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Effect of Drug Switching on Lower Urinary Tract Dynamics and Quality of Life in Patients with Overactive Bladder
Holub, Lukáš ; Broďák, Miloš (advisor) ; Záleský, Miroslav (referee) ; Vidlář, Aleš (referee)
The aim of this dissertation is to evaluate the effect of solifenacin on quality of life (QoL) of patients previously treated with another antimuscarinic for overactive bladder (OAB) and to compare the effects of solifenacin according to previous antimuscarinic treatment. The study evaluated a representative sample of the OAB population (2,000 patients enrolled in 60 centres in the Czech Republic, 1,481 patients completed all five trials and 1,892 patients had a baseline and at least one post-treatment assessment). Methods for validation were treatment satisfaction questionnaires: the Perceived Satisfaction with Treatment Questionnaire (TS VAS), the short form of the Overactive Bladder Questionnaire (OAB q SF) and the European Quality of Life Questionnaire (EuroQoL - EQ-5D-5L). Improvements in QoL and OAB symptoms were observed over 12 months in a population of patients treated with solifenacin 5-10 mg and previously treated with other antimuscarinics. The development of OAB total score was not significantly (p = 0.45) affected by previous treatment. OAB q SF scores, including the total HRQoL score, all HRQoL subgroups and symptom severity scores, improved over the follow-up period. Changes in TS VAS scores also showed improvement in overall QoL during the study period. EQ-5D-5L showed a shift...
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Role of Pregnancy-associated Proteins and other Biomarkers in Diagnostics and Pediction of Prognosis of Renal Cell Carcinoma
Čechová, Marcela ; Babjuk, Marek (advisor) ; Broďák, Miloš (referee) ; Hartmann, Igor (referee)
Role of Pregnancy-associated Proteins and other Biomarkers in Diagnostics and Prediction of Prognosis of Renal Cell Carcinoma Abstract The work describes the role of pregnancy-associated proteins, pregnancy-associated plasma protein A (PAPP-A) and placental growth factor (PlGF), in relation to renal cell carcinoma (RCC) and their possible use as a biomarkers of this tumour. The theoretical part of the thesis summarizes the essential knowledge of RCC focused on prognostic factors of this malignancy and provides a comprehensive overview of potential biomarkers. In the experimental part serum concentrations of PAPP-A and PlGF in patients operated for clear cell RCC were evaluated and their potential value in diagnostics and prediction of prognosis of subjects with this most frequent histological subtype of RCC was assessed. Furthermore, the thesis evaluates the relation of selected single nucleotide polymorphisms of PAPP-A gene [C/G SNP (rs13290387) a Cys327Cys SNP (rs12375498)] to the most common histological subtypes of RCC (clear cell, papillary I and II type, chromophobe) and oncocytoma. Based on our results, PAPP-A does not seem to be a suitable marker for diagnosis or evaluation of prognosis in patients with ccRCC, however, PlGF appears to be a potential diagnostic and prognostic marker of this disease....
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Non-invasive diagnosis of urothelial carcinoma of the urinary bladder by evaluation of cell-free DNA and microRNA in urine
Brisuda, Antonín ; Babjuk, Marek (advisor) ; Hora, Milan (referee) ; Broďák, Miloš (referee)
Bladder cancer represents the most common malignancy of the uropoetic tract. Its incidence has been stable in the last couple of years in the Czech Republic, worldwide rises though. A ratio of incidence and mortality is considerable in bladder cancer since it is highest out of all genitourinary malignancies. An early diagnosis and adequate treatment is therefor determinig for its prognosis. There are several commercialy available urine tests, none of them is recommended as a standard diagnostic tool in any indication though. Urine cytology, as a complement of invasive cystoscopy, remains the only widely used method with all its limitations. Cell-free nucleic acids in urine (urine supernatant) belong amongs potential tumour biomarkers. Cell-free urinary DNA (ucfDNA) is excreted by cells undergoing necrosis or apoptosis although it can also originate from living cells. Their level in urine or serum can thus indicate a presence of malignancy. Micro RNA (miRNA) are short non-coding sequences of RNA produced outside of nucleus. They bind to complementary sequences of mRNA thus affecting its translation and protein formation. As such they play an important role in cell division and cancerogenesis. In our study, we correlated levels of ucfDNA in controls and patients with urothelial carcinoma of different...
