Publications by authors named "Ondrej Soucek"

34 Publications

Multiple sclerosis and immune system biomarkers: Novel comparison in glatiramer acetate and interferon beta-1a-treated patient groups.

Mult Scler Relat Disord 2021 Jun 15;53:103082. Epub 2021 Jun 15.

Department of Neurology, Masaryk University, Faculty of Medicine and University Brno, Brno, Czech Republic.

Background: Multiple sclerosis (MS) is a chronic, demyelinating disease of the central nervous system (CNS). T cells and B lymphocytes are involved in the development of this disease.

Methods: The following biomarkers were determined in peripheral blood in 28 patients treated with glatiramer acetate (GA) and 21 patients treated with interferon beta 1-a (IFN): IL-10, BAFF, Mx1, IgG, IgG1, IgG2, IgG3 and IgG4 (at baseline and after 6 months of treatment). All participants had confirmed MS diagnosis.

Objectives: The primary objective is to assess a percentual change of biomarkers after 6 months since the first-line treatment initiation with GA or IFN. The secondary objective is to explore correlations between the baseline biomarkers' values (levels).

Results: A positive trend was observed in the increase in IL-10 concentration by 30.33 % (IFN) and by 15.65 % (GA). In the IFN group, we observed a statistically significant increase in the BAFF protein concentration by 29.9% (P < 0.001). We found that Mx1 protein levels did not change with the administration of GA, which can be explained by the different mechanisms of action of GA. The serum levels of IgG immunoglobulins and both IgG1 and IgG4 subclasses in both groups of patients were increased. Thus, our data were in accordance with the generally accepted assumption that both IFN and GA are capable of modulating the B cell system.

Conclusions: Our results suggest that treatment with IFN and GA has a more pronounced influence on the B cell system of MS.
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http://dx.doi.org/10.1016/j.msard.2021.103082DOI Listing
June 2021

Novel presentation of the c.1856A > G (p.Asp619Gly) TSHR gene-activating variant: relapsing hyperthyroidism in three subsequent generations manifesting in early childhood and an in vitro functional study.

Hormones (Athens) 2021 Jun 18. Epub 2021 Jun 18.

Vera Vavrova Laboratory/VIAL, Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.

Background: Familial non-autoimmune hyperthyroidism is a rare disease caused by germline activating variants in the thyroid-stimulating hormone receptor (TSHR) gene. The c.1856A > G (p.Asp619Gly) pathogenic variant has been described in cases of toxic adenoma but never before, to our knowledge, in a case of familial non-autoimmune hyperthyroidism.

Patient Findings: A 3-year-old boy was admitted for acute gastroenteritis presenting with goiter and tall stature. Laboratory findings revealed peripheral hyperthyroidism and negativity for thyroid autoantibodies. Antithyroid drug treatment was effective, but relapses occurred shortly after attempts to decrease the drug dose. As the boy's father and paternal grandmother also experienced relapsing hyperthyroidism manifesting in early childhood, genetic testing of TSHR was indicated. The c.1856A > G (p.Asp619Gly) pathogenic variant was found in all three affected family members. Functional in vitro characterization of the variant verified that it enhances constitutional activation of the receptor, leading to increased production of cyclic adenosine monophosphate. Total thyroidectomy was indicated in the boy due to an unsatisfactory prognosis. Due to persistent positive thyroglobulin serum concentration, a diagnostic radioiodine scan was performed approximately 2 years later. Residual thyroid tissue was revealed; therefore, radioiodine ablative therapy was performed. Despite adequate thyroxine substitution over a long period of follow-up, TSH remained suppressed.

Conclusions: Unlike Graves' disease, familial non-autoimmune hyperthyroidism cases present with antithyroid drug-dependence. Not ultrasound but positive thyroglobulin serum concentration indicated residual thyroid tissue. Early detection of residual thyroid tissue and radioiodine ablation prevented the subject from experiencing relapsing hyperthyroidism and undergoing unnecessary repeated surgery. Life-long hormone substitution should be adjusted to free thyroxine rather than TSH serum concentrations.
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http://dx.doi.org/10.1007/s42000-021-00299-xDOI Listing
June 2021

Macrophage inflammatory protein-1α in amniotic and cervical fluids in spontaneous preterm labor with intact membranes with respect to intra-amniotic inflammation.

J Matern Fetal Neonatal Med 2021 May 9:1-9. Epub 2021 May 9.

Institute of Clinical Immunology and Allergy, University Hospital Hradec Kralove, Charles University, Faculty of Medicine in Hradec Kralove, Hradec Kralove, Czech Republic.

Objective: Macrophage inflammatory protein 1α is a chemokine produced by various immune, epithelial, mesothelial, and fibroblast cells after exposure to bacterial lipopolysaccharide or pro-inflammatory molecules. The primary aim of this study was to determine MIP-1α concentrations in amniotic and cervical fluids from pregnancy with spontaneous preterm labor with intact membranes (PTL) with respect to the presence of intra-amniotic infection (both microbial invasion of the amniotic cavity and intra-amniotic inflammation) and sterile intra-amniotic inflammation (intra-amniotic inflammation alone). The secondary aim was to assess the diagnostic indices of MIP-1α in predicting intra-amniotic infection.

Materials And Methods: Seventy-four women with PTL were included in this study. Paired amniotic and cervical fluid samples were obtained using transabdominal amniocentesis and a Dacron polyester swab, respectively. Microbial invasion of the amniotic cavity was diagnosed based on a combination of culture and molecular biology methods. The concentration of IL-6 in the amniotic and cervical fluids was measured using an automated electrochemiluminescence immunoassay method. Intra-amniotic inflammation was defined as an amniotic fluid IL-6 concentration of ≥3000 pg/mL. The MIP-1α concentrations in the samples were assessed using an enzyme-linked immunosorbent assay.

Results: A difference in amniotic fluid MIP-1α was observed among women with intra-amniotic infection, sterile intra-amniotic inflammation, and negative amniotic fluid (infection: median 1779.0 pg/mL; sterile, median 102.7 pg/mL; negative, median 19.9 pg/mL;  < .0001). No difference in the concentrations of MIP-1α was identified in cervical fluid after adjustment for gestational age at sampling (infection: median 77.7 pg/mL, sterile: median 152.7 pg/mL, negative: median 18.0 pg/mL;  = .30). The presence of intra-amniotic infection was associated with elevated MIP-1α concentrations in amniotic fluid (presence: 1779.0 pg/mL vs. absence: 26.3 pg/mL,  < .0001, area under receiver operating characteristic curve = 0.87).

Conclusions: In PTL pregnancies with the presence of intra-amniotic infection, the concentration of MIP-1α is elevated in amniotic fluid but not in cervical fluid. Amniotic fluid MIP-1α may provide a useful marker for intra-amniotic infection in women with PTL.
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http://dx.doi.org/10.1080/14767058.2021.1922381DOI Listing
May 2021

IgGFc-binding protein in pregnancies complicated by spontaneous preterm delivery: a retrospective cohort study.

