GATA-2 deficiency was recently described as common cause of overlapping syndromes of immunodeficiency, lymphedema, familiar myelodysplastic syndrome or acute myeloid leukemia. The aim of our study ...was to analyze bone marrow and peripheral blood samples of children with myelodysplastic syndrome or aplastic anemia to define prevalence of the GATA2 mutation and to assess whether mutations in GATA-2 transcription factor exhibit specific immunophenotypic features. The prevalence of a GATA2 mutation in a consecutively diagnosed cohort of children was 14% in advanced forms of myelodysplastic syndrome (refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and myelodysplasia-related acute myeloid leukemia), 17% in refractory cytopenia of childhood, and 0% in aplastic anemia. In GATA-2-deficient cases, we found the most profound B-cell lymphopenia, including its progenitors in blood and bone marrow, which correlated with significantly diminished intronRSS-Kde recombination excision circles in comparison to other myelodysplastic syndrome/aplastic anemia cases. The other typical features of GATA-2 deficiency (monocytopenia and natural killer cell lymphopenia) were less discriminative. In conclusion, we suggest screening for GATA2 mutations in pediatric myelodysplastic syndrome, preferentially in patients with impaired B-cell homeostasis in bone marrow and peripheral blood (low number of progenitors, intronRSS-Kde recombination excision circles and naïve cells).
Thiamine‐responsive megaloblastic anemia (TRMA) is a rare autosomal recessive disorder caused by mutations in the SLC19A2 gene. To date at least 43 mutations have been reported for the gene encoding ...a plasma membrane thiamine transporter protein (THTR‐1). TRMA has been reported in less than 80 cases worldwide. Here, we illustrate 2 female patients with TRMA first diagnosed in the Czech Republic and in central Europe being confirmed by sequencing of the THTR‐1 gene SLC19A2. Both subjects are compound heterozygotes with 3 different mutations in the SLC19A2 gene. In case 2, the SLC19A2 intron 1 mutation c.204+2T>G has never been reported before. TRMA subjects are at risk of diabetic ketoacidosis during intercurrent disease and arrythmias. Thiamine supplementation has prevented hematological disorders over a few years in both pediatric subjects, and improved glycaemic control of diabetes mellitus. Patient 1 was suffering from hearing loss and rod‐cone dystrophy at the time of diagnosis, however, she was unresponsive to thiamine substitution. Our patient 2 developed the hearing loss despite the early thiamine substitution, however no visual disorder had developed. The novel mutation described here extends the list of SLC19A2 mutations causing TRMA.
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Background: The prevalence of autoimmune thyroiditis (AIT), as the most common autoimmune disease (AD) and papillary thyroid cancer (PTC) is steadily rising in children. The aim of this study was to ...determine the coexistence of other AD and thyroid carcinoma (TC) in AIT. Methods: The cross-sectional study conducted at a tertiary center comprised AIT children (< 19 years). Data on age/sex, thyroid function and ultrasound, autoantibodies, associated AD, familial occurence of AD and the occurence of TC for each child were collected. Results: In total, 231 eligible patients (77% females) were included. The most common onset (66%) was during adolescence. At onset, hypothyroidism was detected in 59.3%; hashitoxicosis in 1.3%. The positivity of both autoantibodies was present in 60.6%, the negativity was in 3,5%. We confirmed a high frequency (44.6%) of AD with AIT predominance in parents and/or grandparents of patients and in siblings (7.4%). 15.2% had at least 1 comorbid AD, of which type 1 diabetes mellitus was the most common (8.5%). Over a period of 7 years TC was diagnosed in 16 patients (mean age 13.5 years) with predominance of PTC in 15 (94%) patients. AIT had concurrently 69% patients. 56% of patients had metastases (89% in AIT subjects). An invasive PTC was present in 44% (86% in AIT subjects). Conclusions: The prevalence rate of AD in AIT and first-degree relatives is high, and several new associations have been reported. Providers should be aware of comorbidities and TC in AIT as this would help in early diagnoses and timely interventions.
Most minimal residual disease-directed treatment interventions in current treatment protocols for acute lymphoblastic leukemia are based on bone marrow testing, which is a consequence of previous ...studies showing the superiority of bone marrow over peripheral blood as an investigational material. Those studies typically did not explore the prognostic impact of peripheral blood involvement and lacked samples from very early time points of induction.
In this study, we employed real-time quantitative polymerase chain reaction analysis to examine minimal residual disease in 398 pairs of blood and bone marrow follow-up samples taken from 95 children with B-cell precursor acute lymphoblastic leukemia treated with the ALL IC-BFM 2002 protocol.
