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Aims: The Y chromosome accumulates male-related genes including sex-determining region of Y-chromosome (SRY) and several spermatogenesis-related genes. The long arm contains azoospermia factor (AZF) region (including sub-regions AZFa, AZFb and AZFc). Microdeletions in this region are responsible for azoospermia and oligospermia and result in the male infertility. The aim of this study was to analyze incidence of microdeletions in the AZF region of Y chromosome in patients with azoospermia from Slovakia. Patients and Methods: Over the period from 2005 to 2009 a total of 239 men (mean age 31.74 years) were analyzed. The diagnosis of azoospermia was established on the basis of semen analysis. All patient samples were analyzed cytogenetically. Chromosomal analysis was performed on all patients on cultured lymphocytes from peripheral blood. For exact diagnosis of microdeletions in AZF region we used a PCR-method using a set of sequence-tagged sites from all AZF sub-regions (according to the recommendation by the European Academy of Andrology and the European Quality Monitoring Network Group). Results: Among our 226 patients with azoospermia and with normal karyotype, 8 patients (mean age 30.6 years) had microdeletions in the AZF region of the Y chromosome (3.35%). Considering particular types of deletions we determined deletions in each region AZFa,b,c but also a complete deletion of the entire AZF region. The presence of microdeletion(s) in the AZFc region was the most frequent. In our study we found 12 patients (5%) with 47,XXY karyotype (Klinefelter syndrome), but these patients didn't have microdeletion of Y chromosomes. Conclusion: The study confirmed that percentage of microdeletions in the AZF region is low in Slovak azoospermic patients, but important from a prognostic view.

This Supplement to the BIOMEDICAL PAPERS, Volume 150 (Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub), is devoted to the 33rd Congress of the Czech Society of Pathologists and the 2nd Satelite Symposium & Workshop on Molecular Pathology held at the Regional Centre Olomouc & Faculty of Medicine, Palacký University Olomouc, May 4–6, 2006.

Introduction: According to recent findings, certain clinical symptoms of patients suffering from affective and anxiety disorder can be related to dissociation. The aim of our study was to examine if the level of dissociation in bipolar affective disorder differed from the level of dissociation in healthy volunteers. Methods: 41 patients suffering from bipolar disorder (51.2% females), and 198 healthy controls ( 71.2% females) were included in the study. The patients with bipolar affective disorder in remission were recruited from the Outpatient department of the Department of Psychiatry of the University Hospital Olomouc. They were psychiatrically assessed and the state of the disorder was evaluated by an experienced psychiatrist. Only patients in remission, evaluated as 1 or 2 points of clinical global impression - severity scale, were included in the study. All participants were assessed with the Dissociative Experiences Scale (DES). Results: There were no differences in the two groups in demographic variables like age, gender and education. Patients had a significantly higher mean score on the DES and pathological DES than healthy controls. Conclusion: Our results suggest that the level of psychological dissociation in bipolar affective patients is higher than in healthy controls.

Background: Studies have shown that oxidative stress increases with increasing human age. Protein carbonyl accumulation is an indicator of oxidative damage to proteins during aging in cells and tissues. The present study is focused on the relationship between human age and protein oxidation in erythrocyte membranes in a healthy Indian population. Materials and Methods: The sample included healthy human subjects (n = 49) between the ages of 17 to 80 years. Their blood was collected and assayed spectrophotometrically for oxidative protein damage in terms of protein carbonyls and plasma antioxidant capacity in terms of FRAP. Results: Protein carbonyl content was found to increase in an age-related pattern indicating an increase in oxidative protein damage in older subjects (p <0.0001, r = 0.8269). There was also a significant negative correlation between protein oxidation and plasma antioxidant capacity measured in terms of ferric reducing antioxidant potential (FRAP) values (p<0.0001; r = -0.8695). Conclusion: Our results substantiate the occurrence of oxidative stress during human aging. Elevated erythrocyte membrane carbonyl levels found with increasing age in this study may be viewed as a biomarker for aging.