Sci Rep 2021 Mar 17;11(1):6107. Epub 2021 Mar 17.

Department of Clinical Immunology and Allergy, University Hospital Hradec Kralove, Charles University, Faculty of Medicine in Hradec Kralove, Hradec Králové, Czech Republic.

To determine the IgGFc-binding protein (FcgammaBP) concentration in amniotic and cervical fluids in preterm prelabor rupture of membranes (PPROM) and preterm labor with intact membranes (PTL) and to assess the diagnostic indices of FcgammaBP to predict intra-amniotic infection (the presence of both microbial invasion of the amniotic cavity and intra-amniotic inflammation). In this study, we included 170 and 79 women with PPROM and PTL, respectively. Paired cervical and amniotic fluid samples were obtained using a Dacron polyester swab and transabdominal amniocentesis, respectively. The FcgammaBP concentrations in the samples were assessed using an enzyme-linked immunosorbent assay. The presence of intra-amniotic infection was associated with elevated FcgammaBP concentrations in pregnancies with PPROM and PTL [PPROM-presence: 86 ng/mL vs. absence: 13 ng/mL, p < 0.0001, area under receiver operating characteristic curve (AUC) = 0.94; PTL-presence: 140 ng/mL vs. absence: 22 ng/mL, p < 0.0001, AUC = 0.86]. In cervical fluid, the concentrations of FcgammaBP were elevated in the presence of intra-amniotic infection in pregnancies with PPROM only (presence: 345 ng/mL vs. absence: 60 ng/mL, p < 0.0001, AUC = 0.93). FcgammaBP in amniotic fluid might be a marker of intra-amniotic infection in women with both PPROM and PTL However, in cervical fluid, it is only observed in women with PPROM.
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http://dx.doi.org/10.1038/s41598-021-85473-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969627PMC
March 2021

Haplotype analysis of the X chromosome in patients with Turner syndrome in order to verify the possible effect of imprinting on selected symptoms.

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2021 Jan 12. Epub 2021 Jan 12.

Department of Medical Genetics, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Czech Republic.

Aims: Turner syndrome is the only chromosome monosomy that is postnatally compatible with life. The reported incidence of TS is 1 in 2500 liveborn girls. The phenotype of these girls is highly variable, with cardiac abnormalities being life-threatening defects. The aim of the study was to reveal the possible influence of the parental origin of the X chromosome in these patients on a selected phenotype that is associated with Turner syndrome. Selected symptoms and parameters were: a bicuspid aortic valve, aortic coarctation, lymphoedema, pterygium colli, coeliac disease, thyroiditis, otitis media, diabetes mellitus 2, renal abnormalities, spontaneous puberty, and IVF.

Methods: The X chromosome haplotype was determined for a group of 45,X patients verified by native FISH. A molecular diagnostic method based on the detection of different lengths of X chromosome-linked STR markers using the Argus X-12 QS kit was used to determine the X haplotype.

Results: Our results, analysed by Fisher's exact (factorial) test, suggest independence between the maternal/paternal origin of the inherited X chromosome and the presence of the anomalies that were studied (P=1 to P=0.34).

Conclusion: In the group of 45,X patients, who were precisely selected by means of the native FISH method, no correlation was demonstrated with the parental origin of the X chromosome and the observed symptom.
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http://dx.doi.org/10.5507/bp.2020.060DOI Listing
January 2021

Intra-amniotic infection and sterile intra-amniotic inflammation are associated with elevated concentrations of cervical fluid interleukin-6 in women with spontaneous preterm labor with intact membranes.

J Matern Fetal Neonatal Med 2021 Jan 7:1-9. Epub 2021 Jan 7.

Department of Obstetrics and Gynecology, University Hospital Hradec Kralove, Charles University, Faculty of Medicine in Hradec Kralove, Hradec Kralove, Czech Republic.

Objective: To determine the concentration of interleukin-6 (IL-6) in the cervical fluid in women with spontaneous preterm labor with intact fetal membranes (PTL) complicated by intra-amniotic infection (the presence of both microbial invasion of the amniotic cavity and intra-amniotic inflammation), or sterile intra-amniotic inflammation (the presence of intra-amniotic inflammation alone).

Methods: Eighty women with singleton pregnancies complicated by PTL between gestational ages 22 + 0 and 34 + 6 weeks were included in this retrospective cohort study. Samples of amniotic and cervical fluids were collected at the time of admission. Amniotic fluid samples were obtained via transabdominal amniocentesis, and cervical fluid was obtained using a Dacron polyester swab. Microbial invasion of the amniotic cavity was diagnosed based on the combination of culture and molecular biology methods. The concentration of IL-6 in the amniotic and cervical fluids were measured using an automated electrochemiluminescence immunoassay method. Intra-amniotic inflammation was defined as an amniotic fluid IL-6 concentration ≥3000 pg/mL.

Results: The presence of intra-amniotic infection and sterile inflammation was identified in 15% (12/80) and 26% (21/80) of the women, respectively. Women with intra-amniotic infection (median: 587 pg/mL;  = .01) and with sterile intra-amniotic inflammation (median: 590 pg/mL;  = .005) had higher concentrations of IL-6 in the cervical fluid than those without intra-amniotic inflammation (intra-amniotic infection: median 587 pg/mL vs. without inflammation, median: 136 pg/mL;  = .01; sterile intra-amniotic inflammation, median: 590 pg/mL vs. without inflammation,  = .005). No differences were found in the concentrations of IL-6 in the cervical fluid between women with intra-amniotic infection and sterile intra-amniotic inflammation ( = .81).

Conclusion: In pregnancies with PTL, both forms of intra-amniotic inflammation are associated with elevated concentrations of IL-6 in the cervical fluid.
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http://dx.doi.org/10.1080/14767058.2020.1869932DOI Listing
January 2021

Extracellular granzyme A in amniotic fluid is elevated in the presence of sterile intra-amniotic inflammation in preterm prelabor rupture of membranes.

J Matern Fetal Neonatal Med 2020 Sep 10:1-10. Epub 2020 Sep 10.

Department of Obstetrics and Gynecology, University Hospital Hradec Kralove, Charles University, Faculty of Medicine in Hradec Kralove, Hradec Kralove, Czech Republic.

Introduction: To determine the levels of granzyme A in amniotic fluid in pregnancies complicated by preterm prelabor rupture of membranes (PPROM), based on the presence of microbial invasion of the amniotic cavity (MIAC) and/or intra-amniotic inflammation (IAI).

