotyping of AM and PMLCs in BAL in IPF patients. Several prognostic scoring systems and biomarkers have been described to predict disease progression in IPF but most were derived from clinical trial patients or tertiary referral centres and none have been validated in separate cohorts. We aimed to identify a predictive tool for disease progression utilising physiological, HRCT and serum biomarkers in a unique population of incident treatment naïve IPF patients. Methods Between 01/01/07 and 31/12/13, 611 consecutive incident patients with suspected idiopathic interstitial pneumonia (IIP) presented to the Edinburgh lung fibrosis clinic. Of these patients 222 underwent video-assisted thoracoscopic lung biopsy and histological pattern was determined according to ATS/ERS criteria. Post-operative mortality and complication rates were examined. Fewer than 2% received IPF-directed therapy and less than 1% of the cohort were lost to follow-up. Disease progression was defined as death or ≥10% decline in VC within 12 months of BAL. Cells were obtained by BAL and a panel of monoclonal antibodies; CD14, CD16, CD206, CD71, CD163, CD3, CD4, CD8 and HLA-DR were used to quantify and selectively characterise AMs, resident PMLCs, inducible PMLCs, neutrophils and CD4+/CD8+ T-cells using flow cytometry. Classical, intermediate and non-classical monocyte subsets were also quantified in peripheral blood. Potential biomarkers (n=16) were pre-selected from either previously published studies of IPF biomarkers or our hypothesis-driven profiling. Linear logistic regression was used on each predictor separately to assess its importance in terms of p-value of the associated weight, and the top two variables were used to learn a decision tree. Results Based on the 2011 ATS/ERS criteria, 87 patients were categorised as 'definite UIP', of whom 3 underwent SLB for clinical indications. IPF was confirmed in all 3 patients based on 2013 ATS/ERS/JRS/ALAT diagnostic criteria. 222 patients were diagnosed with 'possible UIP'; 55 underwent SLB, IPF was subsequently diagnosed in 37 patients, 4 were diagnosed with 'probable IPF' and 14 were considered 'not IPF'. In this group, 30 patients were aged 65 years or over and 25/30 (83%) had UIP on biopsy. 306 patients had HRCTs deemed 'inconsistent with UIP', SLB was performed in 168 patients. Post6 operative 30-day mortality was 2.2% overall, and 7.3% in the 'possible UIP' HRCT group. Patients with 'definite IPF' based on HRCT and SLB appearances had significantly better outcomes than patients with 'definite UIP' on HRCT alone (P=0.008, HR 0.44 (95% CI 0.240 to 0.812)). BAL DCC was not different between definite and possible UIP groups, but there were significant differences with the inconsistent with UIP group. In the 12 months following BAL, 33.3% (n=7/21) of patients in the definite UIP group and 29.5% (n=18/61) in the possible UIP group had progressed. There were no significant differences in BAL DCC between progressor and non-progressor groups. Mortality in patients with suspected IPF and a BAL DCC consistent with IPF was no different to those with a DCC inconsistent with IPF (P=0.425, HR 1.590 (95% CI 0.502 to 4.967)). There was no difference in disease progression in either group (P=0.885, HR 1.081 (95% CI 0.376 to 3.106)). There was no statistically significant difference in BAL DCC at 0 and 12 months in either group. There was no significant change in DCC between 0 and 12 month BALs between progressors and non-progressors. Repeat BAL was well tolerated in almost all patients. There was 1 death within 1 month of a first BAL and 1 death within 1 month of a second BAL; both were considered 'probably procedure-related'. AM CD163 and CD71 (transferrin receptor) expression were significantly different between groups (P < 0.0001), with significant increases in the IPF group vs non fibrotic ILD (P < 0.0001) and controls (P < 0.0001 and P < 0.001 respectively). CD71 expression was also significantly increased in the IPF progressor vs non-progressor group (P < 0.0001) and patients with high CD71 expression had significantly poorer survival than the CD71low group (P=0.040, median survival 40.5 and 75.6 months respectively). CD206 (mannose receptor) expression was also significantly higher in the IPF progressor vs non-progressor group (P=0.034). There were no differences in baseline BAL neutrophil, eosinophil or lymphocyte percentages between IPF progressor or non-progressor groups. The percentage of rPMLCs was significantly increased in BAL fluid cells of IPF patients compared to those with non-fibrotic ILD (P < 0.0001) and healthy controls (P < 0.05). Baseline rPMLC percentage was significantly higher in IPF progressors vs IPF non-progressors (P=0.011). Baseline BAL iPMLC:rPMLC ratio was also significantly different between IPF progressor and non-progressor groups (P=0.011). Disease progression was confidently predicted by a combination of clinical and serological variables. In our cohort we identified a predictive tool based on two key parameters, one a measure of lung function and one a single serum biomarker. Both parameters were entered into a decision tree, and when applied to our cohort yielded a sensitivity of 86.4%, specificity of 92.3%, positive predictive value of 90.5% and negative predictive value of 88.9%. We also applied previously reported predictive tools such as the GAP Index, du Bois score and CPI Index to the Edinburgh IPF cohort. Conclusions SLB can be of value in the diagnosis of ILD, however perhaps due to the perceived risks associated with the procedure, only a small percentage of patients undergo SLB despite recommendations that patients have histological confirmation of the diagnosis. Advanced age is a strong predictor for IPF, and in our cohort 83% of patients aged over 65 years with 'possible UIP' HRCT appearances, had UIP on biopsy. BAL and repeat BAL in IPF is feasible and safe (< 1.5% mortality). Of those that underwent repeat BAL, disease progression was not associated with a change in DCC. However, 22% of lavaged patients died or were deemed too frail to undergo a second procedure at 12 months. These data emphasise the importance of BAL in identifying a novel human AM polarisation phenotype in IPF. Our data suggests there is a distinct relationship between AM subtypes, cell-surface expression markers, PMLC subpopulations and disease progression in IPF. This may be utilised to investigate new targets for future therapeutic strategies.Disease progression in IPF can be predicted by a combination of clinical variables and serum biomarker profiling. We have identified a unique prediction model, when applied to our locally referred, incident, treatment naïve cohort can confidently predict disease progression in IPF. IPF is a heterogeneous disease and there is a definite clinical need to identify 'personalised' prognostic biomarkers which may in turn lead to novel targets and the advent of personalised medicines.
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RUGGERONE, BEATRICE. "OXIDATIVE-ANTIOXIDATIVE COMPOUNDS AND LIPID PARAMETERS AS POTENTIAL DIAGNOSTIC AND PROGNOSTIC MARKERS IN ANIMALS WITH SIRS." Doctoral thesis, Università degli Studi di Milano, 2019. http://hdl.handle.net/2434/619500.
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Nowadays in veterinary medicine the discrimination between an inflammatory status and a systemic inflammatory response syndrome (SIRS) sometimes related to an infectious disease and with a poorer prognosis, could be difficult, both for the clinicians and the clinical pathologists. An early diagnosis would permit to avoid unnecessary use of antibiotics (mainly to contain the problem of antibiotic resistance) and to establish an appropriate monitoring plan.
The aim of the two first described works was to validate in horses the Paraoxonase-1 (PON-1), a negative acute phase protein already used in dogs; 120 healthy horses of different sex, age and breed were enrolled; then, this protein was evaluated as a possible diagnostic and prognostic markers of SIRS in this species; PON-1 did not seem to be useful to this aim. The prognostic value was not evaluable because of the small amount of survivors in the SIRS group that did not permit a serial evaluation of PON-1 values.
The second part of the thesis is about the Protein Carbonyls (PCOs), that are already used as sepsis markers in humans; a Western Blotting method was initially validated to detect PCOs in canine serum from healthy patients; then, a spectrophotometric method, that could be cheaper and faster than the first one, was employed. With this method, serum from healthy dogs and from dogs with septic or non-septic inflammation was used to measure PCOs. Results between groups were compared to evaluate if PCOs could be considered as possible diagnostic markers of sepsis in association with PON-1 and C-reactive protein (CRP). This marker seemed to be useful to distinguish dogs with sepsis from dogs with sterile inflammation or healthy, but not to give prognostic information.
An increase in the amount of the enrolled dogs would consent to enforce the hypothesis that PCOs could become a reliable support to diagnose sepsis.
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Ambrose, Jason H. "Evaluation of a microsphere-based immunoassay (MIA) in measuring diagnostic and prognostic markers of dengue virus infection." Scholar Commons, 2017. http://scholarcommons.usf.edu/etd/6995.
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Infections with dengue viruses (DENV) constitute both a global problem as well as locally in Florida. DENV comprise four distinct serotypes of single-stranded RNA viruses and belong to the family Flaviviridae. DENV are among the most medically important arboviruses in the world and cases may currently exceed 400 million per annum. Additionally, dengue established its first recorded endemic transmission cycle in the state of Florida in over a half century, first within the Florida Keys during 2009-10 followed by an unrelated outbreak in Martin County in 2013. The clinical profile of DENV infections ranges from a mild febrile illness to severe illness including hemorrhaging and/or shock, occasionally leading to death. Asymptomatic and mild cases also play a role in maintaining transmission cycles. The early diagnosis and management of patients at the clinical level have both proven to be major obstacles in the control of DENV and are important at both the individual and community levels. Individually, the proper management of patients that will progress to severe illness demands that they are identified in order to receive supportive treatment and mitigate associated morbidity and mortality. At the community level, early diagnosis may reduce transmission by limiting the possibility of vector contact with viremic individuals. Early diagnosis is dependent on the detection of viral markers, while a number of host factors may inform prognosis. The microsphere-based immunoassay (MIA) is capable of detecting up to 100 different targets in a single sample and therefore would be useful as a single assay for determining both. This study attempted to develop a diagnostic and prognostic MIA using the DENV NS1 glycoprotein and 5 host markers as targets. For the purposes of DENV NS1 detection in MIA, a set of monoclonal antibodies (mAbs) were subjected to immunoprecipitation and/or Western blot analysis in order to determine immunoreactivity. Two mAbs, 3A5.4 and 3D1.4, were chosen for use in MIA as a capture antibody and a detection antibody, respectively, and the results compared to a commercially available DENV NS1 ELISA. The 5 markers chosen for MIA trials included GM-CSF, IFN-γ, IP-10, IL-10, and MCP-1 and were selected from a panel of 27 markers screened initially in two in vitro models of DENV infection in addition to serum samples. The two cell lines investigated were HPMEC ST1.6R and u937 as both are thought to play important roles in models of DENV pathogenesis. The results of the DENV NS1 detection MIA were initially promising but were ultimately unsuccessful. When measuring host markers in the MIA, results pointed towards certain profiles that may be of future use. IL-10 was found to be elevated in a statistically significant manner in DENV qRT-PCR+ samples (p=0.035) when compared to negative sera. MCP-1 elevation was found to be of borderline significance (p=0.058). Other potential markers based on the results reported here include IP-10, IL-6, IL-8, VEGF, and RANTES. The ultimate goal of measuring host markers is to gain the ability to differentiate patients that will progress to severe illness from those that will recover. In conclusion, despite the failure of the MIA to detect DENV NS1 in human sera, our results in determining host markers and developments leading to successful DENV NS1 detection ELISAs elsewhere lead us to believe that this approach remains promising. Major drawbacks of this study included the lack of samples from patients that experienced severe DENV illness as a comparative group in addition to small sample sizes. Future goals should include determining the reasons for the failure of the MIA in detecting DENV NS1, selecting a panel of appropriate markers to differentiate non-severe from severe cases of DENV prior to progression, and optimizing the inclusion of these markers to an appropriate number.
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胡夕春 and Xichun Hu. "Study on the use of potential prognostic parameters in breast cancer patients." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2001. http://hub.hku.hk/bib/B30158138.
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Alessandria, Maria <1979>. "Sleep motor activity in parkinsonian syndromes at onset: a prospective study to determine potential diagnostic and prognostic markers." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2014. http://amsdottorato.unibo.it/6657/1/ALESSANDRIA_TESI.pdf.