We confirmed the previously published poor correlation between minimal residual disease in blood and marrow at early treatment time points, with levels in bone marrow being higher than in blood in most samples (median 7.9-fold, range 0.04-8,293-fold). A greater involvement of peripheral blood at diagnosis was associated with a higher white blood cell count at diagnosis (P=0.003) and with enlargement of the spleen (P=0.0004) and liver (P=0.05). At day 15, a level of minimal residual disease in blood lower than 10(-4) was associated with an excellent 5-year relapse-free survival in 78 investigated patients (100% versus 69 ± 7%; P=0.0003). Subgroups defined by the level of minimal residual disease in blood at day 15 (high-risk: ≥ 10(-2), intermediate-risk: <10(-2) and ≥ 10(-4), standard-risk: <10(-4)) partially correlated with bone marrow-based stratification described previously, but the risk groups did not match completely. No other time point analyses were predictive of outcome in peripheral blood, except for a weak association at day 8.
Minimal residual disease in peripheral blood at day 15 identified a large group of patients with an excellent prognosis and added prognostic information to the risk stratification based on minimal residual disease at day 33 and week 12.
This diploma thesis is focused on the verification of the theory application coming from the conclusions of Stanislav Balíks thesis, which generalizes election behaviour during elections for local ...authority and it is based on an analysis of election facts in the regions of Šumperk and Jeseník. The aim of the thesis is to verify whether the theory conclusions are applicable to the results interpretation of election behaviour and the characteristics of the party system in other regions of the Czech Republic. The thesis is divided into two parts, theoretical and practical. In the theoretical part there is worked on the theoretical and legislative conclusions and Stanislav Balíks thesis. The thesis itself starts with the basic characteristics of the region of Klatovy, its administrative and demographic structuring. The core of the thesis is the data analysis of the Czech Statistical office, concerning the elections from 1994 to 2014. The attention is paid on voter turnout at municipality elections depending on different factors and the results of the elections are discussed in detail from the point of view of the suggesting parties and the number of women in municipality politics. The last chapters include a summary of the data from the region of Klatovy, it is compared with the results of Stanislav Balíks thesis and the application of his theory in another region in the Czech Republic is discussed.
This thesis deals with the question of the concept of freedom in the Gospel of John and the relationship between freedom and truth. The first part of this thesis is focused on the research of ...concepts of freedom and truth from the Old Testament to the New Testament, it is a description of historical background in which both terms were formed and transformed. This thesis also includes a detailed exegesis of the text of J 8.31-36, which served as the starting point. Due the fact that notion of freedom is most often found in the New Testament in the Gospel of John and Paul's Epistles, I insert a chapter charting the occurrence and use of the concept of freedom in Paul's epistles. In the main part of the thesis I compare the use of the concept of freedom in the Gospel of John and in Paul's letters.
Background: Thymidine kinase (TK) is involved in nucleic acid synthesis and is therefore considered to be an important proliferation
tumor marker. Our main goal was to determine the significance of ...elevated TK levels as a relapse marker during follow-up with
child patients suffering from acute leukemia. Patients and Methods: TK serum levels in 38 children with acute leukemia (34
lymphoblastic, 4 myeloblastic) were determined using radio-receptor analysis (RRA, Immunotech, Prague, USA). All patients
included in this study had had TK examined before the start of the treatment and at least twice during the follow-up. Results:
Our results showed that TK serum levels at the time of diagnosis were extremely high (78-5826 U/l, median value 403 U/l, normal
<8 U/l), while in remission TK serum levels were much lower (5-80 U/l, median value 31 U/l). During relapse of acute leukemia
(5 cases), TK levels increased considerably to measurements between 120-800 U/l (median value 324 U/l). The study showed that
the elevation of TK serum levels during follow-up was a helpful marker for the recognition of an early stage of relapse and
in some cases occurred as early as one month before the appearance of clinical signs. Sensitivity in this case was 87% and
thus TK serum levels seem to be a very good parameter during follow-up because of acceptable sensitivity, low cost (4 $/sample)
and the elimination of a requirement for screening of bone marrow samples. Conclusion: While TK serum levels were helpful
in predicting relapse during follow-up, it is necessary to note that they did not correlate with prognosis in our group of
patients during the time of the initial diagnosis of acute leukemia.
Thiamine-responsive megaloblastic anemia (TRMA) is a rare autosomal recessive disorder caused by mutations in the SLC19A2 gene. To date at least 43 mutations have been reported for the gene encoding ...a plasma membrane thiamine transporter protein (THTR-1). TRMA has been reported in less than 80 cases worldwide. Here, we illustrate 2 female patients with TRMA first diagnosed in the Czech Republic and in central Europe being confirmed by sequencing of the THTR-1 gene SLC19A2. Both subjects are compound heterozygotes with 3 different mutations in the SLC19A2 gene. In case 2, the SLC19A2 intron 1 mutation c.204+2T>G has never been reported before. TRMA subjects are at risk of diabetic ketoacidosis during intercurrent disease and arrythmias. Thiamine supplementation has prevented hematological disorders over a few years in both pediatric subjects, and improved glycaemic control of diabetes mellitus. Patient 1 was suffering from hearing loss and rod-cone dystrophy at the time of diagnosis, however, she was unresponsive to thiamine substitution. Our patient 2 developed the hearing loss despite the early thiamine substitution, however no visual disorder had developed. The novel mutation described here extends the list of SLC19A2 mutations causing TRMA.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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