Methods Of Study: A total of 166 women with singleton pregnancies complicated by PPROM were included. Amniocentesis was performed at the time of admission and assessments of MIAC (using both cultivation and non-cultivation techniques) and IAI (interleukin-6 in amniotic fluid) were performed on all subjects. Based on the presence/absence of MIAC and IAI, the women were further divided into the following subgroups: intra-amniotic infection, sterile IAI, colonization, and absence of both MIAC and IAI. Amniotic fluid granzyme A levels were assessed using ELISA.

Results: Women with MIAC had lower levels of granzyme A in the amniotic fluid than women without this condition (with MIAC: median 15.9 pg/mL vs. without MIAC: median 19.9 pg/mL,  = .03). Women with sterile IAI had higher amniotic fluid granzyme A levels than women with intra-amniotic infection, colonization and women with the absence of either MIAC or IAI (intra-amniotic infection: median 15.6 pg/mL; sterile IAI: median 31.8 pg/mL; colonization: median 16.9 pg/mL; absence of both MIAC and IAI: median 18.8 pg/mL;  = .02).

Conclusions: The presence of sterile IAI was associated with elevated levels of granzyme A in amniotic fluid.
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http://dx.doi.org/10.1080/14767058.2020.1817895DOI Listing
September 2020

The role of the immune system and the biomarker CD3 + CD4 + CD45RA-CD62L- in the pathophysiology of migraine.

Sci Rep 2020 07 23;10(1):12277. Epub 2020 Jul 23.

Department of Neurology, Faculty of Medicine, University Hospital Hradec Králové, Charles University, Sokolská 581, Prague, Hradec Králové, 500 05, Czech Republic.

The role of the immune system as an integral component of the inflammatory response in the pathophysiology of migraine remains unclear. The aim of this study was to evaluate the differences in immune system parameters (acquired immunity parameters) in patients with episodic migraine (EM) and in healthy controls. In EM patients, we aimed to determine whether the changes found in peripheral blood parameters were related to migraine severity according to the standardised MIDAS and HIT-6 tests. Forty-nine patients with EM and 50 healthy controls were included in this study. The authors compared different lymphocyte parameters obtained by multicolor flow cytometry in the EM and control groups by performing statistical tests. The relationship between the changes in peripheral blood parameters and migraine severity in EM patients was investigated using correlation and regression analysis. EM patients showed higher values than healthy controls, especially in nine parameters: relative count of lymphocytes, relative and absolute counts of CD3 T cells, relative and absolute counts of CD8 suppressor cytotoxic T cells, relative and absolute counts of CD4 + T (terminally differentiated helper T lymphocytes), absolute count of CD8 naïve T cells, and absolute count of CD19 switched memory B cells. Among the lymphocyte parameters, CD4 + T (effector memory helper T lymphocytes) and CD8 + T (terminally differentiated cytotoxic T lymphocytes) were statistically significantly associated with HIT-6. Patients with a CD4 + T value below 15 had a high probability (90%) that the HIT-6 value would be higher than 60. The results of this study show that EM patients have changes in immune system parameters measured in the peripheral blood. Changes in the abundance of CD4 + T could be used as a biomarker for disease severity.
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http://dx.doi.org/10.1038/s41598-020-69285-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378179PMC
July 2020

Amniotic fluid CD11b levels in pregnancies complicated by preterm prelabor rupture of membranes.

J Matern Fetal Neonatal Med 2020 May 19:1-9. Epub 2020 May 19.

Department of Clinical Immunology and Allergy, University Hospital Hradec Kralove, Charles University, Hradec Kralove, Czech Republic.

CD11b is an integrin molecule located on the surface of leukocytes. CD11b is involved in the processes of cell adhesion and migration. Expression of CD11b increases during inflammation. Therefore, this study was aimed at the evaluation of concentrations of CD11b in the amniotic fluid from pregnancies complicated by preterm prelabor rupture of the membranes (PPROM), with respect to the presence of microbial invasion of the amniotic cavity (MIAC), intra-amniotic inflammation (IAI), and microbial-associated IAI (the presence of both MIAC and IAI). Eighty women with singleton pregnancies complicated by PPROM were included. Amniotic fluid samples were obtained by transabdominal amniocentesis. Amniotic fluid CD11b concentrations were determined by enzyme-linked immunosorbent assay. MIAC was determined by a non-cultivation approach. IAI was defined by a bedside amniotic fluid interleukin-6 concentration ≥745 pg/mL. Women with MIAC or microbial-associated IAI had higher CD11b concentrations in the amniotic fluid than women without these complications (with MIAC: median 0.31 ng/mL versus without MIAC: median 0.17 ng/mL,  = .001; with microbial associated-IAI: median 0.35 ng/mL versus without microbial-associated IAI: median 0.16 ng/mL;  =.02). The presence of IAI was not associated with elevated CD11b concentrations. A weak negative correlation was found between amniotic fluid CD11b concentrations and interleukin-6 concentrations (rho = 0.26;  = .02). MIAC and microbial-associated IAI are characterized by higher amniotic fluid CD11b concentrations in pregnancies complicated by PPROM.
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http://dx.doi.org/10.1080/14767058.2020.1767578DOI Listing
May 2020

Innate Immune System and Multiple Sclerosis. Granulocyte Numbers Are Reduced in Patients Affected by Relapsing-Remitting Multiple Sclerosis during the Remission Phase.

J Clin Med 2020 May 14;9(5). Epub 2020 May 14.

Department of Neurology, Faculty of Medicine and University Hospital Hradec Králové, Charles University in Prague, Sokolská 581, 500 05 Hradec Kralove, Czech Republic.

Background: Multiple sclerosis (MS) is a neurodegenerative disease that affects the central nervous system. The cause of MS is still unknown, and the role of innate immunity is still poorly understood.

Objective: The goal of this study was to understand whether, compared to healthy controls, the elements of innate immunity are altered in the blood of MS patients in the remitting phase.

Methods: A total of 77 naïve MS patients and 50 healthy controls were included in this cohort study. Peripheral blood samples were collected and analyzed. All the calculations were performed with the statistical system R (r-project.org).

Results: The results showed that MS patients had significantly lower relative representations of granulocytes than healthy controls, while the relative representations of monocytes remained unchanged. CD64- and PD-L1-positive granulocytes exhibited a nonsignificant decreasing trend, while granulocytes with other membrane markers remained noticeably unchanged.

Conclusion: The results of this study suggest that studies of the causes of MS and its treatment should also be focused on the elements of the innate immune response.
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http://dx.doi.org/10.3390/jcm9051468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290702PMC
May 2020

Primary School Performance of Girls with Turner Syndrome: A Transcultural Assessment.

Pediatr Endocrinol Rev 2019 Dec;17(2):117-124

Department of Pediatrics, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.

Objectives: We analyzed primary school performance of girls with Turner syndrome (TS) in two distinct countries to ascertain if the cognitive phenotype of TS causes selective learning difficulties.

