Vitova L.,Teaching Hospital Motol |
Tuma Z.,Charles University |
Moravec J.,Charles University |
Kvapil M.,Teaching Hospital Motol |
And 2 more authors.
BMC Nephrology | Year: 2017
Background: Additional urinary biomarkers for diabetic nephropathy (DN) are needed, providing early and reliable diagnosis and new insights into its mechanisms. Rigorous selection criteria and homogeneous study population may improve reproducibility of the proteomic approach. Methods: Long-term type 1 diabetes patients without metabolic comorbidities were included, 11 with sustained microalbuminuria (MA) and 14 without MA (nMA). Morning urine proteins were precipitated and resolved by 2D electrophoresis. Principal component analysis (PCA) and Projection to latent structures discriminatory analysis (PLS-DA) were adopted to assess general data validity, to pick protein fractions for identification with mass spectrometry (MS), and to test predictive value of the resulting model. Results: Proteins (n = 113) detected in more than 90% patients were considered representative. Unsupervised PCA showed excellent natural data clustering without outliers. Protein spots reaching Variable Importance in Projection score above 1 in PLS (n = 42) were subjected to MS, yielding 33 positive identifications. The PLS model rebuilt with these proteins achieved accurate classification of all patients (R2X = 0.553, R2Y = 0.953, Q2 = 0.947). Thus, multiple earlier recognized biomarkers of DN were confirmed and several putative new biomarkers suggested. Among them, the highest significance was met in kininogen-1. Its activation products detected in nMA patients exceeded by an order of magnitude the amount found in MA patients. Conclusions: Reducing metabolic complexity of the diseased and control groups by meticulous patients' selection allows to focus the biomarker search in DN. Suggested new biomarkers, particularly kininogen fragments, exhibit the highest degree of correlation with MA and substantiate validation in larger and more varied cohorts. © 2017 The Author(s).
Does asymptomatic carriage of FV leiden and FII prothrombin mutations in heterozygous configuration pose an increased risk of thrombembolic complications in the course of pregnancy, labor and puerperium?
Vavrinkova B.,Charles University |
Binder T.,Charles University |
Hadacova I.,Teaching Hospital Motol |
Hrachovinova I.,Institute of Hematology and Blood Transfusion |
And 2 more authors.
Biomedical Papers | Year: 2014
Objective. To evaluate the course of pregnancy and puerperium in asymptomatic carriers of FV Leiden and FII prothrombin mutation in heterozygous configuration in terms of risk of thrombembolic disease (TED) and late pregnancy complications. To evaluate whether global prophylactic LMWH administration during pregnancy benefits these women. Methods. We monitored the incidence of thrombembolic events and severe late pregnancy complications in 473 asymptomatic carriers of FV Leiden and FII prothrombin mutation in heterozygous configuration. In 253 women, preventive LMWH application was introduced already during pregnancy. In 220 women, the application of LMWH was commenced as late as on the delivery day. In both groups application of LMWH continued during the puerperium. Results. The incidence of TED in the whole group of carriers of thrombophylic mutations accounted for 0.19%. The incidence of severe late pregnancy complications was low-2.5% compared with general population of pregnant women (6.4%). Conclusions. No direct causal relationship was established between asymptomatic carriage of Leiden and prothrombin mutation in heterozygous configuration and the occurrence of severe late pregnancy complications. There was no benefit from general LMWH prophylaxis started as early as pregnancy in these women and thus we consider it unnecessary.
Hubacek J.A.,Institute for Clinical and Experimental Medicine |
Hubacek J.A.,Center for Cardiovascular Research |
Hubacek J.A.,University of South Bohemia |
Stanek V.,Institute for Clinical and Experimental Medicine |
And 19 more authors.
Clinica Chimica Acta | Year: 2010
Background: The FTO gene plays an important role in the determination of body weight and BMI and it has been suspected of being associated with all-case mortality. Methods: We have analyzed the FTO rs17817449 variant in consecutive 1092 male patients with acute coronary syndrome (ACS) and in 1191 randomly selected Caucasian individuals (population controls). Results: The FTO variant was significantly associated with BMI both in controls (P<0.02) and ACS patients (P<0.01). In both groups, BMI was highest in GG homozygotes and lowest in TT homozygotes. There was a significant difference between the ACS patients and controls in the frequency of the FTO genotype GG (21.4% vs. 15.9%, P<0.005). FTO GG homozygotes had a significantly increased risk of ACS, compared with TT homozygotes which was independent of age and BMI (odds ratio 1.49, 95% confidence interval 1.16-1.93). The odds ratio of ACS patients for the GG genotype remained significant even after the exclusion of diabetics (100 controls and 339 ACS patients), with OR 1.32 (95% CI 1.01-1.72). Conclusions: This study provides an evidence of an association between the FTO variant and risk of ACS in Caucasian males. © 2010 Elsevier B.V.
