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Impact of glucocorticoid treatment on musculosceletal system of pediatric patients with acute lymphoblastic leukemia.
Petráčková, Karolína ; Jevič, Filip (advisor) ; Šrámková, Lucie (referee)
This bachelor thesis aims to provide a general overview of complications of musculoskeletal system in pediatric patients diagnosed with acute lymphoblastic leukemia (ALL) undergoing chemotherapy treatment involving high cumulative doses of glucocorticoids. Musculoskeletal complications include steroid myopathy, osteonecrosis and reduced bone mineral density. The first part describes their basic pathophysiological mechanisms and the risk factors of their origin. The second part presents the current possibilities of muscle strength assessment and available exercise programs. Furthermore, diagnosis of osteonecrosis and bone mineral density are presented together with current possibilities of therapeutic intervention. The thesis also covers characteristics of muscle strength measuring methods and exercise programs along with presentation of the results of individual studies. In the discussion part, there are broken down the limits, advantages and disadvantages of using the muscle strength measuring methods and exercise programs in clinical practice.
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The Influence of Motivational Elements in Paediatric Physiotherapy Focused on the Patients with Acute Lymphoblastic Leukemia - Pilot Study
Chytrá, Markéta ; Jevič, Filip (advisor) ; Králová, Aneta (referee)
THE INFLUENCE OF MOTIVATIONAL ELEMENTS IN PAEDIATRIC PHYSIOTHERAPY FOCUSED ON THE PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA - PILOT STUDY Abstract The efficacy of acute lymphoblastic leukemia (ALL) treatment in childhood is still increasing and the quality of life of these children is starting to be the focus of interest. The physiotherapy affects in preventive and reactive way the late effects of treatment which may reduce the quality of life. An insufficient motivation of children can be a reason of a reduced adherence to a physiotherapeutic intervention. The goal of this study was to ascertain the influence of the motivational elements in the paediatric physiotherapy in the improvement of motor functions, the quality of life, the motivation to the exercise and the frequency of exercise. There were 9 patients diagnosed with ALL in the maintenance phase of treatment (average age 7,3 years, age range 5,2 - 10,1, 5 girls and 4 boys). All probands underwent a 6- weeks-excercise programme that contains the exercise from the DNS method, yoga for children and stretching. The assessment was performed by Bruninks-Oseretsky Test (BOT2), 6 minute walking test (6MWT), goniometric measurement of ankle joint dorsiflexion, Pediatric Quality of Life Inventory (PedsQL), Intrinsic Motivation Inventory (IMI) and the...
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Lineage plasticity in normal and malignant lymphocyte precursors
Rezková Řezníčková, Leona
The classical scheme of hematopoiesis presumes early separation of lymphoid and myeloid precursors. Recently, more complex models are put forward, suggesting greater flexibility of hematopoiesis with progenitors sharing lymphoid and myeloid potential. Acute hybrid leukemia is a malignancy, in which it is not possible to assess unambiguously myeloid or lymphoid lineage of origin. The behaviour of those malignancies favors new models of hematopoiesis. Our work concentrated mainly on the research of childhood leukemias with lineage switch from lymphoid to myeloid lineage during induction treatment. Our task within this extensive project was to determine lineage assignment of leukemic blasts using detection of immunoglobulin and T-cell receptor gene rearrangements. We confirmed that myeloid cells derived during the treatment in all patients descend from the original lymphoid clone. We also investigated the expression of selected genes in those cases compared to common leukemia types. Lastly, we explored prognostic impact of TCR rearrangements (and thus lymphoid lineage commitment) in T-lineage leukemia.