Methods: The cohort comprised of 44 Czech and 50 Egyptian girls with TS who attended public schools. School reports from grades 1 to 9 were obtained retrospectively from Czech participants with TS. Only recent school reports were obtained from Egyptian participants. Two controls per participant were requested - biological sisters and/or female classmates. The results were converted into a 5-point scale (1-excellent; 5-unsatisfactory).

Results: Analysis of longitudinal Czech data displayed a strong time component in both subjects and controls. Showing better points in lower grades with its gradual worsening as the education complexity increased. In contrast, there was a strong statistically significant difference between groups in Mathematics (p=0.0041, p=0.0205 after Bonferroni correction) and this difference increased over time. The points for Mathematics did not differ in grades 1+2 (0.05 difference in mean grade between the two groups), however, they differed by 0.28 in grades 6+7 and by 0.32 in grades 8+9. While slightly different in character (cross-sectional vs. longitudinal), the Egyptian cohort data confirmed our findings, showing no difference in general school performance but having similar trends in Mathematics (grades 1+2: 0.11, grades 6+7: 0.54, grades 8+9: 0.68; p=0.0058, p=0.029 after Bonferroni correction).

Conclusion: Excluding results in Mathematics, which showed pronounced worsening in relation to age in comparison with unaffected controls, girls with TS performed similarly to their controls.
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http://dx.doi.org/10.17458/per.vol17.2019.lhs.gilrsturnersyndromeDOI Listing
December 2019

An isolated Xp deletion is linked to autoimmune diseases in Turner syndrome.

J Pediatr Endocrinol Metab 2019 May;32(5):479-488

Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.

Background Females with Turner syndrome (TS) are prone to develop autoimmune diseases (AIDs). The X chromosome contains several immune-related genes. Growth hormone (GH) and estrogens modulate the immune system. We aimed to clarify whether the loss of a specific X chromosome gene locus and the administration of GH and estradiol facilitate the development of AIDs in TS females. Methods Retrospective data on clinical course, AIDs, karyotype and treatment were analyzed from a cohort of 286 Czech females with TS (current age 2.8-43.3 years; median age 18.7 years). The karyotypes were sorted using two different classification systems: a mosaicism-focused and an isochromosome (isoXq)-focused approach. Karyotype subgroups with a significantly higher prevalence of AIDs were further evaluated. Data of common therapies were correlated with the prevalence of AIDs. Results The most frequent AIDs were autoimmune thyroid disease (AITD; 37.4%; n = 107) and celiac disease (CD; 8.7%; n = 25). All karyotype subgroups were prone to develop AIDs. Females with an isolated Xp deletion had a significantly higher prevalence of AITD and CD compared to all other individuals with TS (AITD: 66.0% vs. 31.5%, p < 0.0001; CD: 17.4% vs. 7.2%; p = 0.04, respectively). We observed no link between the mean age at initiation as well as the duration of GH and/or estrogen administration and the occurrence of AIDs. Conclusions Isolated Xp deletion contributes to the development of AIDs in TS patients. The haploinsufficiency of genes located in Xpter-p11.2 may explain this observation. Common therapies used in TS do not modify the risk of AIDs.
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http://dx.doi.org/10.1515/jpem-2019-0067DOI Listing
May 2019

Immunohistochemical diagnostics of Hirschprungs disease using calretinin.

Cesk Patol 2019 ;55(1):53-59

Histochemical diagnosis of Hirschsprung´s disease at our institution was introduced in the 1970s, calretinin imunohistochemistry on formalin fixed tissue was newly added in 2015. Employing both methods we were able to confirm Hirschsprung´s disease in 13 patients and exclude it in 34 patients since then. Calretinin seems highly reliable and easy to evaluate, it is not influenced by patient´s age, associated genetic features or the length of agangliosis. The number of inadequate samples was very low (3.8%). Histochemistry is useful as an adjunct tool to correct equivocal findings of calretinin staining and to facilitate diagnosis of short and ultra-short Hirschsprung´s disease. Serial biopsies from distal rectum and adjacent large bowel were obtained to assess the length of agangliosis preoperatively. The results of calretinin imunohistochemistry correlated very well with the findings in the colectomy specimens. In contrast, the length of affected bowel detected by histochemistry was often underestimated because acetylcholinesterase activity always diminishes orally irrespective of the length of aganglionic portion.
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June 2019

A 6-Year Follow-Up of Fracture Incidence and Volumetric Bone Mineral Density Development in Girls With Turner Syndrome.

J Clin Endocrinol Metab 2018 03;103(3):1188-1197

Department of Pediatrics, Second Medical Faculty, Charles University in Prague and Motol University Hospital, Prague, Czech Republic.

Context: Patients with Turner syndrome (TS) are at risk for osteoporotic fractures.

Objective: The aims of this study were to assess the incidence of clinically important fractures in girls with TS and prospectively describe the development of volumetric bone mineral density (BMD).

Design: Peripheral quantitative computerized tomography (pQCT) of the radius every other year over the 6 years of observation.

Setting: Government-funded university referral center.

Participants: Thirty-two girls with TS, aged 6 to 16 years, were included in the analyses. Fracture incidence was compared with the data in the general population. Bone density and strength were compared with data from 185 healthy girls.

Outcomes: The main clinical outcome was the fracture occurrence. The secondary outcomes were the changes in Z-scores of the bone parameters.

Results: Three girls with TS sustained four fractures during 6 years of observation. The fracture rate in TS was not substantially higher than the downward-biased fracture-rate estimate from age-matched, healthy controls (P = 0.48). Whereas the trabecular BMD Z-score decreased with age (β estimate -0.21 ± 0.04, P < 0.001), total bone cross-sectional area correspondingly increased (+0.16 ± 0.04, P < 0.001), which led to normal bone strength. A positive history of incident fractures was not significantly associated with any of the pQCT-derived bone parameters.

Conclusions: Current pediatric TS patients that are treated with growth hormone and estrogens are not at risk for osteoporotic fractures. Low BMD in TS may be counterweighted by enlarged bone radius, which leads to normal bone strength at the appendicular skeleton.
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http://dx.doi.org/10.1210/jc.2017-02381DOI Listing
March 2018

Animal models to explore the effects of glucocorticoids on skeletal growth and structure.

J Endocrinol 2018 Jan 19;236(1):R69-R91. Epub 2017 Oct 19.