Pitha J.,Institute for Clinical and Experimental Medicine |
Hubacek J.A.,Institute for Clinical and Experimental Medicine |
Pithova P.,Teaching Hospital Motol
Physiological Research | Year: 2010
The gene for connexin 37 (Cx37) is considered to be one of the candidate genes for cardiovascular disease. We evaluated the association between Cx37 (1019C>T) gene polymorphism (Pro319Ser) and ankle brachial blood pressure index (ABI) in women with type 1 (n=178) and type 2 (n=111) diabetes, and in women from general population (n=862). All women were genotyped for Cx37 polymorphism. In addition to traditional cardiovascular risk factors, ABI was analyzed. In women with type 1 diabetes, ABI significantly decreased from TT to CC carriers (p for trend= 0.008). A similar trend was seen in women with type 2 diabetes (p=0.050) and in women with waist circumference above 75th percentile (94 cm; n=208) of the general population (p=0.049). The gene for Cx37 was associated with subclinical atherosclerosis in women with type 1 and 2 diabetes and in women with advanced central obesity. The presence of C allele indicated increased risk. © 2010 Institute of Physiology v.v.i., Academy of Sciences of the Czech Republic.
Sramek J.,ProSpine Clinic |
Sramek J.,Czech Technical University |
Kryl J.,Teaching Hospital Motol |
Sebesta P.,Melnik Hospital
Ceska a Slovenska Neurologie a Neurochirurgie | Year: 2012
This case report describes a methodology for removal of epidural abscess located at the anterior side of spinal canal with tetraplegia AIS (ASIA - American Spinal Injury Association Impairment Scale) grade B. The abscess was first evacuated by the anterolateral Smith-Robinson approach using Caspar distractor. No other instrumentation was used. T6-T7 laminectomy and decompression was performed two weeks later to manage residual abscess. This improved motor strength to AIS grade D. MRI examination confirmed that the abscess was completely healed without postlaminectomic kyphosis. The anterior approach eliminated a risk of cervical spine kyphosis.
Dvorak C.C.,University of California at San Francisco |
Hassan A.,University College London |
Slatter M.A.,Northumbria University |
Honig M.,University of Ulm |
And 17 more authors.
Journal of Allergy and Clinical Immunology | Year: 2014
Background Patients with severe combined immunodeficiency disease who have matched sibling donors (MSDs) can proceed to hematopoietic cell transplantation (HCT) without conditioning chemotherapy. Objective We sought to determine whether the results of HCT without chemotherapy-based conditioning from matched unrelated donors (URDs), either from volunteer adults or umbilical cord blood, are comparable with those from MSDs.Methods We performed a multicenter survey of severe combined immunodeficiency transplantation centers in North America, Europe, and Australia to compile retrospective data on patients who have undergone unconditioned HCT from either URDs (n = 37) or MSDs (n = 66)Results Most patients undergoing URD HCT (92%) achieved donor T-cell engraftment compared with 97% for those with MSDs; however, estimated 5-year overall and event-free survival were worse for URD recipients (71% and 60%, respectively) compared with MSD recipients (92% and 89%, respectively; P <.01 for both). URD recipients who received pre-HCT serotherapy had similar 5-year overall survival (100%) to MSD recipients. The incidences of grade II to IV acute and chronic graft-versus-host disease were higher in URD (50% and 39%, respectively) compared with MSD (22% and 5%, respectively) recipients (P <.01 for both). In the surviving patients there was no difference in T-cell reconstitution at the last follow-up between the URD and MSD recipients; however, MSD recipients were more likely to achieve B-cell reconstitution (72% vs 17%, P <.001). Conclusion Unconditioned URD HCT achieves excellent rates of donor T-cell engraftment similar to that seen in MSD recipients, and reconstitution rates are adequate. However, only a minority will have myeloid and B-cell reconstitution, and attention must be paid to graft-versus-host disease prophylaxis. This approach might be safer in children ineligible for intense regimens to spare the potential complications of chemotherapy. © 2014 American Academy of Allergy, Asthma and Immunology.
Pitha J.,Institute for Clinical and Experimental Medicine |
Pithova P.,Teaching Hospital Motol |
Hubacek J.A.,Institute for Clinical and Experimental Medicine
Biopolymers and Cell | Year: 2011
In spite of the strong prognostic value of all traditional cardiovascular risk factors, still striking differences exist in the prevalence of clinical events between patients at apparently similar risk. One of the main reasons is different genetic background. One of recently discussed candidate genes for cardiovascular disease is the gene for the protein Connexin 37 (Cx37). This protein is a part of gap junctions responsible for communications between cells including cells in the vessel wall. Studies focused on the association between Cx37 gene polymorphism (1019C > T; Pro319Ser) and cardiovascular disease demonstrate inconsistent results. Our findings in 1.316 men and women indicated that the Cx37 gene polymorphism (genotype CC) is significantly associated with acute coronary syndrome in non-smoking women. In addition, in urban and rural women from general population (n = 1.056) with impaired fasting glycaemia the same genotype is associated with increased intima media thickness of carotid arteries measured by ultrasound. Finally, in 289 women with diabetes type 1 or 2, and in 208 women from general population with central obesity, the CC genotype was associated with lower ankle brachial blood pressure index. These data indicate that Cx37 gene polymorphism could have gender- and smoking- dependent effects on acute coronary events and glucose dependent effect on atherosclerosis in women. © Institute of Molecular Biology and Genetics NAS of Ukraine, 2011.