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Aim of this study is to describe the possible diagnostic value of sleep disturbances in the differential diagnosis of neurodegenerative diseases characterized by parkinsonism at onset. 42 consecutive patients with parkinsonian features and disease duration up to 3 years were included in the BO-ProPark study. Each patient was evaluated twice, at baseline (T0) and 16 months later (T1). Patients were diagnosed as Parkinson disease (PD, 27 patients), PD plus (PD with cognitive impairment/dementia or dysautonomia, 4 patients) and parkinsonian syndrome (PS, 11 patients). All patients underwent a full night video-polysomnography scored by a neurologist blinded to the clinical diagnosis. Sleep efficiency and total sleep time were reduced in all patients; wake after sleep onset was higher in patients with atypical parkinsonisms than in PD patients. No significant differences between groups of patients were detected in other sleep parameters. The mean percentage of epochs with enhanced tonic muscle EMG activity during REM sleep was higher in PD plus and PS than in PD. No difference in phasic muscle EMG activity during REM sleep was seen between the two groups. REM behaviour disorder was more frequent in PD plus and PS than in PD patients. Our data suggest that REM sleep motor control is more frequently impaired at disease onset in patients with PS and PD plus compared to PD patients. The presence of RBD or an enhanced tonic muscle EMG activity in a patient with recent onset parkinsonian features should suggest a diagnosis of atypical parkinsonism, rather than PD. More data are needed to establish the diagnostic value of these features in the differential diagnosis of parkinsonisms. The evaluation of sleep disorders may be a useful tool in the differential diagnosis of parkinsonism at onset.
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Alessandria, Maria <1979>. "Sleep motor activity in parkinsonian syndromes at onset: a prospective study to determine potential diagnostic and prognostic markers." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2014. http://amsdottorato.unibo.it/6657/.
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Aim of this study is to describe the possible diagnostic value of sleep disturbances in the differential diagnosis of neurodegenerative diseases characterized by parkinsonism at onset. 42 consecutive patients with parkinsonian features and disease duration up to 3 years were included in the BO-ProPark study. Each patient was evaluated twice, at baseline (T0) and 16 months later (T1). Patients were diagnosed as Parkinson disease (PD, 27 patients), PD plus (PD with cognitive impairment/dementia or dysautonomia, 4 patients) and parkinsonian syndrome (PS, 11 patients). All patients underwent a full night video-polysomnography scored by a neurologist blinded to the clinical diagnosis. Sleep efficiency and total sleep time were reduced in all patients; wake after sleep onset was higher in patients with atypical parkinsonisms than in PD patients. No significant differences between groups of patients were detected in other sleep parameters. The mean percentage of epochs with enhanced tonic muscle EMG activity during REM sleep was higher in PD plus and PS than in PD. No difference in phasic muscle EMG activity during REM sleep was seen between the two groups. REM behaviour disorder was more frequent in PD plus and PS than in PD patients. Our data suggest that REM sleep motor control is more frequently impaired at disease onset in patients with PS and PD plus compared to PD patients. The presence of RBD or an enhanced tonic muscle EMG activity in a patient with recent onset parkinsonian features should suggest a diagnosis of atypical parkinsonism, rather than PD. More data are needed to establish the diagnostic value of these features in the differential diagnosis of parkinsonisms. The evaluation of sleep disorders may be a useful tool in the differential diagnosis of parkinsonism at onset.
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Arrambide, García Georgina. "Study of diagnostic and prognostic clinical, biological, and magnetic resonance imaging markers at the time of a clinically isolated syndrome." Doctoral thesis, Universitat Autònoma de Barcelona, 2016. http://hdl.handle.net/10803/384610.
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En este trabajo estudiamos marcadores con valor diagnóstico o pronóstico en el momento de presentar un síndrome clínico aislado (CIS, del inglés clinically isolated syndrome). Dado que presentar un CIS representa un riesgo para desarrollar esclerosis múltiple (EM), se considera crucial identificar qué pacientes tendrán un segundo brote y determinar el grado de acumulación de discapacidad a medio y largo plazo. Por ello, aún se considera necesario identificar marcadores que representen los diferentes aspectos de esta enfermedad, especialmente si se demuestra su utilidad en la práctica clínica diaria. Así, nuestro objetivo fue determinar el valor diagnóstico y pronóstico de marcadores clínicos, biológicos y radiológicos en el momento del CIS.
Primero, dado que el espectro de enfermedades de la neuromielitis óptica (NMOSD, del inglés neuromyelitis optica spectrum disorders) es uno de los principales diagnósticos diferenciales de la EM, decidimos evaluar la utilidad de determinar sistemáticamente la presencia de anticuerpos NMO-IgG en el momento del CIS, observando que tal abordaje no es necesario ya que la determinación de este anticuerpo fue negativa en la mayoría de los pacientes. Por tanto, otras características clínicas y radiológicas también deben considerarse durante el diagnóstico diferencial y esta determinación podría realizarse en casos indeterminados. Posteriormente se estableció una colaboración con Aurélie Ruet y Bruno Brochet [Centre Hospitalo-Universitaire (CHU) de Bordeaux, INSERM-CHU centre d’Investigation Clinique, Université de Bordeaux en Francia] para evaluar más a fondo el valor añadido de presentar dos o más factores predictivos de EM, previamente identificados por ellos, en pacientes con CIS que no cumplen los criterios diagnósticos de 2010 para diseminación en espacio, observando que si bien es más bajo, los pacientes con combinaciones de estos factores aún presentan un riesgo de desarrollar EM y deberían ser monitorizados más estrechamente. De igual forma, la utilidad de realizar una RM medular en el momento del CIS se considera un tema controvertido. Por tanto, analizamos su valor diagnóstico y pronóstico añadido, observando que aunque su aportación a los criterios diagnósticos es más bien modesta, la presencia de lesiones medulares representa un riesgo aumentado para evolucionar a una EM y para desarrollar una mayor discapacidad. También establecimos otra colaboración con la compañía israelí Glycominds, Inc., para validar el valor predictivo del gMS-Classifier2, un algoritmo que incorpora anticuerpos anti-glicano IgM en suero, diseñado con el objetivo de identificar pacientes con CIS en riesgo de presentar un segundo brote. El gMS-Classifier2 resultó ser un factor de riesgo independiente para EM, si bien los hallazgos en la RM representan un riesgo más elevado. Finalmente, valoramos varios marcadores biológicos en líquido cefalorraquídeo durante una fase de screening y una de validación que requirió trabajos colaborativos con Jens Kuhle, Ludwig Kappos (Department of Neurology, University Hospital Basel, en Suiza), Luisa María Villar y José Carlos Álvarez-Cermeño [Departamentos de Inmunología y Neurología del Hospital Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) en Madrid]. De todos los biomarcadores testados, los niveles basales de NfL resultaron ser factores independientes de riesgo para desarrollar una EM, siendo los hallazgos de RM nuevamente los mayores indicadores de riesgo. Además, los NfL presentaron fuertes correlaciones con los cambios en el volumen cerebral a los cinco años de seguimiento.The present work is concerned with finding diagnostic and prognostic markers at the time of a clinically isolated syndrome (CIS). Given that presenting a CIS indicates the possibility of developing multiple sclerosis (MS), it is considered crucial to identify which patients will present a second attack and to determine the degree of disability accumulation over the medium to long-term. Therefore, the search for markers that capture the different aspects of this disease is still considered necessary, particularly if they demonstrate to be useful in the daily clinical practice. Therefore, we aimed to determine the diagnostic and prognostic value of a number of clinical, biological, and radiological markers available at the time of the CIS. First, considering neuromyelitis optica spectrum disorders (NMOSD) as one of the main differential diagnoses of MS after a first attack, we decided to assess the value of systematically determining NMO-IgG status at the time of a CIS, observing that such approach is not necessary since the antibody determination was negative in most patients. Therefore, other clinical and radiological characteristics should also be taken into account during the differential diagnosis and this test could be considered in indeterminate cases. Next, a collaborative work was established with Drs. Aurélie Ruet and Bruno Brochet [Centre Hospitalo-Universitaire (CHU) de Bordeaux, INSERM-CHU centre d’Investigation Clinique, Université de Bordeaux, France] to further assess the added value of presenting ≥2 predictive factors for MS, previously identified by them, in patients not fulfilling the 2010 criteria for dissemination in space, and observed that although lower, patients with combinations of these predictive factors are still at risk of developing MS and should be monitored closely. Likewise, the usefulness of a baseline spinal cord MRI at the time of a CIS is still somewhat controversial. Therefore, we analysed its added diagnostic and prognostic value, observing that although the diagnostic value is modest, presence of spinal cord lesions do pose an increased and independent risk for both evolution to MS and disability accumulation. One more collaboration was established with the Israeli company Glycominds, Inc., to validate the predictive value of gMS-Classifier2, an algorithm incorporating serum IgM anti-glycan antibodies, designed with the aim of identifying CIS patients at risk of a second demyelinating attack. gMS-Classifier2 turned out to be an independent risk factor for clinically definite MS, although MRI findings still posed a higher risk. Finally, we evaluated a number of biological markers in cerebrospinal fluid during a screening and a validation phase that involved a couple of collaborative works with Jens Kuhle, Ludwig Kappos (Department of Neurology, University Hospital Basel, in Switzerland), Luisa María Villar, and José Carlos Álvarez-Cermeño (Departments of Neurology and Immunology, Multiple Sclerosis Unit, Hospital Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) in Madrid). Of all biomarkers, only baseline neurofilament light chain levels were independent risk factors for MS with MRI findings again posing the highest risk but, interestingly, they showed very strong correlations with brain volume changes at five years of follow-up.
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Jeffery, Penelope Lorrelle. "An Investigation into the role of the ghrelin axis in hormone-dependent cancer and characterisation of a novel Exon 3-deleted preproghrelin isoform and its murine homologue." Thesis, Queensland University of Technology, 2005. https://eprints.qut.edu.au/16260/1/Penelope_Jeffrey_Thesis.pdf.
Full textAbstract:
Ghrelin is a 28 amino acid peptide hormone with a unique octanoic acid modification that has an extensive range of physiological effects, including stimulation of growth hormone (GH) release, appetite regulation, and modulation of reproductive functions. The cognate receptor for ghrelin is the growth hormone secretagogue receptor (GHS-R), a G protein-coupled receptor with two documented isoforms, the functional GHS-R type 1a and the C-terminally truncated GHS-R type 1b. Several ghrelin variants have also been identified in addition to the n-octanoylated form of ghrelin. In our laboratory, we have identified a novel exon 3-deleted preproghrelin variant that retains sequence for the mature ghrelin hormone and also encodes a novel C-terminal peptide (designated as C-terminal 3 peptide). There is emerging evidence to suggest that the ghrelin axis, encompassing ghrelin, several ghrelin variants and both forms of the GHS-R, is implicated in tumour growth. The objective of this project is to investigate the role of the ghrelin axis in hormone-dependent cancer and to further characterise the expression and function of the novel exon 3-deleted preproghrelin isoform.
Hormone-dependent cancers, including prostate and breast cancers, are significant causes of morbidity and mortality in the Western world. Improved diagnoses and treatments earlier in the progression of the disease are urgently required to improve patient outcomes. Growth factors play an integral role in prostate and breast cancer, particularly in the emergence of aggressive, hormone-refractory disease that is resistant to standard therapies. We have previously identified ghrelin as being a novel growth factor for prostate cancer cells in vitro and have hypothesised that this may be extended to other hormone-dependent cancer types including breast cancer.
In the current study, techniques including real-time quantitative RT-PCR, Western blot analysis and immunohistochemistry have been used to determine and quantitate ghrelin, exon 3-deleted preproghrelin and GHS-R expression in prostate and breast cancer. Ghrelin and exon 3-deleted preproghrelin are highly expressed in prostate cancer tissues compared to expression levels in normal prostate glands. Similarly, breast carcinoma specimens display greater immunoreactivity for ghrelin and exon 3-deleted preproghrelin than normal breast tissues. Expression of the exon 3-deleted preproghrelin mRNA isoform is upregulated in the oestrogen-independent, highly malignant MDA-MB-435 breast cancer cell line compared to the non-tumourigenic MCF-10A breast epithelial cell line, suggesting that augmented transcription of the isoform is associated with an increased malignant potential in breast cancer. The functional GHS-R type 1a is expressed in normal breast tissue and breast cancer specimens and cell lines. In contrast, the truncated GHS-R type 1b isoform is exclusively expressed in breast carcinoma. These data suggest that GHS-R type 1b, ghrelin and exon 3-deleted preproghrelin display potential as novel diagnostic markers for prostate and breast cancer.