Developmental Endocrinology Research GroupSchool of Medicine, University of Glasgow, Glasgow, UK

Glucocorticoids (GCs) are effective for the treatment of many chronic conditions, but their use is associated with frequent and wide-ranging adverse effects including osteoporosis and growth retardation. The mechanisms that underlie the undesirable effects of GCs on skeletal development are unclear, and there is no proven effective treatment to combat them. An model that investigates the development and progression of GC-induced changes in bone is, therefore, important and a well-characterized pre-clinical model is vital for the evaluation of new interventions. Currently, there is no established animal model to investigate GC effects on skeletal development and there are pros and cons to consider with the different protocols used to induce osteoporosis and growth retardation. This review will summarize the literature and highlight the models and techniques employed in experimental studies to date.
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http://dx.doi.org/10.1530/JOE-17-0361DOI Listing
January 2018

Muscle functions and bone strength are impaired in adolescents with type 1 diabetes.

Bone 2018 Jan 7;106:22-27. Epub 2017 Oct 7.

Department of Pediatrics, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, V Uvalu 84, 150 06 Prague 5, Czech Republic. Electronic address:

Background: Sarcopenia and osteoporosis are among the late complications of type 1 diabetes (T1D) in adults. Whether and to what extent musculoskeletal impairment is present in childhood and adolescence has yet to be determined. The aim of this study was to assess volumetric bone mineral density (BMD) and dynamic muscle function in adolescents with T1D and to assess the clinical and biochemical predictors of their musculoskeletal system.

Methods: Ninety-five children and adolescents (59 boys and 36 girls, mean age 16.2±1.2years) with T1D were included in this cross-sectional study. Study participants were divided into two groups according to the duration of the disease (<6years and >9years, respectively). Volumetric BMD of the non-dominant tibia was assessed using peripheral quantitative computed tomography (pQCT). Dynamic muscle function was evaluated using jumping mechanography. Gender- and height-specific Z-scores were calculated using published reference data. HbA1c was evaluated retrospectively as an average over the past 5years.

Results: Relative muscle power (P/mass) and force (F/body weight) were significantly decreased in T1D subjects (mean Z-scores -0.4±1.0; p<0.001, and -0.3±1.1; p<0.01, respectively). The duration of T1D negatively affected P/mass (p<0.01) but not F/body weight (p=0.54). Patients with T1D had also decreased trabecular BMD, the Strength-Strain Index and cortical thickness (mean Z-scores -0.8±1.3; -0.5±0.8 and -1.1±0.8, respectively, p<0.001 for all) whereas cortical BMD was increased when compared to controls (Z-score 1.2±0.90, p<0.001). No association was observed between the HbA1c and 25-hydroxyvitamin D levels and bone or muscle parameters.

Conclusion: T1D influences the musculoskeletal system in adolescence. Decreased muscle function could contribute to the osteoporosis reported in adult diabetic patients.
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http://dx.doi.org/10.1016/j.bone.2017.10.005DOI Listing
January 2018

Musculoskeletal system in children and adolescents with inflammatory bowel disease: normal muscle force, decreased trabecular bone mineral density and low prevalence of vertebral fractures.

Eur J Pediatr 2017 Oct 24;176(10):1355-1363. Epub 2017 Aug 24.

Department of Pediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, V Uvalu 84, 150 06, Prague 5, Czech Republic.

Low bone mineral density (BMD) and an increased fracture incidence are two extraintestinal complications associated with inflammatory bowel disease (IBD). We aimed to evaluate musculoskeletal traits and assess vertebral fracture (VF) rate in children and adolescents with IBD. Seventy patients with IBD with a median age of 13.8 years were included. The BMD and geometric parameters of the non-dominant tibia were assessed using pQCT. Dynamic muscle functions were evaluated using jumping mechanography. VFs were assessed according to the semiquantitative standardized method by Genant. The muscle functions adjusted for the patients' weight did not differ from the reference population. A low trabecular BMD (Z-score - 1.6; p < 0.001) and cortical thickness (Z-score - 0.7; p < 0.001) were found in children and adolescents with IBD. Conversely, an increased cortical BMD (Z-score 1.1; p < 0.001) was noted. No significant association was found between the 25-OHD serum levels and the bone or muscle measurements. One patient with asymptomatic VF was identified.

Conclusion: IBD in childhood or adolescents affects bones but not muscles. Bone changes are independent of the 25-OHD serum level. A thoracolumbar spine X-ray should not be routinely recommended in children with IBD. What is Known: • Low bone mineral density and an increased fracture rate are the complications associated with IBD. • Bone strength and structural development is strongly dependent on skeletal muscle stimulation. What is New: • Children with IBD have altered bone density and geometry but normal dynamic muscle functions. • Thoracolumbar spine X-ray should be indicated on an individual basis in children with IBD.
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http://dx.doi.org/10.1007/s00431-017-2988-7DOI Listing
October 2017

Plume Activity and Tidal Deformation on Enceladus Influenced by Faults and Variable Ice Shell Thickness.

Astrobiology 2017 Sep 17;17(9):941-954. Epub 2017 Aug 17.

1 Charles University , Faculty of Mathematics and Physics, Department of Geophysics, Prague, Czech Republic .

We investigated the effect of variations in ice shell thickness and of the tiger stripe fractures crossing Enceladus' south polar terrain on the moon's tidal deformation by performing finite element calculations in three-dimensional geometry. The combination of thinning in the polar region and the presence of faults has a synergistic effect that leads to an increase of both the displacement and stress in the south polar terrain by an order of magnitude compared to that of the traditional model with a uniform shell thickness and without faults. Assuming a simplified conductive heat transfer and neglecting the heat sources below the ice shell, we computed the global heat budget of the ice shell. For the inelastic properties of the shell described by a Maxwell viscoelastic model, we show that unrealistically low average viscosity of the order of 10 Pa s is necessary for preserving the volume of the ocean, suggesting the important role of the heat sources in the deep interior. Similarly, low viscosity is required to predict the observed delay of the plume activity, which hints at other delaying mechanisms than just the viscoelasticity of the ice shell. The presence of faults results in large spatial and temporal heterogeneity of geysering activity compared to the traditional models without faults. Our model contributes to understanding the physical mechanisms that control the fault activity, and it provides potentially useful information for future missions that will sample the plume for evidence of life. Key Words: Enceladus-Tidal deformation-Faults-Variable ice shell thickness-Tidal heating-Plume activity and timing. Astrobiology 17, 941-954.
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http://dx.doi.org/10.1089/ast.2016.1629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5610426PMC
September 2017

Cervical fluid interleukin 6 and intra-amniotic complications of preterm prelabor rupture of membranes.

J Matern Fetal Neonatal Med 2018 Apr 9;31(7):827-836. Epub 2017 Mar 9.

a Department of Obstetrics and Gynecology , Charles University in Prague, Faculty of Medicine Hradec Kralove, University Hospital Hradec Kralove , Hradec Kralove , Czech Republic.

Objective: To determine if cervical fluid interleukin (IL)-6 concentrations in women with preterm prelabor rupture of membranes (PPROM) allows identification of microbial invasion of the amniotic cavity (MIAC) and/or intra-amniotic inflammation (IAI).