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Heteroploidy in bone marrow cells of children with acute lymphoblastic leukemia (ALL)
Matějčková, Nicole ; Zemanová, Zuzana (advisor) ; Krylov, Vladimír (referee)
Acute lymphoblastic leukemia is the most common type of cancer in children. It is a very heterogenous disease in which many recurrent chromosomal abnormalities have been described. The most important chromosomal abnormalities associated with a good prognosis are t(12;21)(p13;q22) which result in ETV6/RUNX1 fusion and hyperdiploidy. On the contrary findings suggesting a poor prognosis are t(9;22)(q34;q11) leading to fusion gene BCR/ABL1, MLL rearrangements or hypodiploidy. Heteroploidy is one of the most frequent findings in childhood ALL. It is characterised by nonrandom gain or loss of chromosomes from diploid cells. One of the most important findings in childhood ALL is hyperdiploidy where a non-random gain of chromosomes is present. Hyperdiploidy has a favorable prognosis and the impact of additional structural aberations requires further research. Another prognostically important group of heteroploidy is hypodiploidy. It is a quite rare finding and has a very poor outcome. There are non-random acquired chromosome losses observed in hypodiploid cells. Hypodiploid cell line may be masked with a doubled hyperdiploid clone which makes it difficult to identify. Proper and early cytogenetical analysis of heteroploid cells is very important as it contributes assigning correct diagnosis and risk stratification,...
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Leukaemias with BCR/ABL fusion gene.
Hovorková, Lenka ; Zuna, Jan (advisor) ; Zemanová, Karla (referee)
Philadelphia (Ph) chromosome, as a result of reciprocal translocation, is in majority of cases connected to two types of leukaemia - chronic myelogenous (CML) and acute lymphoblastic (ALL). The translocation occurs within large intronic sequences of BCR and ABL genes. The breakpoints are specific for individual patient and may be used as a target for monitoring of leukemic burden (MRD, minimal residual disease) during the treatment. In general, MRD is an important prognostic factor, which influences the treatment intensity. Two standardized methods are currently used for its monitoring. The first one is based on the detection of clonal specific Immunoglobulin and/or T-cell receptor genes rearrangements (and thus cannot be used for CML cases) at the DNA level, the second one utilizes detection of the BCR/ABL fusion gene at the mRNA level. Our aim was to optimize and standardize the process to find individual patient breakpoints on Ph chromosome and to use it for MRD quantification. We found the breakpoint in 80 % cases. The MRD data from 15 patients obtained by our method were compared to the levels obtained by standard methods (Ig/TCR and BCR/ABL transcript quantification). In all but 1 patient we found significant discrepancies, raising the questions about leukemic origin and the most accurate method for...
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Elucidating the interactions of interleukin-1alpha with components of the eukaryotic transcription machinery
Zámostná, Blanka ; Pospíšek, Martin (advisor) ; Černý, Jan (referee) ; Mělková, Zora (referee)
4 ABSTRACT Interleukin-1α (IL-1α) is a pleiotropic cytokine and a key mediator of host immune response. It is synthesised as a 31-kDa precursor, that is cleaved by the cysteine protease calpain into the 17-kDa mature IL-1α and the 16-kDa N- terminal peptide of IL-1α (IL-1αNTP). Although IL-1α can be secreted, act on target cells through the surface receptor IL-1RI and trigger the signal transduction pathway, increasing evidence points toward the involvement of IL-1α in certain nuclear processes. IL-1αNTP is highly conserved among higher eukaryotes and contains a nuclear localisation sequence; indeed, both the precursor and IL-1αNTP are found in the cell nucleus. Previously, a genetic interaction of IL-1α with nuclear histone acetyltransferase (HAT) complexes has been reported from mammalian cells and, interestingly, also from the heterologous yeast model. This thesis extends the research of the nuclear function of IL-1α and demonstrates that IL-1α physically associates with the HAT/Core module of yeast SAGA and ADA HAT complexes. Results of the HAT subunit gene knock-out experiments followed by a set of co-immunoprecipitations also suggest a novel model of the yeast SAGA complex assembly, in which ADA appears to represent only a partly functional HAT complex. In its natural milieu of mammalian cells, IL-1α...
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The study of genetic changes of children patients suffering from the acute lymphoblastic leukemia (ALL) using mFISH / mBAND and micro-arrays.