These studies have been the first to demonstrate that ghrelin may have an important role in cell proliferation in breast and prostate cancer. Functional assays demonstrated that (10nM) ghrelin stimulated proliferation in the LNCaP prostate cancer cell lines (45.0 ± 1.7% above control, P <0.01) and rapidly activated the ERK 1/2 mitogen-activated kinase (MAPK) pathway in both PC3 and LNCaP cell lines. It does not, however, protect these cells from chemically-induced apoptosis. The MAPK inhibitors PD98059 and U0126 blocked ghrelin-induced MAPK activation, as well as cell proliferation, in both cell lines. Prostate cancer cells secrete mature ghrelin in vitro, and may therefore stimulate MAPK pathways in an autocrine manner. Ghrelin also appears to act as a growth factor in breast cancer cell proliferation, as the growth of MDA-MB-435 and MDA-MB-231 breast cancer cell lines is significantly increased by ghrelin treatment. Our findings suggest that the ghrelin axis could provide an important new target for adjunctive therapies for both breast and prostate cancer.
The C-terminal 3 peptide derived from exon 3-deleted preproghrelin may be an important new component of the ghrelin axis and studies into its function are currently in progress. Although it did not induce MAPK cascades or stimulate proliferation in prostate or breast cancer cell lines, the discovery of a murine counterpart, exon 4-deleted preproghrelin, indicates that it is highly conserved. Exon 4-deleted preproghrelin is expressed in all mouse tissues examined, with stomach being the predominant site of synthesis. Other components of the ghrelin axis were also found to be present in a wide-range of mouse tissues including brain, ovary and prostate. This comprehensive report has paved the way for future work with in vivo mouse models of cancer.
This study has provided a substantial basis for the further evaluation of ghrelin, exon 3-deleted preproghrelin and the GHS-R type 1b as novel diagnostic/prognostic markers for prostate and breast cancer and supports the rationale for targeting the ghrelin axis for treatment of these tumours.
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Riley, Richard David. "Evidence synthesis of prognostic marker studies." Thesis, University of Leicester, 2004. http://hdl.handle.net/2381/30480.
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Havervall, Carolina. "CXCL13: A Prognostic Marker in Multiple Sclerosis." Thesis, Södertörn University College, School of Life Sciences, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:sh:diva-3656.
Full textAbstract:
In the demyelinating autoimmune disease multiple sclerosis (MS) there is a great need for validated prognostic biomarkers that can give information about both prognosis and disease course. So far only clinical parameters have been shown to predict future outcome. CXCL13 is a potent B cell chemoattractant that has been suggested to be a potential biomarker candidate. The aim of this study was to investigate the usefulness of CXCL13 as a prognostic biomarker for MS.
Clinical, paraclinical, laboratory and MRI data about a large group of MS patients and controls were collected. CXCL13 levels in cerebrospinal fluid (CSF) samples from these patients were determined by standard enzymelinked immunosorbent assay (ELISA).
In general CXCL13 were increased in CSF in MS, especially in relapsing-remitting MS during relapses, i.e. with ongoing inflammations in the central nervous system. CXCL13 is a good candidate prognostic marker for MS, since newly diagnosed MS with high CXCL13 levels showed worsened disease course within five years. Most importantly, MS conversion occurred in higher rate in possible MS patients with high concentrations of CXCL13 in CSF, and in a shorter time point. This observation may support an early treatment decision in these patients.
In conclusion, this study provides support for an association between CXCL13 levels in the CSF and later development of disease severity in MS.
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Thakkar, Dipti S. "Telomerase : a prognostic marker and therapeutic target." Thesis, University of Central Lancashire, 2010. http://clok.uclan.ac.uk/1872/.
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Malignant glioma is the most common and aggressive form of tumours and is usually refractory to therapy. Telomerase and its altered activity, distinguishing cancer cells, is an attractive molecular target in glioma therapeutics. The aim of this thesis was to silence telomerase at the genetic level with a view to highlight the changes caused in the cancer proteome and identify the potential downstream pathways controlled by telomerase in tumour progression and maintenance. A comprehensive proteomic study utilizing 2D-DIGE and MALDI-TOF were used to assess the effect of inhibiting two different regulatory mechanisms of telomerase in glioma. RNAi was used to target hTERT and Hsp90α. Inhibition of telomerase activity resulted in down regulation of various cytoskeletal proteins with correlative evidence of the involvement of telomerase in regulating the expression of vimentin. Vimentin plays an important role in tumour metastasis and is used as an indicator of glioma metastasis. Inhibition of telomerase via sihTERT results in the down regulation of vimentin expression in glioma cell lines in a grade specific manner. While, 9 of 12 glioblastoma tissues (grade IV) showed vimentin to be highly expressed, its expression was absent in lower grades and normal tissues. This suggests that vimentin can be potentially used as a glioma progressive marker. This is the first study to report the potential involvement of telomerase in the regulation of vimentin expression. This study also identified that combination therapy, comprising siRNA targeted towards telomerase regulatory mechanisms and the natural product Epigallocatechin-3-gallate (ECGC), results in decreased cell viability producing comparable results to that of other chemotherapeutic drugs.
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Zhang, Yi 1956. "Intermediate filaments : the prognostic marker for conjunctival melanomas." Thesis, McGill University, 2000. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=33456.
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Intermediate filaments (IFs) are highly regulated and conserved during cell transformation and tumor development. The co-expression of keratin 8, 18 and vimentin has been shown to be related to recurrence and metastasis in both cutaneous and uveal melanomas. This thesis provides the first immunohistochemical evidence that the co-expression of keratin 8, 18 and vimentin is present in one third of conjunctival melanomas. The results show that conjunctival melanomas co-expressing IFs are mixed cell tumors with diffuse growth patterns. It is also shown that melanoma cells co-expressing IFs are mainly located around the peripheral or marginal area of the tumors. In addition, this thesis indicates that the initial tumor thickness significantly increases in conjunctival melanomas co-expressing IFs. Therefore, it is demonstrated that the co-expression of IFs plays an important role in influencing the malignant progression of conjunctival melanomas, and the co-expression of IFs can be used as a prognostic marker for conjunctival melanomas.
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Bennett, Dr Alexander. ""Diagnostic and Prognostic Imaging in Spondyloarthropathy"." Thesis, University of Leeds, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.534424.
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Kon, Samantha Swee Chin. "Habitual gait speed : a novel prognostic marker in COPD?" Thesis, Imperial College London, 2015. http://hdl.handle.net/10044/1/56925.
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Forced expiatory volume in one second (FEV1) is the most widely accepted marker in COPD. However, COPD is now well recognised as a multisystem and heterogeneous disease, and it is unlikely that a single marker could reflect the complex range of observed pathophysiologic changes. Exercise intolerance is a common symptom in COPD, and reflects both lung and skeletal muscle dysfunction. Logistical issues often mean physical performance is not routinely measured objectively in all clinical settings. Gait speed is an easy, quick to perform established measure of physical performance in the elderly, and has been recommended as a “vital sign” or “global marker of well-being” that reflects biological rather than chronological age. Functional decline is common to both ageing and COPD but gait speed has not been validated in COPD. In 586 patients with stable COPD, usual gait speed over 4 metres (4MGS) had excellent reliability and showed concurrent validity with well-established measures in COPD. Stratification according to slow 4MGS identified significant impairments in exercise capacity and poor health-related quality of life. Subsequent studies showed that 4MGS was responsive to intervention with pulmonary rehabilitation (n=301) and longitudinal decline at one year (n=162). Using both distribution- and anchor-based approaches the minimum clinically important difference was estimated to be 0.11ms-1. In a cohort of patients with stable COPD (n=402), slower 4MGS was associated with significantly increased risk of all-cause mortality at three years, and provided prognostic information independent of FEV1. In a prospective cohort of 213 patients admitted to hospital with an acute exacerbation of COPD, slower 4MGS was associated with significantly increased odds of all-cause readmission at 90 days. The 4MGS is a reliable measure of physical performance that has potential utility as a simple assessment tool to provide a more comprehensive assessment of patients with COPD.
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Whiteley, William Nichol. "Blood markers for the diagnosis and prognosis of stroke." Thesis, University of Edinburgh, 2011. http://hdl.handle.net/1842/5609.
Full textAbstract:
Many blood markers have been associated with stroke. I set out to determine whether blood markers can be applied to: (i) improve the accuracy of the clinical diagnosis of stroke or TIA, and/or (ii) improve the prediction of poor outcome in patients who are still symptomatic at the time of admission with stroke or TIA. I systematically reviewed the existing literature on the diagnostic performance of a range of blood markers measured soon after stroke onset, to inform the choice of markers for my subsequent prospective studies in this thesis. Many studies had deficiencies in their design, which may have explained the apparently – and perhaps spuriously - impressive diagnostic performance of several markers. In the light of these data I was able to improve the design of my own studies and suggest how future studies of diagnostic markers could be improved. In order to define an appropriate comparator test for assessing the diagnostic accuracy of blood markers, I first examined the performance of emergency room nurses and doctors. I assessed the accuracy of their diagnosis of TIA or stroke (‘acute cerebrovascular disease’) in patients presenting with symptoms of suspected stroke, and compared them with a number of stroke diagnostic scales. In the 405 patients recruited to the study, the sensitivity of emergency department staff was 77% and specificity 58%. Each stroke diagnostic scale had a slightly better sensitivity, though worse specificity, than an emergency department clinician. I decided to use the diagnosis by an emergency department clinician of ‘probable or definite acute cerebrovascular disease’ as the best clinical performance reference standard. In blood taken from the same cohort of 405 patients, accredited research laboratories measured markers of inflammation, thrombosis, thrombolysis, cardiac strain and cerebral damage. Tissue plasminogen activator and loge N-terminal pro brain natriuretic peptide were associated positively with a diagnosis of acute cerebrovascular disease, though each marker did not add diagnostic value to the diagnosis of an emergency department doctor or nurse. I systematically reviewed the literature examining the association between the levels of blood markers with poor outcome (i.e. death or dependency) after stroke. I found that although almost all markers studied had a positive association with poor outcome, there were methodological problems with many studies, chiefly small sample size, publication bias or within study reporting biases, and lack of adjustment for important confounders such as age or stroke severity. With data from the Edinburgh Stroke Study, I examined the association between circulating markers of the inflammatory response (white cell count, interleukin-6, Creactive protein and fibrinogen) and poor outcome after stroke. After adjustment for age, whether the patient lived alone, was independent of activities of daily living, was orientated, able to lift both arms and able to walk, I found that higher levels of interleukin-6, white cell count and glucose were associated with poor outcome. The relevant test of a biological marker is not its predictive ability alone, but whether, when added to a validated predictive model based on clinical variables, it improves the prediction of outcome. No individual marker improved the prediction of poor outcome when added to a validated prognostic model based on clinical variables alone. From my cohort of 405 patients with suspected stroke 285 patients had a confirmed diagnosis. Follow up of these 285 patients with confirmed acute cerebrovascular disease showed that, after adjustment for neurological impairment and age, only interleukin-6 and N-terminal pro brain natriuretic peptide were significantly associated with death or disability at 3 months. Neither marker improved the predictions of a model to predict poor outcome based on clinical variables alone. To examine the relationship between circulating markers of the inflammatory response and recurrent stroke, myocardial infarction, and vascular death (‘recurrent vascular events’), again I used data from the Edinburgh Stroke Study. After adjustment for clinical predictors (age, prior MI, stroke, or TIA and AF) I found that higher levels of interleukin-6, C-reactive protein and fibrinogen remained significantly associated with an increased risk of recurrent vascular events. However, the relationship with deaths from all causes was somewhat stronger for each marker, perhaps suggesting that higher marker levels were associated with debility rather than vascular events per se. In conclusion, I found no marker measured could improve on the diagnostic accuracy of an emergency department clinician for acute cerebrovascular disease, nor improve the prediction of poor outcome by a prognostic model based upon clinical variables. The work of this thesis does not support the routine use of blood markers as an aid to the diagnosis of, or the prediction of outcome of, acute stroke.