Methods: One hundred forty-four women with singleton pregnancies complicated by PPROM were included in this prospective cohort study. Cervical and amniotic fluids were collected at the time of admission and concentrations of IL-6 were measured using an ELISA and point-of-care test, respectively. Cervical fluid was obtained using a Dacron polyester swab and amniotic fluid was obtained by transabdominal amniocentesis. MIAC was diagnosed based on a positive PCR result for Ureaplasma species, M. hominis, and/or C. trachomatis and/or by positivity for the 16 S rRNA gene. IAI was defined as amniotic fluid point-of-care IL-6 concentrations ≥745 pg/mL. The women were assigned to four subgroups based on the presence of MIAC and/or IAI: microbial-associated IAI (both MIAC and IAI), sterile IAI (IAI alone), MIAC alone, and without either MIAC or IAI.

Results: (1) Women with microbial-associated IAI had higher cervical fluid IL-6 concentrations (median 560 pg/mL) than did women with sterile IAI (median 303 pg/mL; p = .001), women with MIAC alone (median 135 pg/mL; p = .0004), and women without MIAC and IAI (median 180 pg/mL; p = .0001). (2) No differences were found in cervical fluid IL-6 concentrations among women with sterile IAI, with MIAC alone, and without MIAC and IAI. (3) A positive correlation was observed between cervical fluid IL-6 concentrations and the amount of Ureaplasma species in amniotic fluid (copies DNA/mL; rho = 0.57, p < .0001). (4) A weak positive correlation was detected between cervical and amniotic fluid IL-6 concentrations (rho = 0.33, p < .0001).

Conclusions: The presence of microbial-associated IAI is associated with the highest cervical fluid IL-6 concentrations. Cervical IL-6 can be helpful in the identification of microbial-associated IAI.
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http://dx.doi.org/10.1080/14767058.2017.1297792DOI Listing
April 2018

Supplementation with 2000 IU of Cholecalciferol Is Associated with Improvement of Trabecular Bone Mineral Density and Muscle Power in Pediatric Patients with IBD.

Inflamm Bowel Dis 2017 04;23(4):514-523

Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic.

Background: Inflammatory bowel diseases (IBD) are associated with altered bone health and increased risk for fractures. Vitamin D deficiency is frequently found in IBD; however, the effect of vitamin D supplementation on bone health of children with IBD is poorly understood. We aimed to observe the changes in volumetric bone density and dynamic muscle functions after vitamin D substitution in a cohort of pediatric patients with IBD.

Methods: This was a prospective observational study of 55 patients (aged 5-19 years) with IBD. Bone quality was assessed using peripheral quantitative computed tomography and muscle functions by jumping mechanography at baseline and after a median of 13.8 (interquartile range, 12.0-16.0) months of daily substitution of 2000 IU of cholecalciferol.

Results: Median serum levels of 25-hydroxyvitamin D increased from 58 nmol/L at the baseline visit to 85 nmol/L at the last follow-up visit (P < 0.001); no signs of overdose were reported. The Z-scores of trabecular bone mineral density, cortical bone cross-sectional area, and maximal muscle power improved significantly during the follow-up period (+0.5, P = 0.001, +0.3, P = 0.002 and +0.5, P = 0.002, respectively). Cholecalciferol substitution was positively associated with trabecular bone mineral density and maximal muscle power (estimates 0.26, 95% confidence interval 0.14-0.37, P < 0.0001 and 0.60, 95% confidence interval 0.32-0.85, P < 0.0001, respectively) but not with the Strength-Strain Index or maximal muscle force (Fmax).

Conclusions: We observed an improvement in bone and muscle parameters after cholecalciferol substitution in pediatric patients with IBD. Therefore, vitamin D substitution can be considered in such patients.
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http://dx.doi.org/10.1097/MIB.0000000000001047DOI Listing
April 2017

Cervical fluid calreticulin and cathepsin-G in pregnancies complicated by preterm prelabor rupture of membranes.

J Matern Fetal Neonatal Med 2018 Feb 28;31(4):481-488. Epub 2017 Feb 28.

b Department of Obstetrics and Gynecology , Charles University in Prague, Faculty of Medicine Hradec Kralove, University Hospital Hradec Kralove , Hradec Kralove , Czech Republic.

Objective: The study aimed to determine the cervical calreticulin and cathepsin-G concentrations in pregnancies complicated by preterm prelabor rupture of membranes (PPROM) with respect to the presence of microbial invasion of the amniotic cavity (MIAC) and intra-amniotic inflammation (IAI).

Methods: Eighty women with singleton pregnancies complicated by PPROM were included in this study. Cervical and amniotic fluids were obtained at the time of admission, and concentrations of calreticulin and cathepsin-G in cervical fluid were determined using ELISA. The MIAC was defined as a positive PCR analysis for Ureaplasma species, Mycoplasma hominis, and/or Chlamydia trachomatis and/or by positivity for the 16S rRNA gene. IAI was defined as amniotic fluid bedside IL-6 concentrations ≥745 pg/mL Result: Neither women with MIAC nor with IAI had different cervical fluid concentrations of calreticulin (with MIAC: median 18.9 pg/mL vs. without MIAC: median 14.7 pg/mL, p = 0.28; with IAI: median 14.3 pg/mL vs. without IAI: median 15.6 pg/mL, p = 0.57;) or of cathepsin-G (with MIAC: median 30.7 pg/mL vs. without MIAC: median 24.7 pg/mL, p = 0.28; with IAI: median 27.3 pg/mL vs. without IAI: median 25.1 pg/mL, p = 0.80) than women without those complications. No associations between amniotic fluid IL-6 concentrations, gestational age at sampling, and cervical fluid calreticulin and cathepsin-G concentrations were found.

Conclusions: Cervical fluid calreticulin and cathepsin-G concentrations did not reflect the presence of MIAC or IAI in women with PPROM.
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http://dx.doi.org/10.1080/14767058.2017.1288209DOI Listing
February 2018

Amniotic fluid clusterin in pregnancies complicated by the preterm prelabor rupture of membranes.

J Matern Fetal Neonatal Med 2017 Nov 22;30(21):2529-2537. Epub 2016 Nov 22.

a Department of Obstetrics and Gynecology , Charles University in Prague, Faculty of Medicine Hradec Kralove, University Hospital Hradec Kralove , Hradec Kralove , Czech Republic.

Objective: The aim of this study was to evaluate clusterin concentrations in amniotic fluid in pregnancies complicated by preterm prelabor rupture of membranes (PPROM) with respect to the presence of the microbial invasion of the amniotic cavity (MIAC), intra-amniotic inflammation (IAI) and microbial-associated IAI.