Aims: This study compares the outcomes of patients with high-risk acute myeloid leukemia (AML) who underwent allogeneic stem cell transplantation (SCT) after conditioning combining busulfan (16 mg/kg orally) and cyclophosphamide (120 mg/kg intravenously) (BU-CY) with those allografted after administration of fludarabine (150 mg/m² intravenously), busulfan (12 mg/kg orally) and thymoglobulin (6 mg/kg intravenously) (FLU-BU12-TG). Material and methods: SCT after BU-CY and FLU-BU12-TG was performed in 21 and 10 AML patients. There were no significant differences between groups in number of patients treated in complete disease remission, gender, age, donors, CD34+, mononuclear cell (MNC) count in the graft and follow-up period. However, significantly more SCTs from unrelated (90% vs. 19%; p=0.00018) and HLA-mismatched donors (50% vs. 0%; p=0.0004) were performed in the FLU-BU12-TG group. The Cox proportional hazards model was used to assess the risk of post-transplant AML relapse and non-relapse mortality (NRM). The probability of post-transplant 2-year event-free survival (EFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Results: No significant differences were found between the FLU-BU12-TG and BU-CY groups in risk of AML relapse (HR=1.036; 95% CI [0.102 - 10.47]; p=0.9), post-transplant NRM (HR=0.25; 95% CI [0.031 - 1.96]; p=0.18), 2-year EFS (89% vs. 43%; p=0.19) or OS (79% vs. 57%; p=0.23). Conclusion: These pilot results demonstrate the efficacy of the new FLU-BU12-TG conditioning regimen in patients allografted for high-risk AML. This conditioning might become an alternative approach in patients at high risk of severe post-transplant complications after the standard BU-CY myeloablative regimen.

Aim: This is a case report of a 51 year old male with marked splenomegaly, basophilia, severe thrombocytopenia, anemia and high SFKL phosphorylation downstream of Bcr-Abl, investigated for association of the e6a2 BCR-ABL fusion gene and marked basophilia. The treatment strategy implications in patients with Philadelphia positive CML are described. Methods: RT-PCR and sequencing were carried out on the peripheral blood leukocytes to detect the type of BCR-ABL transcript. The BCR-ABL mutational status was assessed using sequencing of the RT-PCR products. The in vitro test of sensitivity to TKIs was based on detecting inhibited phosphorylation of the Crkl and Phospho-Src family kinases (SFK, Tyr416) using immunodetection. Results: The cytogenetics revealed 90% of Ph+ (Philadelphia) cells in the bone marrow aspirate with no additional clonal chromosomal abnormalities at diagnosis. This correlated with an accelerated phase of the CML. Sequencing analysis of reverse transcribed and PCR amplified BCR-ABL transcript revealed a rare e6a2 fusion, with no evidence for Bcr-Abl kinase domain mutation. Western blot analysis showed high phosphorylation (activation) of Crkl and the Src family of kinases (P-SFK). In vitro test of sensitivity of the patients' leukemic cells to imatinib demonstrated sensitivity of Bcr-Abl tyrosine kinase to imatinib, as assessed by a decrease in phosphorylated Crkl and the disappearance of P-SFK, suggesting that P-Src reflects only the Bcr-Abl-dependent Src activity. The initial treatment strategy was reduced imatinib and search for an unrelated hematopoietic stem cell donor (according to the ELN recommendations). The patient was allografted with peripheral stem cells from an HLA- identical male donor but on day +70 graft failure occurred. He was allografted again with the peripheral stem cells from an HLA-identical female donor, engrafted on day +15 and showed 100% donor chimerism with no evidence of the e6a2 BCR-ABL fusion transcript on day +30. Conclusion: The clinical disease course in patients with the rare e6a2 BCR-ABL transcript variant is aggressive. This may be the result of increased kinase activity due to partial loss of the guanine exchange factor/dbl-like domain which mediates the interaction with several Ras-like G-proteins involved in cell proliferation, signal transduction, and cytoskeletal organization. For the above reasons, these patients should receive stem cell transplant immediately after a short course of treatment with imatinib/ dual Src/Abl kinase inhibitor or they should be registered in clinical trials with experimental agents.

Introduction: Adiponectin is adipocytokin with anti-inflammatory and anti-atherogenic effects. However, studies examining the relationship between adiponectin and cardiovascular diseases have shown inconsistent results. Aims: The aim of this study was to evaluate the plasma levels of adiponectin in clinically asymptomatic subjects with various dyslipidemic phenotypes. The associations between adiponectin and risk factors for atherosclerosis, markers of insulin resistance, and the intima-media thickness of the common carotid artery (IMT) were also evaluated. Methods: 234 asymptomatic subjects were divided into four dyslipidemic phenotypes (DLP) according to apolipoprotein B (apoB) and triglycerides (TG): DLP1 (n=58, apoB<1.2 g/l and TG<1.5 mmol/l), DLP2 (n=47, apoB<1.2 g/l and TG≥1.5 mmol/l), DLP3 (n=31, apoB≥1.2 g/l and TG<1.5 mmol/l) and DLP4 (n=98, apoB≥1.2 g/l and TG≥1.5 mmol/l). DLP1 (normo-apoB/normo-TG) served as a control group. Results: Significant differences in adiponectin levels between normolipidemic phenotype - DLP1 (16.1[10.3-20.8] mg/l) and hypertriglyceridemic phenotypes - DLP2 (9.5[6.8-13.0] mg/l, p<0.01) and DLP4 (10.1[7.4-16.8] mg/l, p<0.01) after adjustment for age, sex and body mass index were found. Adiponectin correlated positively with highdensity lipoprotein cholesterol and apolipoprotein A1 (apoA1), negatively with triglycerides, apoB/apoA1, highsensitivity C-reactive protein, insulin, homeostasis model assessment and waist circumference. ApoA1 and insulin were detected as independent predictors for adiponectin levels in multivariate regression analysis. Adiponectin did not correlate with IMT. Conclusions: Individuals with hypertriglyceridemic phenotypes showed decreased adiponectin levels in comparison with normolipidemic subjects. Adiponectin was associated with lipid parameters, markers of insulin resistance, chronic inflammation and visceral obesity. But no association between adiponectin and IMT was found.