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Karčiauskaitė, Dovilė. "Biocheminių miokardo pažeidimo žymenų diagnostinė ir prognostinė vertė." Doctoral thesis, Lithuanian Academic Libraries Network (LABT), 2005. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2005~D_20050907_090908-71878.
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In the present study clinical performance of new highly cardiospecific biochemical markers of myocardial injury was investigated and these markers were compared with conventional enzymes. The multimarker risk assessment score index, including biochemical markers of myocardial injury, inflammation and haemostasis, was developed for the prognosis of patients after ACS. The prognostic value of BNP concentration changes in predicting LV remodeling and dysfunction after MI was evaluated along with other biochemical markers of myocardial injury.
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Borssén, Magnus. "DNA methylation as a prognostic marker i acute lymphoblastic leukemia." Doctoral thesis, Umeå universitet, Patologi, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-127225.
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Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Most ALL cases originate from immature B-cells (BCP-ALL) and are characterized by reoccurring structural genetic aberrations. These aberrations hold information of the pathogenesis of ALL and are used for risk stratification in treatment. Despite increased knowledge of genetic aberrations in pediatric T-cell ALL (T-ALL), no reliable molecular genetic markers exist for identifying patients with higher risk of relapse. The lack of molecular prognostic markers is also evident in patients with relapsed ALL. During the last decades, aberrant epigenetic mechanisms including DNA methylation have emerged as important components in cancer development. Telomere maintenance is another important factor in malignant transformation and is crucial for long-term cell survival. Like DNA methylation, telomere length maintenance has also been implicated to reflect outcomes for patients with leukemia. In this thesis, the prognostic relevance of DNA methylation and telomere length was investigated in pediatric ALL at diagnosis and relapse. The telomere length (TL) was significantly shorter in diagnostic ALL samples compared to normal bone marrow samples collected at cessation of therapy, reflecting the proliferation associated telomere length shortening. Prognostic relevance of TL was shown in low-risk BCP-ALL patients where longer telomeres at diagnosis were associated with higher risk of relapse. Genome-wide methylation characterization by arrays in diagnostic T-ALL samples identified two distinct methylation subgroups denoted CIMP+ (CpG Island Methylator Phenotype high) and CIMP- (low). CIMP- T-ALL patients had significantly worse outcome compared to CIMP+ cases. These results were confirmed in a Nordic cohort treated according to the current NOPHO-ALL2008 protocol. By combining minimal residual disease (MRD) status at treatment day 29 and CIMP status at diagnosis we could further separate T-ALL patients into risk groups. Likewise, the CIMP profile could separate relapsed BCP-ALL patients into risk groups, where the CIMP- cases had a significantly worse outcome compared to CIMP+ cases. From these data we conclude that DNA methylation subgrouping is a promising prognostic marker in T-ALL, as well as in relapsed BCP-ALL two groups where reliable prognostic markers are currently missing. By elucidating the biology behind the different CIMP profiles, the pathogenesis of ALL will be further understood and may contribute to new treatment strategies.
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Leo, Elisa <1981>. "Marker molecolari relativi all'infezione da Papillomavirus umani: significato diagnostico e prognostico in lesioni virus-correlate." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2010. http://amsdottorato.unibo.it/2297/1/leo_elisa_tesi.pdf.
Full textAbstract:
Introduzione: Il cervico-carcinoma è la seconda neoplasia maligna per incidenza e mortalità nelle donne in tutto il mondo dopo il cancro al seno. L’infezione persistente da Papillomavirus Umani (HPV) è causa necessaria dell’insorgenza del cervico-carcinoma e delle sue lesioni pre-cancerose.
L’infezione da HPV si associa anche ad altri carcinomi del distretto ano-genitale (a livello anale, vulvare, vaginale e del pene) e a circa il 25% dei carcinomi squamosi dell’orofaringe. I circa 40 genotipi di HPV che infettano la mucosa genitale vengono suddivisi in alto rischio (HR-HPV) e basso rischio (LR-HPV) oncogeno a seconda della alta e bassa associazione con la neoplasia cervicale. I 13 genotipi a più alto rischio oncogeno sono 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 e 68. Di questi, otto (16, 18, 31, 33, 35, 45, 52 e 58) sono associati alla maggior parte dei carcinomi cervicali (circa 89%) e i genotipi 16 e 18 da soli sono riscontrati nel 70% circa delle neoplasie. L’insorgenza e progressione delle lesioni preneoplastiche cervicali è, però, associata non solo alla presenza di HPV ad alto rischio, ma, soprattutto, alla persistenza virale (> 18 mesi), alla capacità di integrazione degli HPV ad alto rischio e alla conseguente sovraespressione delle oncoproteine E6/E7. Inoltre, l’integrazione è spesso favorita da un’alta carica virale soprattutto per quanto riguarda alcuni genotipi (HPV16 e 18).
L’infezione da HPV non interessa solo la cervice uterina ma tutto il distretto ano-genitale e quello testa-collo. L’HPV, in particolare il genotipo 16, è implicato, infatti, nell’insorgenza delle lesioni preneoplastiche della vulva (VIN) classificate come VIN classiche e nei carcinomi ad esse associati. L’incidenza del carcinoma vulvare in Europa è di 1.5/100.000 di cui circa il 45% è dovuto a HR-HPV (80% ad HPV16). Nonostante l’associazione tra HPV16 e carcinoma vulvare sia alta, ancora poco si conosce sul ruolo della carica virale e dell’integrazione in tali lesioni.
Le lesioni che possono presentarsi nella regione testa-collo possono essere sia di natura benigna che maligna. I genotipi più frequentemente riscontrati in associazione a lesioni benigne (papillomi) sono HPV 6 e 11, quelli associati a forme tumorali (HNSCC) sono il genotipo 18 ma soprattutto il 16.
Molti aspetti del coinvolgimento di HPV in queste patologie non sono ancora perfettamente conosciuti e spesso studi su tale argomento hanno mostrato risultati contraddittori, soprattutto perché vengono utilizzate metodiche con gradi diversi di sensibilità e specificità.
Recenti dati di letteratura hanno tuttavia messo in evidenza che i pazienti affetti da HNSCC positivi ad HPV hanno una elevata risposta al trattamento chemioradioterapico rispetto ai pazienti HPV-negativi con un notevole impatto sul controllo locale e sulla sopravvivenza ma soprattutto sulla qualità di vita di tali pazienti, evitando di sottoporli a chirurgia sicuramente demolitiva.
Scopo del lavoro: Sulla base di queste premesse, scopo di questo lavoro è stato quello di valutare l’importanza di marker quali la presenza/persistenza di HPV, la carica virale, la valutazione dello stato fisico del genoma virale e l’espressione degli mRNA oncogeni nella gestione di pazienti con lesioni preneoplastiche e neoplastiche di diverso grado, associate a papillomavirus mucosi.
Per la valutazione dei markers virologici di progressione neoplastica abbiamo sviluppato dei saggi di real time PCR qualitativi e quantitativi studiati in modo da poter fornire, contemporaneamente e a seconda delle esigenze, risposte specifiche non solo sulla presenza e persistenza dei diversi genotipi di HPV, ma anche sul rischio di insorgenza, progressione e recidiva delle lesioni mediante lo studio di markers virologici quali carica virale, integrazione ed espressione degli mRNA.
Abbiamo pertanto indirizzato la nostra attenzione verso tre popolazioni specifiche di pazienti:
- donne con lesioni vulvari preneoplastiche (VIN) e neoplastiche, allo scopo di comprendere i complessi meccanismi patogenetici di tali patologie non sempre associate ad infezione da HPV;
- pazienti con lesioni maligne a livello della regione testa-collo allo scopo di fornire informazioni utili all’elaborazione di un percorso terapeutico mirato (radiochemioterapico o chirurgico) a seconda o meno della presenza di infezione virale;
- donne con lesioni cervicali di alto grado, trattate chirurgicamente per la rimozione delle lesioni e seguite nel follow-up, per stabilire l’importanza di tali marker nella valutazione della persistenza virale al fine di prevenire recidive di malattia.
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Leo, Elisa <1981>. "Marker molecolari relativi all'infezione da Papillomavirus umani: significato diagnostico e prognostico in lesioni virus-correlate." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2010. http://amsdottorato.unibo.it/2297/.
Full textAbstract:
Introduzione: Il cervico-carcinoma è la seconda neoplasia maligna per incidenza e mortalità nelle donne in tutto il mondo dopo il cancro al seno. L’infezione persistente da Papillomavirus Umani (HPV) è causa necessaria dell’insorgenza del cervico-carcinoma e delle sue lesioni pre-cancerose.
L’infezione da HPV si associa anche ad altri carcinomi del distretto ano-genitale (a livello anale, vulvare, vaginale e del pene) e a circa il 25% dei carcinomi squamosi dell’orofaringe. I circa 40 genotipi di HPV che infettano la mucosa genitale vengono suddivisi in alto rischio (HR-HPV) e basso rischio (LR-HPV) oncogeno a seconda della alta e bassa associazione con la neoplasia cervicale. I 13 genotipi a più alto rischio oncogeno sono 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 e 68. Di questi, otto (16, 18, 31, 33, 35, 45, 52 e 58) sono associati alla maggior parte dei carcinomi cervicali (circa 89%) e i genotipi 16 e 18 da soli sono riscontrati nel 70% circa delle neoplasie. L’insorgenza e progressione delle lesioni preneoplastiche cervicali è, però, associata non solo alla presenza di HPV ad alto rischio, ma, soprattutto, alla persistenza virale (> 18 mesi), alla capacità di integrazione degli HPV ad alto rischio e alla conseguente sovraespressione delle oncoproteine E6/E7. Inoltre, l’integrazione è spesso favorita da un’alta carica virale soprattutto per quanto riguarda alcuni genotipi (HPV16 e 18).
L’infezione da HPV non interessa solo la cervice uterina ma tutto il distretto ano-genitale e quello testa-collo. L’HPV, in particolare il genotipo 16, è implicato, infatti, nell’insorgenza delle lesioni preneoplastiche della vulva (VIN) classificate come VIN classiche e nei carcinomi ad esse associati. L’incidenza del carcinoma vulvare in Europa è di 1.5/100.000 di cui circa il 45% è dovuto a HR-HPV (80% ad HPV16). Nonostante l’associazione tra HPV16 e carcinoma vulvare sia alta, ancora poco si conosce sul ruolo della carica virale e dell’integrazione in tali lesioni.
Le lesioni che possono presentarsi nella regione testa-collo possono essere sia di natura benigna che maligna. I genotipi più frequentemente riscontrati in associazione a lesioni benigne (papillomi) sono HPV 6 e 11, quelli associati a forme tumorali (HNSCC) sono il genotipo 18 ma soprattutto il 16.
Molti aspetti del coinvolgimento di HPV in queste patologie non sono ancora perfettamente conosciuti e spesso studi su tale argomento hanno mostrato risultati contraddittori, soprattutto perché vengono utilizzate metodiche con gradi diversi di sensibilità e specificità.
Recenti dati di letteratura hanno tuttavia messo in evidenza che i pazienti affetti da HNSCC positivi ad HPV hanno una elevata risposta al trattamento chemioradioterapico rispetto ai pazienti HPV-negativi con un notevole impatto sul controllo locale e sulla sopravvivenza ma soprattutto sulla qualità di vita di tali pazienti, evitando di sottoporli a chirurgia sicuramente demolitiva.
Scopo del lavoro: Sulla base di queste premesse, scopo di questo lavoro è stato quello di valutare l’importanza di marker quali la presenza/persistenza di HPV, la carica virale, la valutazione dello stato fisico del genoma virale e l’espressione degli mRNA oncogeni nella gestione di pazienti con lesioni preneoplastiche e neoplastiche di diverso grado, associate a papillomavirus mucosi.
Per la valutazione dei markers virologici di progressione neoplastica abbiamo sviluppato dei saggi di real time PCR qualitativi e quantitativi studiati in modo da poter fornire, contemporaneamente e a seconda delle esigenze, risposte specifiche non solo sulla presenza e persistenza dei diversi genotipi di HPV, ma anche sul rischio di insorgenza, progressione e recidiva delle lesioni mediante lo studio di markers virologici quali carica virale, integrazione ed espressione degli mRNA.