Methods: One hundred thirty-six women with singleton pregnancies complicated by PPROM were included in this study. Amniotic fluid samples were obtained by transabdominal amniocentesis. Amniotic fluid clusterin concentrations were assessed by enzyme-linked immunosorbent assay. MIAC was determined by a non-cultivation approach. IAI was defined as an amniotic fluid bedside interleukin-6 concentration ≥745 pg/mL. Microbial-associated IAI was characterized as the presence of both MIAC and IAI.

Result: Women with MIAC, IAI and microbial-associated IAI had lower amniotic fluid clusterin concentrations than women without these complications (with MIAC: median 1314 ng/mL versus without MIAC: median 1633 ng/mL, p = 0.003; with IAI: median 1281 ng/mL versus without IAI: median 1575 ng/mL, p = 0.04; with microbial associated-IAI: median 1220 ng/mL versus without microbial-associated IAI: median 1575 pg/mL; p = 0.008). A week negative correlation between amniotic fluid clusterin concentrations and gestational age at sampling was revealed (rho= -0.30; p = 0.0005).

Conclusions: The presence of MIAC, IAI and microbial-associated IAI was characterized by lower amniotic fluid clusterin concentrations in pregnancies complicated by PPROM.
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http://dx.doi.org/10.1080/14767058.2016.1255192DOI Listing
November 2017

Amniotic fluid cathepsin-G in pregnancies complicated by the preterm prelabor rupture of membranes.

J Matern Fetal Neonatal Med 2017 Sep 9;30(17):2097-2104. Epub 2016 Oct 9.

a Department of Obstetrics and Gynecology.

Objective: The aim of this study was to evaluate the amniotic fluid cathepsin-G concentrations in women with preterm prelabor rupture of membranes (PPROM) based on the presence of the microbial invasion of the amniotic cavity (MIAC) and/or intra-amniotic inflammation (IAI).

Methods: A total of 154 women with singleton pregnancies complicated by PPROM were included in this study. Amniotic fluid samples were obtained by transabdominal amniocentesis. Amniotic fluid cathepsin-G concentrations were assessed by ELISA. MIAC was determined using a non-cultivation approach. IAI was defined as an amniotic fluid bedside interleukin-6 concentration ≥ 745 pg/mL.

Results: Women with MIAC had higher amniotic fluid cathepsin-G concentrations than women without MIAC (with MIAC: median 82.7 ng/mL, versus without MIAC: median 64.7 ng/mL; p = 0.0003). Women with IAI had higher amniotic fluid cathepsin-G concentrations than women without this complication (with IAI: median 103.0 ng/mL, versus without IAI: median 66.2 ng/mL; p < 0.0001). Women with microbial-associated (with both MIAC and IAI) IAI and sterile (IAI without MIAC) IAI had higher amniotic fluid cathepsin-G concentrations than women with colonization (MIAC without IAI) and women without both MIAC and IAI (p < 0.0001).

Conclusions: The presence of either microbial-associated or sterile IAI was associated with increased amniotic fluid cathepsin-G concentrations in pregnancies complicated by PPROM. Amniotic fluid cathepsin-G appears to be a potential marker of IAI.
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http://dx.doi.org/10.1080/14767058.2016.1237499DOI Listing
September 2017

A Rare Variant of Turner Syndrome in Four Sequential Generations: Effect of the Interplay of Growth Hormone Treatment and Estrogens on Body Proportion.

Horm Res Paediatr 2016 27;86(5):349-356. Epub 2016 Jul 27.

Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, and GENNET, Prague, Czech Republic.

Background: Terminal Xp deletion leads to SHOX haploinsufficiency, and when it exceeds Xp22.33 it causes a variant of Turner syndrome (TS) in which gonadal function is preserved and short stature constitutes the major clinical feature.

Case Report: We present a family with vertical transmission of TS that affected six women in four sequential generations. The karyotype was defined as a combination of terminal Xp deletion and terminal Xq duplication: 46,X,rec(X)inv(p21.1q27.3). All affected women had short stature, but had developed spontaneous puberty and normal fertility. Generation IV exclusively received recombinant human growth hormone (rhGH). We investigated the effect of rhGH treatment on skeletal growth and body proportion via the comparison of auxological data from an untreated 39.7-year-old mother to her 14.8-year-old rhGH-treated daughter. The adult height of the daughter was substantially better than that of the mother [160.3 cm (-0.8 SDS) and 150.0 cm (-2.7 SDS), respectively]; however, the disproportion progressed following rhGH treatment and ultimately led to a worse trunk-to-extremities ratio compared with the mother (4.8 and 3.7 SDS, respectively).

Conclusion: This rare family confirms the vertical transmission of TS spanning multiple generations. The combination of endogenous estrogen production and exogenous rhGH administration in women with SHOX haploinsufficiency may worsen their body disproportion.
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http://dx.doi.org/10.1159/000448097DOI Listing
April 2017

Intraamniotic inflammation and umbilical cord blood interleukin-6 concentrations in pregnancies complicated by preterm prelabor rupture of membranes.

J Matern Fetal Neonatal Med 2017 Apr 20;30(8):900-910. Epub 2016 Jun 20.

a Department of Obstetrics and Gynecology , Faculty of Medicine, Charles University in Prague, Hradec Kralove, University Hospital Hradec Kralove , Hradec Kralove , Czech Republic.

Objective: To evaluate umbilical cord blood interleukin (IL)-6 concentrations and the occurrence of fetal inflammatory response syndrome (FIRS) with respect to microbial invasion of the amniotic cavity (MIAC) and/or intraamniotic inflammation (IAI) in pregnancies complicated by preterm prelabor rupture of membranes (PPROM).

Methods: One-hundred-eighty-eight women with singleton pregnancies complicated by PPROM between gestational ages of 24 + 0 and 36 + 6 weeks were included in the study. Blood samples were obtained by venipuncture from the umbilical cord after the delivery of the newborn. The umbilical cord blood IL-6 concentrations were evaluated using ELISA kits. FIRS was defined as umbilical cord blood IL-6 > 11 pg/mL.

Result: Women with MIAC and IAI had higher IL-6 concentrations than women without these complications (with MIAC: median 18.1 pg/mL versus without MIAC: median 5.8; p < 0.0001; with IAI: median 32.9 pg/mL, versus without IAI: median 5.8; p < 0.0001). Women with IAI with MIAC and women with IAI without MIAC had the highest umbilical cord blood IL-6 concentrations (medians: 32.6 and 39.4 pg/mL) and rates of FIRS (78% and 67%).

Conclusions: IAI was associated with the highest umbilical cord blood IL-6 concentrations and rate of FIRS independent of the presence or absence of MIAC.
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http://dx.doi.org/10.1080/14767058.2016.1197900DOI Listing
April 2017

Amniotic fluid calreticulin in pregnancies complicated by the preterm prelabor rupture of membranes.

