AIM OF THE STUDY: To establish endothelial activation markers which could uncover endothelial damage during hysiological pregnancy and pregnacies with chronic hypertension. SETTINGS: Department of Hemato-oncology, Obstetrics and Gynecology and Department of Medical Genetics and Fetal Medicine Medical Faculty of Palacký University Olomouc, Department of Obstetrics and Gynecology Medical Faculty Ostrava. METHODS: We examined 298 pregnant women with a physiological pregnancy. Venous blood samples were collected from the women in both arms at the beginning of the pregnancy, a second sample was collected in the interval 24-28 weeks gestation, the third sample was colected about the 36 weeks of gestation. Parameters were examined using methods: t-PA - ELISA, PAI-1 - ELISA, vWF - EIA, ePCR - ELISA, MMP-2,9 - ELISA with fluorogenic detection, TIMP-2 - ELISA, endothelial microparticles - flow cytometry. RESULTS: In accordance with the literature, we have observed in our study significantly increased endothelial activatition in hypertensive pregnancies compared with women with physiological pregnancy, as evidenced by significant increases in vWF activity and antigen, thrombomodulin and PAI-1 in all trimesters. In the other investigated parameters statistically significant changes were not observed. CONCLUSION: We have found significant signs of endothelial dysfunction in the group of women with pre-existing hypertension, a wide range of parameters examined markers indicating an significantly increased endothelial activation pregnant women with pre-existing hypertension, confirming the need for strict follow-up of pregnant women with hypertensive disease.
- MeSH
- cévní endotel patofyziologie MeSH
- chronická nemoc MeSH
- hypertenze komplikace epidemiologie MeSH
- kardiovaskulární komplikace v těhotenství epidemiologie MeSH
- kohortové studie MeSH
- lidé MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika epidemiologie MeSH
UNLABELLED: Bleeding disorders in pregnancy represent heterogenous and often serious group of diseases. Solving of this problems and proper treatment of the patiens requires close cooperation between obstetricians and hematologists. There are disorders specific for pregnancy (HELLP syndrom) and disorders occurring independently in pregnancy, but these can be modified in pregnancy as well. Bleeding and postpartum haemorrhage still remain the leading cause of maternal mortality. KEYWORDS: bleeding - pregnancy - thrombocytopenia - coagulopathy.
AIM OF THE STUDY: To establish endothelial activation markers which could uncover endothelial damage during physiological pregnancy. TYPE OF STUDY: Prospective study. METHOD: We examined 403 pregnant women with a physiological pregnancy. Venous blood samples were collected from the women at the beginning of the pregnancy, a second sample was collected in the interval 24-28 weeks gestation. Parameters were examined using methods: t-PA--ELISA, PAI-1--ELISA, vWF Ag--EIA ePCR--ELISA, MMP-2,9--ELISA with fluorogenic detection, TIMP-2--ELISA, endothelial microparticles - flow cytometry. RESULTS: The level of vWF antigen increased during the entire course of pregnancy (in the I. trimester the average level was 152.32%, in the II. and III. trimester 173.34% and 216.20% respectively). At the same time, vWf activity also increased (I. trimester average level 130.20%, II. and III. trimester 150.09% and 181.91% respectively). The level of thrombomodulin significantly increased during pregnancy (I. trimester average level 19.05 ng/ml, II. and III. trimester 28.47 ng/ml and 39.86 ng/ml respectively). The level of soluble form of EPCR increased during pregnancy (I. trimester average level 201.76 ng/ml, II. and III. trimester 274.68 ng/ml and 324.07 ng/ml respectively). The level of PAI-1 increased during the entire course of pregnancy (I. trimester average level 36.14 ng/ml, II. and III. trimester 50.07 ng/ml and 60.12 ng/ml respectively). The level of t- PA did not change significantly during the course of pregnancy (I. trimester average level 2.48 ng/ml, II. and III. trimester 2.97 and 3.34 ng/ml respectively). The levels of MMP-2 (I. trimester average level 9043.76 RFU, II. and III. trimester 9315.38 and 8800.27 RFU respectively), MMP-9 (I. trimester average level 8371.90, II. and III. trimester 8290.81 and 7470.50 respectively), TIMP-2 (I. trimester average level 92.5 ng/ml, II. and III. trimester 98.5 and 96.5 ng/ml respectively) or endothelial microparticles (I. trimester average level 3838.38 particles/microl, II. and III. trimester 3836.59 and 3650.59 particles/microl respectively) did not change significantly throughout the individual trimesters. CONCLUSION: We confirmed the hypothesis regarding the significant influence pregnancy has on changes in levels of these markers.