Abbiamo pertanto indirizzato la nostra attenzione verso tre popolazioni specifiche di pazienti:
- donne con lesioni vulvari preneoplastiche (VIN) e neoplastiche, allo scopo di comprendere i complessi meccanismi patogenetici di tali patologie non sempre associate ad infezione da HPV;
- pazienti con lesioni maligne a livello della regione testa-collo allo scopo di fornire informazioni utili all’elaborazione di un percorso terapeutico mirato (radiochemioterapico o chirurgico) a seconda o meno della presenza di infezione virale;
- donne con lesioni cervicali di alto grado, trattate chirurgicamente per la rimozione delle lesioni e seguite nel follow-up, per stabilire l’importanza di tali marker nella valutazione della persistenza virale al fine di prevenire recidive di malattia.
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Li, Sin Wan. "Development of immunoassays for prognosis and diagnosis of cardiovascular diseases /." View abstract or full-text, 2007. http://library.ust.hk/cgi/db/thesis.pl?CHEM%202007%20LI.
Full text
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Nieto, Mark E. "Naval aviation aging wiring : prognostic and diagnostic solutions /." Thesis, Monterey, Calif. : Springfield, Va. : Naval Postgraduate School ; Available from National Technical Information Service, 2000. http://handle.dtic.mil/100.2/ADA387353.
Full textAbstract:
Thesis (M.S. in Management) Naval Postgraduate School, Dec. 2000.Thesis advisor(s): Eaton, Donald ; Kang, Keebom. "December 2000." Includes bibliographical references (p. 61-63). Also available online.
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Tsim, Selina. "Diagnostic and prognostic biomarkers of malignant pleural mesothelioma." Thesis, University of Glasgow, 2018. http://theses.gla.ac.uk/30687/.
Full textAbstract:
Malignant Pleural Mesothelioma (MPM) is an aggressive intrathoracic malignancy with an overall poor prognosis. MPM is associated with asbestos exposure but has a long latency period between exposure and disease development. Incidence of MPM in the UK is therefore still rising, predicted to reach a peak in 2020. The majority of patients with MPM present with breathlessness, frequently due to a pleural effusion and/or chest pain. Diagnosis of MPM can be difficult. Radiological detection of early stage MPM in particular can be challenging, as pleural tumour, nodularity or significant pleural thickening may not be evident. Diagnosis is further complicated by the low yield of pleural fluid cytology examination in MPM and pleural biopsy is therefore usually required to allow definitive diagnosis. This can be achieved under image guidance, at surgical thoracoscopy or at local anaesthetic thoracoscopy (LAT). A significant number of patients are either elderly or have co-morbidity precluding general anaesthesia and surgical thoracoscopy. Image-guided pleural biopsy is not always feasible, particularly in the absence of significant pleural thickening. LAT remains a limited resource in the UK. A non-invasive biomarker of MPM, which could be performed early in the patient’s presentation, and that could be available to most hospitals, would therefore be a major clinical advance, allowing clinicians to direct appropriate patients to specialist centres with access to LAT and specialist MDT input where MPM appears likely. There have been several potential blood biomarkers identified in the mesothelioma literature, including the most widely studied, Mesothelin, and more recently Fibulin-3 and SOMAscanTM. Unfortunately study results have been variably limited by retrospective study design, inconsistent sampling time points, inconsistent results and lack of external validation, therefore despite initial promising results, none of these biomarkers have entered routine clinical practice for diagnosis. Similarly, utility of imaging biomarkers such as perfusion Computed Tomography (CT), Positron Emission Tomography (PET) and Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) has been limited by high radiation dose, limited availability, and requirement for bulky (and therefore late stage) disease for assessment respectively. In chapter 2, study design, recruitment and preliminary results of the DIAPHRAGM (Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma) study are reported. A prospective, multi-centre study was designed, recruiting patients with suspected pleural malignancy (SPM) at initial presentation to secondary care services, from a mixture of academic and more clinical units in the UK and Ireland, in addition to asbestos-exposed control subjects. In one of the largest biomarker studies in mesothelioma to date, 639 patients with SPM and 113 asbestos-exposed control subjects were recruited over three years. Data cleaning is being finalised by the Cancer Research UK Clinical Trials Unit Glasgow at the time of writing. Preliminary results reveal that 26% (n=154) patients recruited to the SPM cohort were diagnosed with MPM, 33% (n=209) had secondary pleural malignancy and 34% (n=218) were diagnosed with benign pleural disease. A final diagnosis is awaited in 7% (n=47) at the time of writing. SOMAscanTM and Fibulin-3 biomarker analyses are ongoing and DIAPHRAGM will definitively answer the question of diagnostic utility of these blood biomarkers in routine clinical practice, in a ‘real-life’ MPM population, relative to that of Mesothelin. In chapter 3, contrast-enhanced MRI was performed in patients with suspected MPM and a novel MRI biomarker of pleural malignancy defined (Early Contrast Enhancement – ECE). ECE was defined as a peak in pleural signal intensity at or before 4.5 minutes after intravenous Gadobutrol administration. ECE assessment was successfully performed in all patients who underwent contrast-enhanced MRI. This included patients with pleural thickening < 10mm (49/58 (84%)), the mean pleural thickness of all patients was 5mm. ECE demonstrated good overall diagnostic performance for the detection of pleural malignancy (sensitivity 83% (95% CI 61 – 94), specificity 83% (95% CI 68 - 91%), positive predictive value 68% (95% CI 47 – 84%), negative predictive value 92% (95% CI 78 – 97%)), comparable to morphology assessment at CT morphology and MRI morphology by experienced thoracic radiologists. In addition, ECE demonstrated good reproducibility (inter-observer κ = 0.864), superior to subjective morphology assessment at CT and MRI. Mean signal intensity gradient (MSIG), a marker of patient’s contrast enhancement pattern, correlated with tumour Microvessel Density (MVD) using Factor VII immunostain (Spearman’s rho = 0.43, p=0.02). Additionally, a high MSIG (>0.533AU/s), indicative of high tumour vascularity, was associated with poor median overall survival (12 months vs. 20 months, p=0.047). Staging of MPM represents an additional challenge to clinicians. This is due to the complex morphology and often rind-like growth pattern of MPM. In addition, delineation of pleural disease from adjacent structures such as intercostal muscle and diaphragm can be difficult to assess, particularly at CT, which is the most commonly used imaging modality for diagnostic and staging assessment in MPM. Current clinical staging frequently underestimates extent of disease, with a significant proportion of patients being upstaged at time of surgery, and is limited by high inter-observer variability. Recent studies have reported the prognostic significance of CT-derived tumour volume; however, many of these studies have been limited by the laborious or complex nature of tumour segmentation, significant inter-observer variability or challenges encountered in separating pleural tumour from adjacent structures, which are often of similar density. MRI is superior to CT in the detection of invasion of the chest wall and diaphragm in MPM. In Chapter 4, MRI was used to quantitatively assess pleural tumour volume in 31 patients with MPM using novel semi-automated segmentation methodology. Four different segmentation methodologies, using Myrian® segmentation software were developed and examined. Optimum methodology was defined, based on the accuracy of volume estimates of an MRI phantom, visual-based analysis, intra-observer agreement and analysis time. Using the optimum methodology, there was acceptable error around the MRI phantom volume (3.6%), a reasonable analysis time (approximately 14 minutes), good intra-observer agreement (intra-class correlation coefficient (ICC) 0.875) and excellent inter-observer agreement (ICC 0.962). Patients with a high MRI-estimated tumour volume (≥300cm3) had a significantly poorer median overall survival (8.5 months vs. 20 months) and was a statistically significant prognostic variable on univariate (HR 2.273 (95% CI 1.162 – 4.446), p=0.016) and multi-variate Cox proportional hazards model (HR 2.114 (95% CI 1.046 – 4.270), p=0.037).
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MONTI, SARA. "Novel Diagnostic and Prognostic Approaches to Systemic Vasculitides." Doctoral thesis, Università degli studi di Pavia, 2021. http://hdl.handle.net/11571/1434015.
Full textAbstract:
Background. The management of giant cell arteritis (GCA) has gone through a number of paradigmatic changes in the last few years, including novel diagnostic approaches and treatment options.
Objectives. We aimed at investigating and improving the management of GCA by: (i) assessing the impact of the fast track ultrasonographic clinic (FTA) of the Rheumatology Department, IRCCS Policlinico S. Matteo, University of Pavia on the risk of permanent visual loss and future relapse; (ii) evaluating the role of quantitative ultrasound assessment in terms of diagnostic and prognostic outcomes in GCA in an International study in collaboration with the University of Oxford; (iii) contributing to the update of the European recommendations on the management of large vessel vasculitis (LVV) by leading on the systematic literature review and participating in the recommendations development process.
Methods. Patients referred for suspected GCA to the FTA were recruited if a diagnosis of GCA was confirmed. The role of quantitative ultrasound findings data was assessed, in collaboration with the University of Oxford, from the data of a large cohort study (TABUL Study) with the FTA cohort from the University of Pavia as an independent cohort. Quantitative ultrasound data [number of sites with halos, intima-media thickness (IMT), presence of bilateral halos] at the level of the temporal arteries (TA) and axillary arteries (AX) were assessed. Two systematic literature reviews (SLR) were performed by searching MEDLINE, EMBASE and Cochrane CENTRAL library to inform the European League Against Rheumatism (EULAR) update of the recommendations on the management of LVV.
Results. The GCA cohort included 160 patients [female 120 (75%), mean age 72.4±8.2 years]. Sixty-three (39.4%) evaluated with FTA, 97 (60.6%) with conventional approach. Since the introduction of FTA the need for TAB reduced by 93%. Median follow-up duration was shorter in the FTA group compared to the conventional one (0.9 vs. 5.0 years; p<0.001). Permanent visual loss (PVL) occurred in 8 (12.7%) FTA patients and 26 (26.8%) conventional ones (p=0.03). During COVID-19 there was a significant increase in the occurrence of PVL (40%) including bilateral blindness despite a regularly operating FTA clinic. Cumulative incidence of relapses and time to first relapse did not change after FTA introduction.
Quantitative ultrasound data were evaluated on 135 GCA patients from TABUL [female 92 (68%), age 73±8 years] and 72 patients from the independent cohort [female 33 (46%), age 75±7 years]. The best-fitting CDS model for TAB used maximum IMT and bilaterality of TA and AX halos. The best-fitting clinical model included raised inflammatory markers, polymyalgia rheumatica, headache and ischaemic symptoms. By combining CDS and clinical models a score to calculate the probability of having a positive TAB, given the ultrasonographic and clinical information, was derived. No significant association was found for prediction of clinical outcome at 6 months.
The SLRs confirmed the need to urgently refer the patient to a specialised team, including FTA clinics. The main treatment for LVV remain high-dose GC, however, more evidence has been retrieved to support the use of adjunctive immunosuppressants, including novel biologic treatments for GCA.