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Impact of Warm Ischemia on Renal Function - Clinical Model of Tumor Resection of Solitary Kidney
Stránský, Petr ; Hora, Milan (advisor) ; Broďák, Miloš (referee) ; Doležel, Jan (referee)
Objective: The aim of this work is to evaluate the effect of warm ischemia on renal function. Methods: Within a multicentric study, the data about tumor-affected solitary kidney were obtained from 9 urological centers in the Czech Republic. Patients were divided into groups according to the WIT (warm ischemia time). In each group the mean preoperative serum creatinine was determined, as well as on 3rd and 7th postoperative day and the lowest GF postoperatively. In each group the mean R.E.N.A.L. nephrometric score was determined. Results: The study compriese data totally of 97 patients. The open approach was chosen in 78 cases, in 16 cases laparoscopic approach was chosen. The robotic surgery was performed in 3 patients. PN with zero ischemia was performed in 29 patients (30%). Conclusion: Our findings confirm that non-clamping partial nephrectomy in a solitary kidney minimizes renal injury. For the non-clamping partial nephrectomy can be mainly indicated smaller exophyticall tumors without deep parenchymal invasion. Unfortunately, most of PN should be performed with vascular clamping, allowing precise closure of collecting system, vascular and parenchymal defect, especially for larger tumors with deep parenchymal invasion. According to our observation that WIT of 15 minutes for a kidney is safe. Clamping of...
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Surgical models of the study of the pro-inflammatory effect of adipose tissue in the development of atherosclerosis
Thieme, Filip ; Froněk, Jiří (advisor) ; Vrablík, Michal (referee) ; Broďák, Miloš (referee)
Univerzita Karlova v Praze 1. lékařská fakulta Doktorský studijní program Studijní obor: Experimentální chirurgie MUDr. Filip Thieme Název závěrečné práce Chirurgické modely studia proinflamačního vlivu tukové tkáně v rozvoji aterosklerózy Title Surgical models of the study of the pro-inflammatory effect of adipose tissue in the development of atherosclerosis Typ závěrečné práce Disertační Školitel: doc. MUDr. Jiří Froněk, Ph.D., FRSC Konzultant doc. MUDr. Libor Janoušek, Ph.D. Klinika transplantační chirurgie, IKEM Praha, 2021 Abstract Background: Atherosclerosis is a serious inflammatory systemic disease. Surgery mainly addresses its vascular complications. Conversely, surgery may also lead to the development and acceleration of atherosclerosis, e.g., in a living kidney donor. This would especially be the case in a donor who meets internationally recognized donation criteria but suffers from metabolic syndrome. The effort to refine assessments of living kidney donors in terms of eliminating the risk of developing atherosclerosis is a long-term project. Our aim is to determine risk factors for living kidney donors and to prevent long-term complications after donation. Collecting tissue from a living donor involves not oly subcutaneous tissue (SCAT) but also visceral (VAT) and perivascular tissue (PVAT),...
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The possibility of setting diagnostic and therapeutic algorithms for screening and effective treatment of kidney tumours as prevention of treatment failure.
Klézl, Petr ; Grill, Robert (advisor) ; Broďák, Miloš (referee) ; Záťura, František (referee)
Renal cell carcinoma (RCC) is the third most common urological malignancy, in which about 30% are diagnosed with a metastatic disease at the time of diagnosis. Due to radiation resistance and chemoresistance, the prognosis of these patients is poor. Therefore, the optimal treatment is complete removal of the tumor from at the stage of localized disease. The prognosis of patients has improved in recent decades due to an increase in the number of incidentally detected kidney tumors and also the introduction of new types of treatments. Given the general trend of increasing randomly diagnosed kidney tumors, we were inspired to evaluate patients operated for kidney cancer with respect to the type of disease detection and the method of primary examination. The fact that we do not have a biomarker corresponding to the treatment or recurrence of the disease for monitoring patients after kidney cancer surgery led us to the CTC investigation. CTC examination belongs to the group of liquid biopsy tests and one of its main advantages is the relatively minimal invasiveness (blood collection), which really allows monitoring of tumor dynamics. The primary question was whether CTC cells could play a role in monitoring patients after surgery and event. In the setting of immunotherapeutic and antiangiogenic treatment...
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Non-invasive diagnosis of urothelial carcinoma of the urinary bladder by evaluation of cell-free DNA and microRNA in urine
Brisuda, Antonín ; Babjuk, Marek (advisor) ; Hora, Milan (referee) ; Broďák, Miloš (referee)
Bladder cancer represents the most common malignancy of the uropoetic tract. Its incidence has been stable in the last couple of years in the Czech Republic, worldwide rises though. A ratio of incidence and mortality is considerable in bladder cancer since it is highest out of all genitourinary malignancies. An early diagnosis and adequate treatment is therefor determinig for its prognosis. There are several commercialy available urine tests, none of them is recommended as a standard diagnostic tool in any indication though. Urine cytology, as a complement of invasive cystoscopy, remains the only widely used method with all its limitations. Cell-free nucleic acids in urine (urine supernatant) belong amongs potential tumour biomarkers. Cell-free urinary DNA (ucfDNA) is excreted by cells undergoing necrosis or apoptosis although it can also originate from living cells. Their level in urine or serum can thus indicate a presence of malignancy. Micro RNA (miRNA) are short non-coding sequences of RNA produced outside of nucleus. They bind to complementary sequences of mRNA thus affecting its translation and protein formation. As such they play an important role in cell division and cancerogenesis. In our study, we correlated levels of ucfDNA in controls and patients with urothelial carcinoma of different...