- MeSH
- biologické markery krev MeSH
- CD antigeny krev MeSH
- cévní endotel fyziologie MeSH
- endoteliální receptor proteinu C MeSH
- inhibitor aktivátoru plazminogenu 1 krev MeSH
- lidé MeSH
- matrixové metaloproteinasy krev MeSH
- receptory buněčného povrchu krev MeSH
- těhotenství krev MeSH
- tkáňový aktivátor plazminogenu krev MeSH
- tkáňový inhibitor metaloproteinasy 2 krev MeSH
- trimestry těhotenství MeSH
- trombomodulin krev MeSH
- von Willebrandův faktor analýza MeSH
- Check Tag
- lidé MeSH
- těhotenství krev MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biologické markery MeSH
- CD antigeny MeSH
- endoteliální receptor proteinu C MeSH
- inhibitor aktivátoru plazminogenu 1 MeSH
- matrixové metaloproteinasy MeSH
- PROCR protein, human MeSH Prohlížeč
- receptory buněčného povrchu MeSH
- tkáňový aktivátor plazminogenu MeSH
- tkáňový inhibitor metaloproteinasy 2 MeSH
- trombomodulin MeSH
- von Willebrandův faktor MeSH
OBJECTIVE: Summary of the current knowledge of the role of endotelial activation markers in the pathogenesis of the selected diseases and high-risk pregnancy. DESIGN: Review article. METHODS: Compilation of the published data from scientific literature. CONCLUSIONS: The endothelium functions in a multitude of physiological processes including the control of cellular trafficking, the regulation of vasomotor tone and maintenance of blood fluidity. Preeclampsia is compared by the the insufficient trofoblastic invasion to the maternal spiral arteries. This changes lead to the insufficiency of the fetoplacental blood flow. The ischaemia of the fetoplacental unit cause the release of specific factors into maternal vessels and subsequent activation of the endothelium and vasoconstriction. We present a short summary of the clinically important endothelial markers and current possibilities of laboratory testing.
- MeSH
- biologické markery analýza MeSH
- cévní endotel fyziologie patofyziologie MeSH
- inhibitor aktivátoru plazminogenu 1 analýza MeSH
- komplikace těhotenství patofyziologie MeSH
- lidé MeSH
- těhotenství MeSH
- tkáňový aktivátor plazminogenu analýza MeSH
- trombomodulin analýza MeSH
- von Willebrandův faktor analýza MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- biologické markery MeSH
- inhibitor aktivátoru plazminogenu 1 MeSH
- tkáňový aktivátor plazminogenu MeSH
- trombomodulin MeSH
- von Willebrandův faktor MeSH
Chromosomal aberrations are one of the most important prognostic factors in patients with acute myeloid leukemia (AML). This work present analysis of conventional cytogenetic results completed by fluorescence in situ hybridization (FISH) obtained from 105 patients in the time of diagnosis of AML. The median age of patients was 51 years (range 19-79 years), with slight predominance of women (female to male ratio 1.2:1). The evaluated group involved all patients with AML diagnosis, treated by intensive induction chemotherapy in the Department of Hematology-oncology, University Hospital, Olomouc during last 4 years with assessable cytogenetic results. Chromosomal changes were found in 63 (60%) patients. The most often affected chromosomes in succession of frequency were 8, 17, 7, 5, 11, 15, 16 a 21. Based on found specific and frequent chromosomal changes the patients were divided into 3 prognostic subgroups and the significance of chromosomal aberrations was evaluated. The subgroup of 17 patients with good prognosis consisted of a patients with acute promyelocytic leukemia with translocation t(15;17), 4 patients with t(8;21) and 4 patients with inv(16). 14 patients of 17 live in complete remission, median of overall survival (OS) is 63 weeks. The subgroup of intermediate prognosis was formed by 60 patients, 42 had normal karyotype and 18 patients had other chromosomal abnormalities. Median OS of this group was 35 weeks. The third subgroup with poor prognosis consisted of 28 patients with changes of chromosomes 3, 5, 7, 11 and complex karyotype. 64.3% of patients received complete remission and median OS was 35 weeks. Statistical evaluation of OS showed significant difference (p = 0.002) in subgroup with good prognosis versus subgroup with poor prognosis and in subgroup with good prognosis versus subgroup with intermediate prognosis (p = 0.014). Statistical significance of OS in subgroup with intermediate prognosis versus subgroup with poor prognosis was not proved (p = 0.34), but fit appeared in evaluation of both groups in patients under 55 years. It seems that in patients in age 55 and more the age is independent poor prognostic factor and findings of chromosomal aberrations do not significantly influence prognosis.