Conclusion. With our studies we have contributed to clarify the role of novel diagnostic approaches to the disease as part of fast track clinics and supported the role of ultrasound as a reliable diagnostic tool and to significantly reduce the risk of permanent blindness. A quantitative ultrasound analysis (extention and degree of vascular involvement) supported by clinical findings is useful to identify patients with a positive biopsy. Relapse rate and LV-complications did not change upon FTA introduction, highlighting the need for better disease activity monitoring and therapeutic strategies.Background. The management of giant cell arteritis (GCA) has gone through a number of paradigmatic changes in the last few years, including novel diagnostic approaches and treatment options. Objectives. We aimed at investigating and improving the management of GCA by: (i) assessing the impact of the fast track ultrasonographic clinic (FTA) of the Rheumatology Department, IRCCS Policlinico S. Matteo, University of Pavia on the risk of permanent visual loss and future relapse; (ii) evaluating the role of quantitative ultrasound assessment in terms of diagnostic and prognostic outcomes in GCA in an International study in collaboration with the University of Oxford; (iii) contributing to the update of the European recommendations on the management of large vessel vasculitis (LVV) by leading on the systematic literature review and participating in the recommendations development process. Methods. Patients referred for suspected GCA to the FTA were recruited if a diagnosis of GCA was confirmed. The role of quantitative ultrasound findings data was assessed, in collaboration with the University of Oxford, from the data of a large cohort study (TABUL Study) with the FTA cohort from the University of Pavia as an independent cohort. Quantitative ultrasound data [number of sites with halos, intima-media thickness (IMT), presence of bilateral halos] at the level of the temporal arteries (TA) and axillary arteries (AX) were assessed. Two systematic literature reviews (SLR) were performed by searching MEDLINE, EMBASE and Cochrane CENTRAL library to inform the European League Against Rheumatism (EULAR) update of the recommendations on the management of LVV. Results. The GCA cohort included 160 patients [female 120 (75%), mean age 72.4±8.2 years]. Sixty-three (39.4%) evaluated with FTA, 97 (60.6%) with conventional approach. Since the introduction of FTA the need for TAB reduced by 93%. Median follow-up duration was shorter in the FTA group compared to the conventional one (0.9 vs. 5.0 years; p<0.001). Permanent visual loss (PVL) occurred in 8 (12.7%) FTA patients and 26 (26.8%) conventional ones (p=0.03). During COVID-19 there was a significant increase in the occurrence of PVL (40%) including bilateral blindness despite a regularly operating FTA clinic. Cumulative incidence of relapses and time to first relapse did not change after FTA introduction. Quantitative ultrasound data were evaluated on 135 GCA patients from TABUL [female 92 (68%), age 73±8 years] and 72 patients from the independent cohort [female 33 (46%), age 75±7 years]. The best-fitting CDS model for TAB used maximum IMT and bilaterality of TA and AX halos. The best-fitting clinical model included raised inflammatory markers, polymyalgia rheumatica, headache and ischaemic symptoms. By combining CDS and clinical models a score to calculate the probability of having a positive TAB, given the ultrasonographic and clinical information, was derived. No significant association was found for prediction of clinical outcome at 6 months. The SLRs confirmed the need to urgently refer the patient to a specialised team, including FTA clinics. The main treatment for LVV remain high-dose GC, however, more evidence has been retrieved to support the use of adjunctive immunosuppressants, including novel biologic treatments for GCA. Conclusion. With our studies we have contributed to clarify the role of novel diagnostic approaches to the disease as part of fast track clinics and supported the role of ultrasound as a reliable diagnostic tool and to significantly reduce the risk of permanent blindness. A quantitative ultrasound analysis (extention and degree of vascular involvement) supported by clinical findings is useful to identify patients with a positive biopsy. Relapse rate and LV-complications did not change upon FTA introduction, highlighting the need for better disease activity monitoring and therapeutic strategies.
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Furu, Moritoshi. "Identification of AFAP1L1 as a prognostic marker for spindle cell sarcomas." Kyoto University, 2011. http://hdl.handle.net/2433/151917.
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Lamp, Ole. "Etablierung biochemischer Marker für Diagnostik und Prognose caniner Mammatumore." Doctoral thesis, Universitätsbibliothek Leipzig, 2012. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-87999.
Full textAbstract:
Canine Mammatumoren (CMT) sind eine der häufigsten Todesursachen bei Hündinnen (SIMON et al. 2001). Durch ihre periphere Lage sind zumeist nicht die Primärtumoren, sondern ihre Metastasen lebensbedrohlich, da diese häufig wichtige Organe wie Lunge Herz und Gehirn befallen (CLEMENTE et al. 2010). Aktuell angewandte Untersuchungsmethoden zur Erkennung von Metastasierung können entweder das invasive Wachstum beschreiben oder bereits bestehende Metastasen detektieren, jedoch fehlen bislang molekulare Marker, die frühzeitig und zuverlässig das metastatische Potential eines CMT anzeigen bevor Metastasen aufgetreten sind. Das Peptidhormon Relaxin ist in zahlreichen physiologischen und pathologischen Situationen beim Menschen als ein Induktor von Matrixmetalloproteinasen (MMP) bekannt (TOO et al. 1984; UNEMORI und AMENTO 1990; PALEJWALA et al. 2001; BINDER et al. 2002; KLONISCH et al. 2007; HENNEMAN et al. 2008). MMP sind Schlüsselenzyme des Bindegewebsabbaus, der jeder Metastasierung vorausgehen muss (WOODHOUSE et al. 1997). Bei der Frau ist im Blut messbares Relaxin ein Marker für metastatischen Brustkrebs (BINDER et al. 2004), für die Hündin scheint dagegen der Relaxinblutspiegel nicht aussagekräftig zu sein (SCHWEIZER 2010). Möglicherweise wird aber Relaxin lokal im caninen Mammagewebe exprimiert wie von GOLDSMITH et al. (1994) und SILVERTOWN et al. (2003) postuliert, so dass es wie in humanen Tumoren auto- oder parakrin Invasivität und Metastasierung (KLONISCH et al. 2007) fördern könnte. Daher sollte in der vorliegenden Arbeit die intratumorale Expression des Relaxins und seiner Rezeptoren sowie bekannter Faktoren des Bindegewebsabbaus untersucht und auf ihre prognostische Eignung überprüft werden. In zwei Studienabschnitten (LAMP et al. 2009; LAMP et al. 2011) wurden CMT-Gewebeproben von n=31 (LAMP et al. 2009) respektive n=59 Hündinnen (LAMP et al. 2011) mittels quantitativer Reverse-Transkriptase-Polymerasekettenreaktion (qRT-PCR) auf ihre Expression von Relaxin, seinen Rezeptoren, RXFP1 und RXFP2, sowie den Matrixmetalloproteinasen MMP-1, -2, -3, -9 und MMP-13, den Östradiolrezeptoren, ERα und ERβ, und dem Progesteronrezeptor (PR) analysiert. In beiden Studienabschnitten wurden die Plasmakonzentrationen der Hormone Relaxin, Östradiol und Progesteron auf mögliche Zusammenhänge mit der lokalen Genexpression überprüft. Im zweiten Studienabschnitt (LAMP et al. 2011) wurde darüber hinaus die Expression von Relaxin und RXFP1 auch immunhistologisch an n=9 CMT-Proben untersucht und in einer Multivarianzanalyse die prognostische Eignung aller untersuchten Parameter getestet. Die Expressionsanalyse konnte zeigen, dass CMT sowohl ein bisher unbekannter Ort der Relaxinexpression beim Hund sind als auch den Hauptrezeptor des Relaxins, RXFP1, exprimieren. Diese Ergebnisse der mRNA-Untersuchung ließen sich immunhistologisch bestätigen. Darüber hinaus ergab die immunhistologische Untersuchung, dass Relaxin vorwiegend im myoepithelialen Anteil der untersuchten CMT exprimiert wird. In den epithelialen CMT-Zellen fand sich die stärkste RXFP1-Reaktivität, so dass RXFP1 mit der von anderen Autoren beschriebenen MMP-2- und MMP-9-Expression in epithelialen Zellen kolokalisiert ist (PAPPARELLA et al. 1997; HIRAYAMA et al. 2002; PAPPARELLA et al. 2002). Die quantitativen Expressionsanalysen zeigten Korrelationen der Expressionsintensitäten von Relaxin, RXFP1 und MMP-2 auf. Die RXFP1 Expression war in dieser Studie sogar ein unabhängiger Marker für Metastasierung mit einem 15-fach höheren Risiko für Metastasierung für Patienten mit einer Expression oberhalb des studienspezifischen Cut-Offs. Alle untersuchten lokalen Genexpressionen waren von den systemischen Plasmakonzentrationen von Relaxin, Östradiol und Progesteron unabhängig. Die Resultate legen eine Bedeutung des intratumoral exprimierten Relaxins für eine auto- oder parakrine Steuerung der MMP-Expression, die für Invasivität und Metastasierung wichtig ist, nahe. Aufgrund des mRNA-Nachweises, der Kolokalisation der Proteine von RXFP1 und MMP-2 und -9 sowie der Korrelation der Genexpression von Ligand (Relaxin), Rezeptor (RXFP1) und Effektormolekül (MMP-2) ist es wahrscheinlich, dass CMT über das Relaxin eine autonome Steuerung ihrer Invasivität vornehmen können. RXFP1 scheint dabei eine Regulationsfunktion in der Relaxinsensibilität der CMT-Zelle zuzukommen, die in Zukunft durch die Messung der RXFP1-Expressionsintensität prognostisch nutzbar sein könnte. Zudem ist RXFP1 im CMT damit auch ein möglicher Ansatzpunkt für eine neue, auf Relaxinanaloga basierende, antimetastatische Therapie, die bereits an humanen Tumorzellen und in Mausmodellen erprobt wird (FENG et al. 2007; HOSSAIN et al. 2010). Durch den Nachweis von Relaxin und RXFP1 im CMT und ihre wahrscheinliche Relevanz für die Metastasierung ergeben sich somit neue Möglichkeiten für eine exaktere Prognose und verbesserte antimetastatische Therapie von CMT sowie die Chance, den Hund als Modell für die Erforschung Relaxin basierter Therapien des humanen Brustkrebses zu nutzenCanine mammary tumours (CMT) are one of the main reasons of death in female dogs (SIMON et al. 2001). Due to its peripheral location, it is normally not the primary tumour, but its metastases, which are life-threatening as they often impair the function of vital organs, such as lung, heart or brain (CLEMENTE et al. 2010). Currently used techniques for the detection of metastasis can either barely describe invasive growth patterns or detect already existing metastases. Molecular markers to determine the metastatic potential early and reliably, before metastatic spreading has occurred, are still lacking. The peptide hormone relaxin is well known as an inductor of matrix metalloproteinases (MMP) in numerous physiological as well as pathological situations in humans (TOO et al. 1984; UNEMORI und AMENTO 1990; PALEJWALA et al. 2001; BINDER et al. 2002; KLONISCH et al. 2007; HENNEMAN et al. 2008). MMP are key-enzymes of connective tissue remodelling which is a prerequisite for metastasis (WOODHOUSE et al. 1997). In women, the plasma relaxin concentration is a marker for metastatic breast cancer (BINDER et al. 2004). However, in dogs, the concentration of circulating relaxin seems to have no diagnostic value (SCHWEIZER 2010). But, possibly relaxin is expressed locally in the canine mammary tissue as postulated by GOLDSMITH et al. (1994) and SILVERTOWN et al. (2003) and it could therefore act as a pro-invasive and pro-metastatic factor in an auto- or paracrine manner as it does in various human tumours (KLONISCH et al. 2007). Thus, the present study should examine the intratumoural expression of relaxin and its receptors as well as factors of connective tissue remodelling and evaluate their prognostic abilities. In two sections of the study (LAMP et al. 2009; LAMP et al. 2011), CMT-tissue samples from n=31 bitches (LAMP et al. 2009) and n=59 bitches (LAMP et al. 2011), respectively, were analysed for their expression of relaxin, its receptors RXFP1 and RXFP2, MMP-1, -2, -3, -9 and MMP-13 as well as the oestradiol receptors ERα and ERβ and the progesterone receptor (PR) using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Additionally, the plasma concentrations of the hormones relaxin, oestradiol and progesterone were tested for possible connections with the local gene expression. In the second section of the study, the expression of relaxin and RXFP1 was also examined immunohistologically in n=9 CMT tissue samples (LAMP et al. 2011) and the prognostic value of all parameters examined was assessed by a multivariate analysis. The expression analysis showed that CMTs are a novel site of expression of relaxin and its main receptor RXFP1 in the dog. These results were confirmed by the immunohistological examination. Moreover, the immunohistological analysis demonstrated that relaxin seems to be expressed mainly in myoepithelial cells. However, the strongest signals for RXFP1 were located in epithelial cells of the CMT, thus RXFP1 is colocalised with the expression of MMP-2 and MMP-9 reported in epithelial CMT-cells (PAPPARELLA et al. 1997; HIRAYAMA et al. 2002; PAPPARELLA et al. 2002). The quantitative expression analysis revealed correlations of expression intensities for relaxin, RXFP1 and MMP-2. The expression of RXFP1 presented as an independent marker for metastasis with a 15-fold risk increase for patients with an expression intensity above the study-specific cut-off. All local gene expressions examined where independent from systemic plasma concentrations of relaxin, oestradiol and progesterone. The results propose an important role for intratumourally expressed relaxin as an auto- or paracrine modulator of MMP expression, which is important for invasiveness and metastasis. Due to the mRNA detection, the protein colocalisation of RXFP1 with MMP-2 and MMP-9 as well as the correlation of gene expressions of the ligand (relaxin), the receptor (RXFP1) and the effector (MMP-2) it is highly probable that CMT can autonomously regulate their invasiveness via locally expressed relaxin. RXFP1 seems to have a regulatory function in the relaxin responsiveness of CMT cells, which may be of prognostical use in the future. In addition, RXFP1 is also a possible target for a novel antimetastatic therapy based on relaxin analoga which has been tested in human tumour cells and mice (FENG et al. 2007; HOSSAIN et al. 2010). The detection of relaxin and RXFP1 in the CMT and their probable relevance for metastasis could be a basis for a more precise prognosis of CMT, improved anti-metastatic therapies in the dog and the use of the dog as a model for relaxin-based therapies of human breast cancer
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Barlas, Irtaza. "A Multiagent Framework for a Diagnostic and Prognostic System." Diss., Georgia Institute of Technology, 2003. http://hdl.handle.net/1853/5290.