J Matern Fetal Neonatal Med 2016 Dec 8;29(24):3921-9. Epub 2016 Mar 8.

a Department of Obstetrics and Gynecology , Faculty of Medicine Hradec Kralove, Charles University in Prague , Hradec Kralove , Czech Republic .

Objective: This study aimed to determine the amniotic fluid calreticulin concentrations in women with the preterm prelabor rupture of membranes (PPROM) based on the microbial invasion of the amniotic cavity (MIAC), intraamniotic inflammation (IAI) and microbial-associated IAI.

Methods: One hundred sixty-eight women with singleton pregnancies were included in this study. Amniotic fluid samples were obtained by transabdominal amniocentesis and were assayed for calreticulin concentrations by ELISA. IAI was defined as an amniotic fluid interleukin-6 concentration > 745 pg/ml. Microbial-associated IAI was defined as the presence of both MIAC and IAI.

Result: Women with MIAC (with MIAC: median 54.4 ng/ml, versus without MIAC: median 32.6 ng/ml; p < 0.0001), IAI (with IAI: median 66.8 ng/ml, versus without IAI: median 33.0 ng/ml; p < 0.0001) and microbial-associated IAI (with microbial-associated IAI: median 82.5 ng/ml, versus without microbial-associated IAI: median 33.7 ng/ml; p < 0.0001) had higher concentrations of calreticulin than women without these complications. An amniotic fluid calreticulin concentration of 81.4 ng/ml was found to be the best cutoff point for identifying women with microbial-associated IAI.

Conclusions: The presence of microbial-associated IAI is associated with increased amniotic fluid calreticulin concentrations. Calreticulin seems to be a promising marker for the early identification of PPROM complicated by microbial-associated IAI.
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http://dx.doi.org/10.3109/14767058.2016.1154940DOI Listing
December 2016

[Secondary humoral immunodeficiency in patiens with systemic lupus erythematosus].

Vnitr Lek 2015 Sep;61(9):778-84

Introduction: Systemic lupus erythematosus (SLE) is a chronic autoimmune multisystem disease. The aim of our study was to clarify the frequency of decreased serum immunoglobulin levels in SLE patients. There were evaluated 799 results of serum immunoglobulin levels gained from 157 patients fulfilling revised ACR criteria in the retrospective study.

Results: The immunoglobulin levels under the normal range were found in 29/157 (18.5 %) patients. The most frequent was isolated reduction of IgG 12/157 (7.6 %), two persons fulfilled criteria for selective IgA deficiency, and one case possible diagnosis of common variable immunodeficiency (CVID). Additionally we report two cases of SLE patients complicated by severe hypogammaglobulinaemia and infectious complications with necessity of long-term immunoglobulin substitution therapy. The diagnosis of CVID is highly probable in the first case. The second case presents sever drug-induced hypogammaglobulinaemia. This female with lymphoma history and multiorgan impairment due to acute SLE was treated with rituximab after convention therapy failure.

Conclusion: Humoral immunodeficiency may occur in SLE patients. The monitoring of serum immunoglobulin levels could be a routine in these patients. The CVID diagnosis is possible in patients suffering from recurrent sinopulmonary infections, especially in combination with absence of lupus activity. Rituximab therapy could cause long-term suppression of B lymphocytes with secondary humoral deficiency requiring immunoglobulin substitution therapy.
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September 2015

Hypophosphatasia due to uniparental disomy.

Bone 2015 Dec 1;81:765-766. Epub 2015 May 1.

Department of Biology and Medical Genetics, Charles University 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.

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http://dx.doi.org/10.1016/j.bone.2015.04.041DOI Listing
December 2015

The muscle-bone interaction in Turner syndrome.

Bone 2015 May 3;74:160-5. Epub 2015 Feb 3.

Department of Pediatrics, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic. Electronic address:

Objectives: Turner syndrome (TS) is associated with an increased fracture rate due to reduced bone strength, which is mainly determined by skeletal muscle force. This study aimed to assess the muscle force-bone strength relationship in TS and to compare it with that of healthy controls.

Methods: This study included 39 girls with TS and 67 healthy control girls. Maximum muscle force (Fmax) was assessed through multiple one-legged hopping with jumping mechanography. Peripheral quantitative computerized tomography assessed the bone strength index at the tibial metaphysis (BSI 4) and the polar strength-strain index at the diaphysis (SSI polar 66). The effect of TS on the muscle-bone unit was tested using multiple linear regression.

Results: TS had no impact on Fmax (p=0.14); however, a negative effect on bone strength (p<0.001 for BSI 4 and p<0.01 for SSI polar 66) was observed compared with healthy controls. Bone strength was lower in the TS group (by 18%, p<0.01, for BSI 4 and by 7%, p=0.027, for SSI polar 66), even after correcting for Fmax.

Conclusions: Similar muscle force induces lower bone strength in TS compared with healthy controls, which suggests altered bone-loading sensitivity in TS.
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http://dx.doi.org/10.1016/j.bone.2015.01.017DOI Listing
May 2015

Autosomal recessive limb-girdle muscular dystrophies in the Czech Republic.

BMC Neurol 2014 Aug 19;14:154. Epub 2014 Aug 19.

Centre of Molecular Biology and Gene Therapy, University Hospital Brno, Černopolní 9, Brno, 613 00, Czech Republic.

Background: Autosomal recessive limb-girdle muscular dystrophies (LGMD2) include a number of disorders with heterogeneous etiology that cause predominantly weakness and wasting of the shoulder and pelvic girdle muscles. In this study, we determined the frequency of LGMD subtypes within a cohort of Czech LGMD2 patients using mutational analysis of the CAPN3, FKRP, SGCA, and ANO5 genes.

Methods: PCR-sequencing analysis; sequence capture and targeted resequencing.

Results: Mutations of the CAPN3 gene are the most common cause of LGMD2, and mutations in this gene were identified in 71 patients in a set of 218 Czech probands with a suspicion of LGMD2. Totally, we detected 37 different mutations of which 12 have been described only in Czech LGMD2A patients. The mutation c.550delA is the most frequent among our LGMD2A probands and was detected in 47.1% of CAPN3 mutant alleles. The frequency of particular forms of LGMD2 was 32.6% for LGMD2A (71 probands), 4.1% for LGMD2I (9 probands), 2.8% for LGMD2D (6 probands), and 1.4% for LGMD2L (3 probands).Further, we present the first results of a new approach established in the Czech Republic for diagnosis of neuromuscular diseases: sequence capture and targeted resequencing. Using this approach, we identified patients with mutations in the DYSF and SGCB genes.

Conclusions: We characterised a cohort of Czech LGMD2 patients on the basis of mutation analysis of genes associated with the most common forms of LGMD2 in the European population and subsequently compared the occurrence of particular forms of LGMD2 among countries on the basis of our results and published studies.
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http://dx.doi.org/10.1186/s12883-014-0154-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4145250PMC
August 2014