- MeSH
- akutní nemoc MeSH
- chromozomální aberace * MeSH
- cytogenetické vyšetření MeSH
- dospělí MeSH
- hybridizace in situ fluorescenční MeSH
- indukce remise MeSH
- lidé středního věku MeSH
- lidé MeSH
- míra přežití MeSH
- myeloidní leukemie farmakoterapie genetika mortalita MeSH
- prognóza MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- práce podpořená grantem MeSH
The presented study compares the efficacy and the toxicity of idarubicine and mitoxantrone in combination with cytosar (3 + 7) in induction treatment of the patients with AML aged 55-75. 31 patients at the age of 55-75 (median 62) were evaluated in the arm with idarubicine and 29 patients at the age of 57-74 (median 64) in the arm with mithoxantrone. Complete haematological remission was achieved in 13 patients (41.9%) in the arm with idarubicine and 15 patients (51.7%) in the arm with mitoxantrone. The medians of overall survival time (OS) and disease free survival time (DFS) were 22 and 44 weeks in the idarubicine arm and 35 and 40 weeks in the mitoxantrone arm, respectively. Statistical analysis did not prove any significant difference in the complete remission rates, in the number of deaths during cytopenia, in the OS or DFS, in the duration of hospitalisation, severe neutropenia and thrombopenia, in the number of days with febrile neutropenia, or in the consumption of platelets and erythrocytes transfusion units between both arms. Despite the fact that these results are not statistically significant in favour of any treatment arm, which is probably influenced also by the small number of evaluated patients, more favourable results were achieved in the arm with mithoxantrone with the respect to the evaluated parameters. From the point of view of cost-effectiveness, the difference could be observed when considering the price of both intercalating cytostatics. The use of mitoxantrone (Refador, Lachema) is 15x times cheaper per course of treatment than the use of idarubicine (Zavedos, Pharmacia). Autologous peripheral blood stem cells transplantation (APBSC) was carried out only in 4 patients younger than 60. No one of them was cured by APBSC but the median of OS of these patients was longer than the median in the other patients of the group. The results achieved are comparable with those of other trials conducted by various foreign groups. The possible causes of our unfavourable treatment results in this high-risk category of aged patients and the ways how to individualize the treatment with the use of prognostic factors analysis and how to improve the quality of life of the patients has been discussed.
- MeSH
- akutní nemoc MeSH
- cytarabin aplikace a dávkování MeSH
- idarubicin škodlivé účinky terapeutické užití MeSH
- indukce remise MeSH
- lidé středního věku MeSH
- lidé MeSH
- míra přežití MeSH
- mitoxantron škodlivé účinky terapeutické užití MeSH
- myeloidní leukemie farmakoterapie mortalita MeSH
- prospektivní studie MeSH
- protinádorové látky terapeutické užití MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- klinické zkoušky MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- srovnávací studie MeSH
- Názvy látek
- cytarabin MeSH
- idarubicin MeSH
- mitoxantron MeSH
- protinádorové látky MeSH
The authors describe a newly identified beta0-thalassaemic mutation found in two subjects from two generations of a Slovak family. The beta0-thalassaemic allele developed by insertion of one nucleotide (+G, CD 7/8) into the first exon of the beta-globin gene. The mutation causes a shift of the open globin reading frame which leads to the development of a terminal codon in codon 22. The thalassaemic allele is associated with the mediterranean haplotype IX. The mutation has in both heterozygotes the phenotype of beta0-thalassaemia minor with a slightly elevated level of HbF.