Aims: To compare the pharmacodynamics of 0.6 mg kg^-1 rocuronium in young and older patients of both genders during total intravenous anesthesia. Methods: Following local ethics committee approval and informed consent, patients scheduled for surgery under total intravenous anesthesia (propofol/sufentanil) were divided into 4 study groups: 37 males aged 20-40, 40 males aged 60-75 yrs, 43 females aged 20-40 and 38 females aged 60-75 yrs. Neuromuscular block following rocuronium (0.6 mg kg^-1) was monitored: train-of-four [TOF] stimulation of the ulnar nerve at 15-s intervals, EMG of the adductor pollicis muscle. The onset time (from application of rocuronium to maximum depression of T₁), clinical duration (from application to 25% recovery of T₁), and time to full spontaneous recovery (from application to TOF-ratio ≥ 0.9) were determined for each patient. The Kruskal-Wallis test was used to compare differences between groups; P<0.05 was considered statistically significant. Results: The onset time (median [interquartile range]) in the respective groups was 90 [80-110]^BCD, 135 [116-165]^AC, 75 [60-90]^ABD, and 120 [90-146]^AC seconds. The clinical duration was 30 [25-42]^BCD, 58 [53-67]^AD, 50 [40-65]^AD, and 85 [70-90]^ABC min. Interval to full spontaneous recovery was 59 [51-67]^BCD, 102 [75-106]^A, 76 [66-91]^AD, and 128 [94-137]^AC min. (^AP<0.05 vs. young males, ^BP<0.05 vs. elderly males, ^CP<0.05 vs. young females, ^DP<0.05 vs. elderly females). Conclusion: Females and older patients were more sensitive to rocuronium.

Aim: A case report of subacute effusive-constrictive pericarditis in a patient with iatrogenic hemopericardium is presented. Methods: A 69-year-old man was referred to our department for percutaneous coronary intervention complicated with hemopericardium with cardiac tamponade. Continuous bleeding after pericardiocentesis required an urgent surgical revision with evacuation of hemopericardium and local treatment of the sources of bleeding. A mild to moderate pericardial effusion persisted in the post-operative period, without any symptoms of cardiac tamponade. A global heart failure developed in the patient eleven months after complicated coronary intervention (surgical revision). A technically successful pericardiocentesis did not improve the clinical state of the patient. Echocardiography and magnetic resonance imaging confirmed the diagnosis of effusive-constrictive pericarditis. Results: Subsequent pericardiectomy resulted in a prompt and complete relief of symptoms and signs of heart failure. Conclusion: Effusive-constrictive pericarditis is an uncommon disorder characterised by symptoms of refractory cardiac failure, thickening of the visceral pericardium and pericardial effusion, with no improvement after pericardiocentesis. In indicated cases, pericadiectomy leads to recovery in a large percentage of patients.

Background: This prospective study aimed at assessing the effect of initial antibiotic therapy on the mortality of patients with hospital-acquired pneumonia (HAP) by analyzing bacterial pathogens and their resistance to antimicrobial agents. Methods: Included were patients hospitalized in the Department of Anesthesiology and Intensive Care Medicine, Faculty of Medicine and Dentistry, Palacký University Olomouc and University Hospital Olomouc in 2009 who developed HAP. Bacterial pathogens and their resistance to antibiotics were identified using standard microbiological methods. The patient's mortality with respect to their initial antibiotic therapy was statistically analyzed. Results: The group comprised 51 patients with HAP. Early-onset HAP was identified in 7 (14%) patients and late-onset HAP in 44 (86%) patients. The most frequent bacterial pathogens were strains of Klebsiella pneumoniae, Pseudomonas aeruginosa, Burkholderia cepacia complex and Escherichia coli, together accounting for 72%. Eighteen patients died directly due to HAP, an overall mortality rate of 35%. If initial therapy effective against the bacterial pathogen was selected, 21 patients survived and 9 died. If the bacterial pathogens were resistant to the selected initial antibiotic therapy, 9 patients died and 12 survived. Conclusions: The mortality rates were 30% and 43% for adequate and inadequate antibiotic therapy, respectively. Given the small group of patients, the difference has low statistical significance. However, it does document the clinical impact of bacterial resistance on the survival or death of patients with HAP.