Foltan R.,Charles University |
Hoffmannova J.,Charles University |
Pavlikova G.,Charles University |
Hanzelka T.,Charles University |
And 5 more authors.
International Journal of Oral and Maxillofacial Surgery | Year: 2011
Orthognathic surgery has varying effects on respiratory parameters. The authors undertook a prospective study of patients requiring mandibular advancement, mandibular setback and maxillary Le Fort I advancement, and surgically assisted rapid maxillary expansion (SARME). Breathing parameters were monitored in a sleep laboratory the night before the operation and in a mean of 9.5 months after the operation. In patients treated with mandibular advancement, the respiratory disturbance index (RDI), oxygen desaturation index (ODI), and number of obstructive apnoeas (OAs) improved significantly. In patients treated with mandibular setback and maxillary Le Fort I advancement, the RDI, ODI, index of flow limitations (IFL), number of obstructive hypopnoeas (OHs), OA, and oxygen saturation deteriorated. In contrast, patients treated with SARME improved only mildly. These results indicate that bimaxillary surgery for Class III malocclusion increased upper airway resistance, probably because of a more dorsal positioning of the base of the tongue, representing an iatrogenic obstructive sleep apnoea (OSA). A young person would probably be able to balance such a decline in respiratory function using different adaptative mechanisms. Mandibular advancement significantly improved respiratory parameters during sleep. The possible effect of orthognathic surgery on the upper airways should be incorporated into the treatment plan. © 2010 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Vlcek M.,Teaching Hospital Motol |
Jaganjac E.,Teaching Hospital Motol |
Pech J.,Teaching Hospital Motol |
Jonas D.,Teaching Hospital Motol |
Kebrle R.,Institute for Hand and Plastic Surgery Vysoke nad Jizerou
Bosnian journal of basic medical sciences / Udruženje basičnih mediciniskih znanosti = Association of Basic Medical Sciences | Year: 2014
PURPOSE OF THE STUDY: Can minimally invasive intramedullary osteosynthesis of distal radius fractures provide better therapeutic results than multidirectional locking plates. Retrospective study of 68 patients operated for distal radius fractures, 18 were treated with intramedullary X-screw (XSCR) fixation and 50 with the multidirectional angle-stable plate system (APTUS). The evaluation at 1-year follow-up included functional status of the wrist and hand, and radiographic findings. In the XSCR group, the functional outcomes of the treated extremity did not achieve values comparable with those of the uninjured side in any of the parameters measured. The radiographic findings did not meet the requirements of successful healing due to failure to restore an anatomical volar tilt in 22.2% cases. In the APTUS group, comparable values of the injured and the uninjured side were achieved in radial deviation, ulnar deviation, pronation, supination and grip strength. The radiographic criteria of successful healing were met by all fractures treated by locking plate osteosynthesis. Implant migration associated with secondary displacement of bone fragments was recorded in 33.3 % of the XSCR patients and only in 4.0 % of the APTUS patients. The overall evaluation show that intramedullary osteosynthesis does not produce better treatment outcomes compared with plate osteosynthesis in indicated types of fractures.
PubMed | University of Michigan, Harvard University, Dana-Farber Cancer Institute, Teaching Hospital Motol and 13 more.
Type: Comparative Study | Journal: The Journal of allergy and clinical immunology | Year: 2014
Patients with severe combined immunodeficiency disease who have matched sibling donors (MSDs) can proceed to hematopoietic cell transplantation (HCT) without conditioning chemotherapy.We sought to determine whether the results of HCT without chemotherapy-based conditioning from matched unrelated donors (URDs), either from volunteer adults or umbilical cord blood, are comparable with those from MSDs.We performed a multicenter survey of severe combined immunodeficiency transplantation centers in North America, Europe, and Australia to compile retrospective data on patients who have undergone unconditioned HCT from either URDs (n = 37) or MSDs (n = 66).Most patients undergoing URD HCT (92%) achieved donor T-cell engraftment compared with 97% for those with MSDs; however, estimated 5-year overall and event-free survival were worse for URD recipients (71% and 60%, respectively) compared with MSD recipients (92% and 89%, respectively; P < .01 for both). URD recipients who received pre-HCT serotherapy had similar 5-year overall survival (100%) to MSD recipients. The incidences of grade II to IV acute and chronic graft-versus-host disease were higher in URD (50% and 39%, respectively) compared with MSD (22% and 5%, respectively) recipients (P < .01 for both). In the surviving patients there was no difference in T-cell reconstitution at the last follow-up between the URD and MSD recipients; however, MSD recipients were more likely to achieve B-cell reconstitution (72% vs 17%, P < .001).Unconditioned URD HCT achieves excellent rates of donor T-cell engraftment similar to that seen in MSD recipients, and reconstitution rates are adequate. However, only a minority will have myeloid and B-cell reconstitution, and attention must be paid to graft-versus-host disease prophylaxis. This approach might be safer in children ineligible for intense regimens to spare the potential complications of chemotherapy.