- MeSH
- alely MeSH
- beta-talasemie genetika MeSH
- exony genetika MeSH
- fenotyp MeSH
- globiny genetika MeSH
- haplotypy MeSH
- heterozygot MeSH
- lidé středního věku MeSH
- lidé MeSH
- posunová mutace * MeSH
- rodokmen MeSH
- sekvenční analýza DNA MeSH
- terminační kodon genetika MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
- Názvy látek
- globiny MeSH
- terminační kodon MeSH
In 29 Czech and Slovak families with the most frequent and newly identified beta-thalassaemic alleles and with some structural haemoglobin variants (Hb E, Hb Haná, Hb Santa Ana) haplotypes of the beta-globin locus of alleles with these mutations were identified. In most instances haplotypes I and V were involved which were found in 57% of the patients. The bond of the most common beta-thalassaemic mutation: IVS-I-1, IVS-I-110, CD 39 (C-T), IVS-II-745, IVS-I-6 with alleles with the same haplotypes as in the mediterranean region suggests a mediterranean origin of these mutations. In Hb Santa Ana a hitherto not described haplotype was identified (-(+)-(-)-(+3), indicating a de novo origin of the mutation. Also in newly identified beta-thalassaemic mutations in CD 7/8 (+G), in CD 38/39 (-C) and in HbE and Hb Haná de novo development is probable.
- MeSH
- beta-talasemie genetika MeSH
- globiny genetika MeSH
- haplotypy * MeSH
- hemoglobiny abnormální analýza genetika MeSH
- lidé MeSH
- polymerázová řetězová reakce MeSH
- polymorfismus délky restrikčních fragmentů MeSH
- polymorfismus genetický MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
- Slovenská republika MeSH
- Názvy látek
- globiny MeSH
- hemoglobiny abnormální MeSH
The paper demonstrates the importance of sequence analysis of DNA for the identification of Hb-Sydney [alpha2-beta2 67 (E11) Val-Ala]. The latter was considered erroneously, based on results of biochemical analyses to be Hb-M-Milwaukee [alpha2 beta2 67 (E 11) Val-Glu]. With the unstable Hb-Sydney correspond also phenotypical manifestations of disease (haemolytic anaemia with Heinz bodies in red blood cells). Sequence analysis of DNA of patients with Hb-Olomouc [alpha 2 beta 2 (F 2) Ala-Asp] revealed that mutation of Ala-Asp in position 86 (F 2) of the beta globin chain is coded by mutation C-->A (GCC-GAC).
- MeSH
- chybná diagnóza MeSH
- hemoglobinopatie diagnóza genetika MeSH
- hemoglobiny abnormální genetika MeSH
- lidé MeSH
- sekvenční analýza DNA MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
- Názvy látek
- hemoglobin Olomouc MeSH Prohlížeč
- hemoglobiny abnormální MeSH
The authors describe the identification and the clinical manifestations of a new structural variant of haemoglobin found in three subjects from two generations of a Moravian family. It is manifested by mild haemolytic anaemia with Heinz bodies in the proband and a slightly elevated value of methaemoglobin. The sequential analysis of the beta-globin gene provided evidence that the cause is mutation CAT-AAT in codon 63 which leads to the exchange of distal histidine /E7/ for asparagine. The ratio of beta X:beta A is 38:62. The mother with the same mutation is asymptomatic. The relative amount of beta X:beta A mRNA transcripts in mother and daughter are equal. This indicates that the clinical differences are not due to a different gene expression. The mother is a heavy smoker with an elevated CO-Hb level that probably protect the mutant against oxidative denaturation and increases thus the stability of Hb-Haná. The authors discuss also the finding of two abnormal stripes assessed by three electrophoretic methods.
- MeSH
- bodová mutace MeSH
- dítě MeSH
- exprese genu * MeSH
- globiny genetika MeSH
- hemoglobiny abnormální genetika MeSH
- kojenec MeSH
- kongenitální hemolytická anemie genetika MeSH
- kouření genetika MeSH
- lidé MeSH
- methemoglobinemie genetika MeSH
- rodokmen MeSH
- sekvenční analýza DNA MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
- Názvy látek
- globiny MeSH
- hemoglobiny abnormální MeSH