Bártů, Linda ; Zemanová, Zuzana (advisor) ; Březinová, Jana (referee)
Acute lymphoblastic leukemia is the most common malignancy in children. The most important examination at the time of diagnosis includes karyotype of leukemic cells which divides patients into prognostic groups according to cytogenetic finding. In up to 90 % of patients the chromosomal aberrations with well known clinical significance are designated. One of cytogenetic type is high hyperdiploid ALL (51-68 chromosomes) associated with favorable prognosis. Nevertheless, relapses of the disease occur even in these children. One possible reason why this happens could be an increased genomic instability of leukemic cells that causes cryptic structural rearrangements. In a retrospective study, we examined a total of 232 children with newly diagnosed B-ALL using conventional cytogenetic analyses and interphase fluorescence in situ hybridization (I-FISH) with a panel of DNA probes (Abbott Vysis) in order to detect heteroploid cells. In patients with suspect cryptic structural chromosome aberrations, we analyzed the karyotypes in detail by multicolor FISH and multicolor banding (mFISH/mBAND; MetaSystems). The extent of aberrations was determined by comparative genomic hybridization on BAC arrays (array CGH; BlueGnome). Cell clones with high hyperdiploid karyotype were detected in a total of 102 children (44 %). In...
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Lineage plasticity in normal and malignant lymphocyte precursors
Rezková Řezníčková, Leona ; Froňková, Eva (advisor) ; Otáhal, Pavel (referee)
Klasické schéma vývoje hematopoetických buněk předpokládá časné oddělení lymfoidního a myeloidního prekurzoru. V poslední době jsou navrhovány složitější modely, které předpokládají větší flexibilitu hematopoezy a navrhují existenci progenitorů s lymfoidním i myeloidním potenciálem. Akutní hybridní leukémie jsou malignity, které podle různých kritérií nelze jednoznačně zařadit k lymfoidní nebo k myeloidní linii a jejichž chování spíše dává za pravdu novým modelům hematopoezy. Předkládaná práce se zabývala především výzkumem dětských leukémií s přesmykem z lymfoidní do myeloidní linie během indukční léčby. Jedná se o rozsáhlý projekt, v jehož rámci si diplomová práce si kladla za úkol určit liniové zařazení leukemických blastů pomocí detekce přestaveb genů pro imunoglobuliny a T-buněčné receptory (TCR). Potvrdili jsme, že myeloidní buňky derivované v průběhu léčby pochází u všech pacientů z původního lymfoidního klonu. Dále jsme u těchto případů zkoumali expresi vytipovaných genů ve srovnání s běžnými druhy leukémií. Třetí částí práce byl výzkum prognostického významu přítomnosti přestaveb TCR (a tedy příslušnosti k lymfoidní linii) u leukémií z T-lymfoidní řady.
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Myeloid lineage involvement in BCR/ABL-positive acute lymphoblastic leukaemia
Hovorková, Lenka ; Zuna, Jan (advisor) ; Mikyšková, Romana (referee)
The Philadelphia chromosome has been discovered in 1960. This chromosomal aberration was mistakenly associated only with chronic myeloid leukaemia (CML) for decade. However, this type of translocation including chromosomes 9 and 22 was found in patients with different type of neoplasia - acute lymphoblastic leukaemia (ALL). Different lineage involvement has been found in these two types of leukaemia. Whereas in Ph-positive ALL, the Philadelphia chromosome is restricted to the lymphoid lineage, in CML patients mostly myeloid cells are those being Ph-positive. Hence it seems quite trivial to distinguish between ALL and CML. But there is a phase of CML called lymphoid blast crisis which is indistinguishable from ALL. The possibility of distinguishing between CML in lymphoid blast crisis and ALL would inhere in determining myeloid lineage involvement. Actually it had been shown that some patients with Ph+ ALL have involved also a myeloid lineage. Different types of treating protocols are used in CML and ALL. In addition, prognoses for both types of leukaemia are different. Thus it is crucial to distinguish between this two disorders and revealing of any difference can impact the treatment outcome of above mentioned malignancies. Detection of minimal residual disease according to involvement of myeloid or CD34+...
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Continuous measurement of blood pressure
Kopčil, Petr ; Chmelař, Milan (referee) ; Nováková, Zuzana (advisor)
This paper deals with the physiology of cardiovascular system, explains elementary principles related to blood flow physiology and describes some basic mechanisms for regulation and blood pressure measurement. The paper also includes a description of the medical device, known as the Finometer (FMS, Netherlands), for continuous non-invasive blood pressure measurement and suggests a way to data export from this device to a text file. It introduces user friendly application to manage recorded data written in MATLAB. There is a statistical test to assess the difference between two statistical data files in the last chapter of this paper which includes a comparison our results with studies made in Czech Republic and other countries too.
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