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Activity of the cathepsin B in patient with the bladder cancer
Dušek, Pavel ; Babjuk, Marek (advisor) ; Soukup, Viktor (referee) ; Broďák, Miloš (referee)
Bladder cancer is the most common malignant neoplasm of the urogenital tract. Of non- invasive diagnostic methods in clinical practice normally only is used cytology to its limits. While there are several commercially available tests that have the character of a tumor marker. None of them, however, has not yet been recommended for the standard diagnosis or monitoring of patients with bladder cancer. Cathepsin B is a thiol - dependent protease found in normal circumstances in the lysosomes of mammalian cells. Cathepsin B are lysosomes involved in the degradation of proteins and has various functions in maintaining cell metabolism in normal conditions. The incidence of cathepsin B or its proteins and their high activity is described in a number of neoplastic diseases. About its importance for urological tumors has so far been only very few reports. Activity of the cathepsin B in patients with invasive bladder cancer were examined by determining its expression in tumor tissue and determining the concentrations of cathepsin B and pro-cathepsin B in their serum urine. Our results confirm that the diagnostic efficiency of the pro-cathepsin B urine urine is high. All so far published studies are focused on the investigation of biologically active proteins. Pro- cathepsin B is the biologically inactive...
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Interactions of muscarinic receptors and choline esterases: Functional examinations of esterase inhibitors in the rat.
Killi, Kumar Uday ; Wsól, Vladimír (advisor) ; Broďák, Miloš (referee) ; Delbro, Dick (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Uday Kumar Killi, M.Sc Supervisor: Prof. Ing. Vladimír Wsól, Ph.D. Co- Supervisor: Prof. Gunnar Tobin, D.D.S., Ph.D. Title of Doctoral Thesis: Interactions of muscarinic receptors and choline esterases: Functional examinations of esterase inhibitors in the rat. The parasympathetic nervous system regulates a number of vital body functions. The neurotransmission within the parasympathetic nervous system is exerted by acetylcholine, a phylogenetic old neurotransmitter, which acts on nicotinic and muscarinic receptors. Whilst the nicotinic receptors are located in the ganglia, the muscarinic receptors are located on the glands and smooth muscles. The muscarinic receptors belong to the large group of G glycoprotein- coupled receptors. Five subtypes exist of the muscarinic receptor (M1-M5), which can be either excitatory or inhibitory depending on subtype. Within the synaptic cleft, acetylcholinesterase hydrolyses acetylcholine and the inhibition of acetylcholinesterase, by for instance pesticides, causes accumulation of acetylcholine at the synaptic cleft, which in turn causes overstimulation of cholinoceptors. Muscarinic receptors and the acetylcholinesterase are important therapeutic...
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Impact of Warm Ischemia on Renal Function - Clinical Model of Tumor Resection of Solitary Kidney
Stránský, Petr ; Hora, Milan (advisor) ; Broďák, Miloš (referee) ; Doležel, Jan (referee)
Objective: The aim of this work is to evaluate the effect of warm ischemia on renal function. Methods: Within a multicentric study, the data about tumor-affected solitary kidney were obtained from 9 urological centers in the Czech Republic. Patients were divided into groups according to the WIT (warm ischemia time). In each group the mean preoperative serum creatinine was determined, as well as on 3rd and 7th postoperative day and the lowest GF postoperatively. In each group the mean R.E.N.A.L. nephrometric score was determined. Results: The study compriese data totally of 97 patients. The open approach was chosen in 78 cases, in 16 cases laparoscopic approach was chosen. The robotic surgery was performed in 3 patients. PN with zero ischemia was performed in 29 patients (30%). Conclusion: Our findings confirm that non-clamping partial nephrectomy in a solitary kidney minimizes renal injury. For the non-clamping partial nephrectomy can be mainly indicated smaller exophyticall tumors without deep parenchymal invasion. Unfortunately, most of PN should be performed with vascular clamping, allowing precise closure of collecting system, vascular and parenchymal defect, especially for larger tumors with deep parenchymal invasion. According to our observation that WIT of 15 minutes for a kidney is safe. Clamping of...
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