Full textAbstract:
A Multiagent Framework for a Diagnostic and Prognostic System
Irtaza Barlas
124 Pages
Directed By: Dr. George Vactsevanos
The shortcomings of the current diagnostic and prognostic systems stem from the limitations of their frameworks. The framework is typically designed on the passive, open loop, static, and isolated notions of diagnostics, in that the framework does not observe its diagnostic results (open-looped), hence can not improve its performance (static). Its passivity is attributed to the fact that an external event triggers the diagnostic or prognostic action. There is also no effort in place to team-up the diagnostic systems for a collective learning, hence the implementation is isolated.
In this research we extend the current approaches of the design and implementation of diagnostic and prognostic systems by presenting a framework based upon Multiagent systems. This research created novel architectures by providing such unique features to the framework, as learning, reasoning, and coordination. As the primary focus of the research the concept of Case-Based Reasoning was exploited to reason in the temporal domain to generate better prognosis, and improve the accuracy of detection as well as prediction. It was shown that the dynamic behavior of the intelligent agent helps it to learn over time, resulting in improved performance.
An analysis is presented to show that a coordinated effort to diagnose also makes sense in uncertain situations when there are certain number of systems attempting to communicate certain number of failures, since there can be high probability of finding a shareable experience.
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Zhang, Guangfan. "Optimum Sensor Localization/Selection In A Diagnostic/Prognostic Architecture." Diss., Georgia Institute of Technology, 2005. http://hdl.handle.net/1853/6846.
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Optimum Sensor Localization/Selection in
A Diagnostic/Prognostic Architecture
Guangfan Zhang
107 Pages
Directed by Dr. George J. Vachtsevanos
This research addresses the problem of sensor localization/selection for fault diagnostic purposes in Prognostics and Health Management (PHM)/Condition-Based Maintenance (CBM) systems. The performance of PHM/CBM systems relies not only on the diagnostic/prognostic algorithms used, but also on the types, location, and number of sensors selected. Most of the research reported in the area of sensor localization/selection for fault diagnosis focuses on qualitative analysis and lacks a uniform figure of merit. Moreover, sensor localization/selection is mainly studied as an open-loop problem without considering the performance feedback from the on-line diagnostic/prognostic system. In this research, a novel approach for sensor localization/selection is proposed in an integrated diagnostic/prognostic architecture to achieve maximum diagnostic performance.
First, a fault detectability metric is defined quantitatively. A novel graph-based approach, the Quantified-Directed Model, is called upon to model fault propagation in complex systems and an appropriate figure-of-merit is defined to maximize fault detectability and minimize the required number of sensors while achieving optimum performance.
Secondly, the proposed sensor localization/selection strategy is integrated into a diagnostic/prognostic system architecture while exhibiting attributes of flexibility and scalability. Moreover, the performance is validated and verified in the integrated diagnostic/prognostic architecture, and the performance of the integrated diagnostic/prognostic architecture acts as useful feedback for further optimizing the sensors considered. The approach is tested and validated through a five-tank simulation system.
This research has led to the following major contributions:
??generalized methodology for sensor localization/selection for fault diagnostic purposes.
??quantitative definition of fault detection ability of a sensor, a novel Quantified-Directed Model (QDG) method for fault propagation modeling purposes, and a generalized figure of merit to maximize fault detectability and minimize the required number of sensors while achieving optimum diagnostic performance at the system level.
??novel, integrated architecture for a diagnostic/prognostic system.
??lidation of the proposed sensor localization/selection approach in the integrated diagnostic/prognostic architecture.
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Maddison, John. "Digital image processing for prognostic and diagnostic clinical pathology." Thesis, University of Huddersfield, 2005. http://eprints.hud.ac.uk/id/eprint/22322/.
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When digital imaging and image processing methods are applied to clinical diagnostic and prognostic needs, the methods can be seen to increase human understanding and provide objective measurements. Most current clinical applications are limited to providing subjective information to healthcare professionals rather than providing objective measures. This Thesis provides detail of methods and systems that have been developed both for objective and subjective microscopy applications. A system framework is presented that provides a base for the development of microscopy imaging systems. This practical framework is based on currently available hardware and developed with standard software development tools. Image processing methods are applied to counter optical limitations of the bright field microscope, automating the system and allowing for unsupervised image capture and analysis. Current literature provides evidence that 3D visualisation has provided increased insight and application in many clinical areas. There have been recent advancements in the use of 3D visualisation for the study of soft tissue structures, but its clinical application within histology remains limited. Methods and applications have been researched and further developed which allow for the 3D reconstruction and visualisation of soft tissue structures using microtomed serial histological sections specimens. A system has been developed suitable for this need is presented giving considerations to image capture, data registration and 3D visualisation, requirements. The developed system has been used to explore and increase 3D insight on clinical samples. The area of automated objective image quantification of microscope slides presents the allure of providing objective methods replacing existing objective and subjective methods, increasing accuracy and rsducinq manual burden. One such existing objective test is DNA Image Ploidy which seeks to characterise cancer by the measurement of DNA content within individual cell nuclei, an accepted but manually burdensome method. The main novelty of the work completed lies in the development of an automated system for DNA Image Ploidy measurement, combining methods for automatic specimen focus, segmentation, parametric extraction and the implementation of an automated cell type classification system. A consideration for any clinical image processing system is the correct sampling of the tissue under study. VVhile the image capture requirements for both objective systems and subjective systems are similar there is also an important link between the 3D structures of the tissue. 3D understanding can aid in decisions regarding the sampling criteria of objective tests for as although many tests are completed in the 2D realm the clinical samples are 3D objects. Cancers such as Prostate and Breast cancer are known to be multi-focal, with areas of seeming physically, independent areas of disease within a single site. It is not possible to understand the true 3D nature of the samples using 2D micro-tomed sections in isolation from each other. The 3D systems described in this report provide a platform of the exploration of the true multi focal nature of disease soft tissue structures allowing for the sampling criteria of objective tests such as DNA Image Ploidy to be correctly set. For the Automated DNA Image Ploidy and the 3D reconstruction and visualisation systems, clinical review has been completed to test the increased insights provided. Datasets which have been reconstructed from microtomed serial sections and visualised with the developed 3D system area presented. For the automated DNA Image Ploidy system, the developed system is compared with the existing manual method to qualify the quality of data capture, operational speed and correctness of nuclei classification. Conclusions are presented for the work that has been completed and discussion given as to future areas of research that could be undertaken, extending the areas of study, increasing both clinical insight and practical application.
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Lindbäck, Stefan. "Primary HIV-1 infection : diagnostic, prognostic, and therapeutic aspects /." Stockholm, 1999. http://diss.kib.ki.se/1999/91-628-3606-4/.
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Corso, Giovanni. "Searching for novel diagnostic-prognostic biomarkers in gastric cancer." Doctoral thesis, Faculdade de Medicina da Universidade do Porto, 2011. http://hdl.handle.net/10216/62210.
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Chapman, P. J. "Diagnostic, prognostic and therapeutic considerations in primary pulmonary hypertension." Master's thesis, University of Cape Town, 1987. http://hdl.handle.net/11427/25726.
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The diagnosis of primary pulmonary hypertension (PPH) and prediction of its course, whether treated or untreated, presents several problems. These are of particular relevance when selection of patients for, and timing of heart-lung transplantation is being considered. I performed a retrospective study on patients with PPH and chronic large vessel thromboembolic pulmonary hypertension (TPH) seen at Groote Schuur Hospital between 1957 and 1985 in an attempt to: 1. Establish the diagnostic and prognostic value of clinical features, lung function tests, cardiac catheterisation, isotope lung scans and, in the PPH group, response to therapy; 2. Review our experience of the effects of treatment with vasodilators and oral anticoagulants, and the results of heart and lung transplantation in the PPH group; 3. Attempt to identify features which could be used to predict prognosis in PPH; and thereby 4. Define criteria for selecting PPH patients whose prognosis could be improved by heart-lung transplantation.
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Fargus, Alexander. "Optimisation of correlation matrix memory prognostic and diagnostic systems." Thesis, University of York, 2015. http://etheses.whiterose.ac.uk/9032/.
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Condition monitoring systems for prognostics and diagnostics can enable large and complex systems to be operated more safely, at a lower cost and have a longer lifetime than is possible without them. AURA Alert is a condition monitoring system that uses a fast approximate k-Nearest Neighbour (kNN) search of a timeseries database containing known system states to identify anomalous system behaviour. This search algorithm, AURA kNN, uses a type of binary associative neural network called a Correlation Matrix Memory (CMM) to facilitate the search of the historical database. AURA kNN is evaluated with respect to the state of the art Locality Sensitive Hashing (LSH) approximate kNN algorithm and shown to be orders of magnitude slower to search large historical databases. As a result, it is determined that the standard AURA kNN scales poorly for large historical databases. A novel method for generating CMM input tokens called Weighted Overlap Code Construction is presented and combined with Baum Coded output tokens to reduce the query time of the CMM. These modifications are shown to improve the ability of AURA kNN to scale with large databases, but this comes at the cost of accuracy. In the best case an AURA kNN search is 3.1 times faster than LSH with an accuracy penalty of 4% on databases with 1000 features and fewer than 100,000 samples. However the modified AURA kNN is still slower than LSH with databases with fewer features or more samples. These results suggest that it may be possible for AURA kNN to be improved so that it is competitive with the state of the art LSH algorithm.
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Corso, Giovanni. "Searching for novel diagnostic-prognostic biomarkers in gastric cancer." Tese, Faculdade de Medicina da Universidade do Porto, 2011. http://hdl.handle.net/10216/62210.
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Vereecken, Pierre. "Contribution to the study of diagnosis and prognosis of cutaneous melanoma: is Galectin-3 a relevant biomarker ?" Doctoral thesis, Universite Libre de Bruxelles, 2008. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210417.
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La galectine-3 (Gal-3), protéine de type lectine, de 29-35 kDa, étudiée comme marqueur d’aggressivité dans les gliomes, présente des caractéristiques biologiques importantes justifiant son étude dans le domaine du mélanome. En effet, la Gal-3 est une protéine qui peut se lier à la laminine, tout comme l’intégrine α6/β1 dont l’expression est réduite dans le mélanome. L’expression de cette intégrine peut d’ailleurs être modulée par la Gal-3 comme récemment montré dans des lignées cellulaires de cancer du sein (BT-549) et de glioblastome (U373).Le mélanome, véritable problème de santé publique qui est susceptible d’atteindre 1 individu sur 75 dans nos contrées, reste un tumeur mal comprise avec des évolutions parfois incertaines, et des traitements dont l’efficacité est limitée. Le diagnostic histologique du mélanome lui-même peut parfois représenter une difficulté pour le clinicien et l’expert pathologiste ou dermatopathologiste. La couleur (hyperpigmentation d’un lésion pigmentée), dont l’évaluation d’ailleurs reste subjective à défaut de standardisation, ne peut à elle seule signer la malignité d’une lésion pigmentée. Globalement l’évolution d’un patient est prédite par l’indice de Breslow qui traduit en mm l’épaisseur de la tumeur. Si cet indice dépasse 1mm, le risque métastatique augmente, justifiant la réalisation de bilans extensifs de suivi. Ceci dit, certains mélanomes épais peuvent ne pas présenter de caractéristiques d’aggressivité, alors que des mélanomes fins sont parfois mortels. L’identification de marqueurs moléculaires est donc impérative, tant pour développer des stratégies thérapeutiques ciblées, que pour affiner le diagnostic et le pronostic d’un patient.
Après avoir mis en évidence par immunohistochimie une expression de Gal-3 par les mélanocytes, nous avons démontré une surexpression de cette protéine par les mélanocytes tumoraux. Nous avons démontré également sur des lésions primitives qu’à l’aggressivité mesurée selon l’indice de Breslow correspondait une diminution de cette surexpression. Cette observation a pu être confirmée par un modèle de greffe orthotopique chez la souris nude.
Nous nous somme intéressés par la suite à la détection de la protéine dans le sérum, et nous avons constaté, un taux élevé de Gal-3 dans le sérum de patients en stade métastatique avancé, ce taux élevé pouvant s’expliquer tant par la charge tumorale que par la présence d’une inflammation, d’ailleurs bien connue chez le patient cancéreux en stade avancé. Le rôle antiapoptotique de la Gal-3 nous a alors amené à préciser la valeur prédictive et pronostique de cette protéine. L’hypothèse d’une potentielle action bénéfique sur la réponse immunitaire des patients atteints de mélanome qui ont été vaccinés a été rejetée. La Gal-3 sérique s’est révélée comme facteur de mauvais pronostic chez les patients métastatiques, et une analyse multivariée avec la définition d’une valeur « cut-off » de 10 ng/ml a permis de montrer une valeur pronostique indépendante, supérieure à la S100B et à la CRP.
Doctorat en Sciences médicales
info:eu-repo/semantics/nonPublished
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Chana, Jagdeep. "The prognostic and therapeutic significance of C-MYC expression in melanoma." Thesis, Imperial College London, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.314348.
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Teppo, H. (Heikki). "Incidence, survival, diagnostic delays and prognostic factors in laryngeal cancer." Doctoral thesis, University of Oulu, 2003. http://urn.fi/urn:isbn:9514271262.
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Abstract
Incidence trends of laryngeal cancer in Finland were analyzed, especially in relation to survival, in a patient series of 5766 patients diagnosed in 1956–1995 and identified from the Finnish Cancer Registry. The age-adjusted incidence rate decreased from 6.5 to 3.5 per 100 000 person-years in males and remained unchanged among females. Only minor improvement occurred in survival. In a hospital-based material from Northern Finland (353 patients with laryngeal squamocellular carcinoma, LSCC, diagnosed in 1976–1995), the incidence among males decreased only for supraglottic cancer, diminishing the supraglottic to glottic incidence ratio from 1.4:1 to 0.5:1.
Evaluation of diagnostic delays and their impact on survival and risk of recurrence was undertaken in a sample of 66 LSCC patients. In only 38% of the patients was malignancy suspected at the initial visit to a physician; infection was the most common misdiagnosis (41%). Half of the first consultations resulted in referral, whereas 17% of the patients were neither referred nor controlled. The median patient delay was 2 months and median professional delay 3 months. The latter exceeded 12 months in 17% of the patients. The delays were not significantly related to any other clinical parameter, nor were they interrelated. Professional delay of 12 months or more resulted in increased relative hazard of death (HR = 4.74, p = 0.05), equalling the effect of advanced stage (stage IV).
One-third of the patients developed a recurrence. In univariate analysis, professional delay of 12 months or more increased the risk of local (p = 0.019) and neck (p = 0.019) recurrence. In a multivariate model, professional delay of 12 months or more indicated an adjusted relative hazard ratio (HR) of 4.6 for local recurrence (p = 0.02) and 9.5 for neck recurrence (p = 0.015).
Immunohistochemical factors p53, apoptosis, angiogenesis and proliferation were included in a multivariate model evaluating prognostic factors of LSCC in addition to clinical and sociodemographic factors. Advanced stage (stages III–IV) (relative hazard ratio of death (HR) 8.9, p = 0.01), supraglottic site (HR 5.6, p = 0.02) and high apoptotic index (≥ 0.3) (HR 11.1, p = 0.05) were the best indicators of impaired prognosis.
Professional delay and enhanced apoptotic rate could be helpful in selecting LSCC patients for more aggressive primary treatment.
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Baba, Tsukasa. "Trophinin is a potent prognostic marker of ovarian cancer involved in platinum sensitivity." Kyoto University, 2007. http://hdl.handle.net/2433/135775.
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Manita, Muftah. "The prognostic value of perfusion MRI in cerebral glioma." Thesis, University of Nottingham, 2012. http://eprints.nottingham.ac.uk/12776/.
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Introduction Cerebral glioma is the most prevalent primary brain tumour, of which the majority are high grade gliomas. High grade gliomas possess a poor prognosis, and glioblastoma patients survive less than one year after diagnosis. To date, histological grading is used as the standard technique for diagnosis and survival prediction. Previous studies using advanced techniques such as MR Perfusion have achieved a high sensitivity but a low specificity in identifying high grade gliomas. Moreover, they have failed to distinguish glioblastoma from anaplastic glioma. The purpose of the study presented here is to assess the diagnostic and prognostic value for cerebral glioma of cerebral blood volume maps derived from MR perfusion. Methods This retrospective study was approved by the local research ethics committee and clinical audit office. This study included 123 patients with newly diagnosed cerebral glioma, of all grades. Histological diagnosis was used as the standard reference for all potential patients. The relative tumour blood volume (rTBVmax) derived from MR perfusion was used for radiological grading of cerebral glioma. Receiver operating characteristics (ROC) were used to define the best threshold value in distinguishing the glioma grades and in determining the accuracy values (sensitivity, specificity, and positive and negative predictive values). For survival analysis, Kaplan-Meier was used to illustrate and compare the discriminatory value of the histological and radiological classifications. A multiple Cox regression model was used to assess the prognostic value of both classifications in addition to other tested demographic and clinical variables. Finally, the influence of potential moderators was assessed using ANOVA, to assess whether the variation in rTBVmax was only due to the difference in tumour grades. Results A model data set (n = 50) produced a 7-fold increase of TBVmax in tumour versus white matter and provided sensitivity and specificity of 97% and 94%, respectively, in distinguishing high versus low grade glioma. Moreover, a threshold value of 9.6 provided sensitivity and specificity of 100% and 56% in differentiating glioblastoma within the group of high grade gliomas. These threshold values were applied to the second group (n = 73) and provided sensitivity and specificity of 96% and 95% in distinguishing high versus low grade glioma, and 97% and 73% in differentiating, within the high grade gliomas, glioblastoma from anaplastic glioma. Using these two thresholds for a three-tier radiological classification, both the Kaplan-Meier plots and the multiple Cox regression showed that radiological classification was the most independent predictor of survival and tumour progression. The proposed radiological classification system was better than histological classification in predicting glioma patients survival especially noted in a group of moderately hyperaemic rTBVmax. Conclusion MR perfusion is a non-invasive and robust technique in glioma grading and survival prediction. The diagnostic value of rTBVmax derived from MR perfusion in differentiating high versus low grade glioma is promising. It may have a role in the future in defining the appropriate treatment. However, the proposed radiological classification was inferior in differentiating anaplastic glioma from glioblastoma multiforme. In the future, a more advanced multimodal MR, such as MR spectroscopy and MR diffusion, may be studied, besides MR perfusion, in order to improve this diagnostic accuracy.
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Rosunally, Yasmine Zaina. "Diagnostic and prognostic analysis tools for monitoring degradation in aged structures." Thesis, University of Greenwich, 2012. http://gala.gre.ac.uk/8785/.
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This research addresses the problem of prolonging the life of aged structures of historical value that have already outlived their original designed lives many times. While a lot of research has been carried out in the field of structural monitoring, diagnostics and prognostics for high tech industries, this is not the case for historical aged structures. Currently most maintenance projects for aged structures have focused on the instrumentation and diagnostic techniques required to detect any damage with a certain degree of success. This research project involved the development of diagnostic and prognostic tools to be used for monitoring and predicting the ‘health’ of aged structures. The diagnostic and prognostic tools have been developed for the monitoring of Cutty Sark iron structures as a first application. The concept of canary and parrot sensor devices are developed where canary devices are small, accelerated devices, which will fail according to similar failure mechanisms occurring in an aged structures and parrot devices are designed to fail at the same rate as the structure, thus mimicking the structure. The model-driven prognostic tool uses a Physics-of-Failure (PoF) model to predict remaining life of a structure. It uses a corrosion model based on the decrease in corrosion rate over time to predict remaining life of an aged iron structures. The data-driven diagnostic tool developed uses Mahalanobis Distance analysis to detect anomalies in the behaviour of a structure. Bayesian Network models are then used as a fusion method, integrating remaining life predictions from the model-driven prognostic tool with information of possible anomalies from data-driven diagnostic tool to provide a probability distribution of predicted remaining life. The diagnostics and prognostic tools are validated and tested through demonstration example and experimental tests. This research primarily looks at applying diagnostic and prognostic technologies used in high-tech industries to aged iron structures. In order to achieve this, the model-driven and data-driven techniques commonly used had to be adapted taking into consideration the particular constraints of monitoring and maintaining aged structures. The fusion technique developed is a novel approach for prognostics for aged structures and provides the flexibility often needed for diagnostic and prognostic tools.
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Forder, Michael David. "Crohn's Disease : diagnostic and prognostic indicators with special reference to granulomas." Master's thesis, University of Cape Town, 1992. http://hdl.handle.net/11427/25570.
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The fact therefore remains that, at the present time, Crohn's disease is still an enigma. The aetiology and pathogenesis are obscure, the clinical findings and progression of the disease are unpredictable and the histological findings are often nonspecific. With this in mind, this dissertation attempts to define and document the incidence of certain histological features at presentation in a population of Crohn's disease patients from Groote Schuur Hospital. The main aim is to determine the incidence of granulomas in the study group as a whole, as well as to establish the distribution of granulomas within the bowel. A correlation between the presence of granulomas and the clinical activity of the disease (as assessed by the Crohn's Disease Activity Index) is also sought.
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Hewamana, Saman. "Prospective analysis of NF-kappaB as a superior prognostic marker in chronic lymphocytic leukaemia." Thesis, Cardiff University, 2008. http://orca.cf.ac.uk/55786/.
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In this study, I characterized basal NF-kappaB DNA binding in CLL samples and investigated the value of NF-kappaB as a prognostic marker and therapeutic target in CLL. In contrast to the previous studies, I demonstrated wide heterogeneity in basal NF-kappaB DNA binding among patients which was associated with in vitro survival (P = 0.01) with high white cell count (P = 0.01) and shorter lymphocyte doubling time (P = 0.01). Subunit analysis revealed that in primary CLL cells the principal components were p50, Rel A, and c-Rel. I next investigated the cytotoxicity of a putative NF-kappaB inhibitor, LC-1, and elucidated its mechanism of action in CLL patient samples. LC-1 induced apoptosis with a mean LD50 of 2.9muM after 24 hours normal B and T-cells were significantly more resistant to its apoptotic effects (P <0.001). Apoptosis was associated with caspase-3 activation that was mediated via the upstream activation of both caspase-8 and caspsase-9. Apoptosis was preceded by a reduction of nuclear Rel A DNA binding and down regulation of the anti-apoptotic NF-kappaB target genes CFLAR, BIRC5 and BCL2. LC-1 was highly synergistic with fludarabine (mean combination index 0.26). Rel A DNA binding was strongly associated with advanced Binet stage (P<0.0001) but did not correlate with lgVH mutation status (P = 0.25), CD38 expression (P = 0.87) or ZAP-70 expression (P = 0.55). In addition, it was predictive of time to first treatment (P = 0.02) and time to subsequent treatment (P = 0.0001). Indeed, Rel A was the most predictive marker of survival both from date of diagnosis (hazard ratio 9.1, P = 0.01) and date of entry into the study (hazard ratio 3.9, P = 0.05). Taken together, the data suggests that NF-kB is a promising therapeutic target and prognostic marker in CLL. Prospective clinical trials designed to evaluate these conclusions are clearly now warranted.