Background: Dental implants are a suitable option for the replacement of some or all missing teeth. Their main function is to secure the stability of the artificial tooth. The implant material interacts with several cell types including osteoblasts, gingival fibroblasts, periodontal ligament fibroblasts and monocytes. The most common material used is pure titanium which is corrosion resistant and has an elasticity modulus similar to that of bone. In recent years, diverse modified titanium surfaces have also been developed. The wound healing around the implant is a complex process that determines how well the host can heal and accept the implanted material. For this reason, search for markers of the biocompatibility of these new materials is paramount. To identify markers found to be suitable for studying the biocompatibility of dental implants. Methods: Review of Pubmed and Web of Science databases for the years 1958-2010. Conclusions: The surface of dental implant material should enhance firm attachment of the implant to junctional epithelium, soft connective tissue and bone. For the purposes of dental implant biocompatibility studies, a number of markers produced by osteoblasts or by cells of periodontal ligament have been proposed. In general, the most typical markers for osteoblasts and fibroblasts are alkaline phosphatase and collagen I, respectively. The involvement of both cell types in the inflammatory response is primarily evaluated by determination of tumour necrosis factor α and proinflammatory interleukins.

Aim: Provide an overview of how bipolar disorder affects cognitive function in patients. Methods: MEDLINE and PsycInfo data bases were searched for articles indexed by the combinations of MESH term or key word "bipolar disorder" with the following terms: "cognition", "memory", "neuropsychology", "neuropsychological tests", "lithium", "anticonvulsants", "antipsychotics", and "schizophrenia". Constraints limiting time period of publications or their language were not applied. Reference lists of publications identified by these procedures were hand-searched for additional relevant citations. Results: There is evidence of stable and lasting cognitive impairment in all phases of bipolar disorder, including the remission phase, particularly in the following domains: sustained attention, memory and executive functions. But research on the cognitive functions has yielded inconsistent results over recent years. There is a growing need for clarification regarding the magnitude, clinical relevance and confounding variables of cognitive impairment in bipolar patients. The impact of bipolar illness on cognition can be influenced by age of onset, pharmacological treatments, individual response, familial risk factors, and clinical features. In addition to the mood state, cognitive performance in bipolar patients is influenced by seasonality. Conclusion: Previous optimistic assumptions about the prognosis of bipolar disorder were based on the success of the control of mood symptoms by pharmacotherapy. However, it is now clear that the "remitted" euthymic bipolar patients have distinct impairments of executive function, verbal memory, psychomotor speed, and sustained attention. Mood stabilizers and atypical antipsychotics may reduce cognitive deficits in certain domains and may have a positive effect on quality of life and social functioning.

Background: In complex therapeutic algorithms for cancer, regional intra-arterial chemotherapy is usually used as an adjuvant and placed in the beginning of treatment. Clinical experience however shows that the achieved remission of malignant tumour illness after non-adjuvant chemotherapy is only temporary and short-lived. The illness progresses relatively quickly if the patient receives no further treatment and most clinical studies have not found any significant increase in life expectancy in oncological patients treated with this method. The question remains to what extent the poor results are due to the treatment method and its position in the therapeutic algorithm, and to what extent they are due to imperfect knowledge of molecular tumour genetics or inappropriate choice of the neoadjuvant intra-arterial chemotherapy Methods: We compared preliminary results of immunohistochemical examinations (detection and analysis of expression of proteins Ku 70, STAT 1,3,5 which take part in the regulation of cell cycle apoptosis and repair of damaged DNA, carried out before and after chemotherapy, suggest that depending on the effects of neoadjuvant intra-arterial chemotherapy and patient's survivance. Results and Conclusion: An overview of intra-arterial neoadjuvant chemotherapy of head and neck is presented. Knowledge of cell cycle processes, especialy apoptosis and repair of damaged DNA, could significantly influence the choice of the therapeutic algorithm and therapeutical effect.

Background: The autogenous brachiocefalic or brachiobasilic arteriovenous elbow fistula is not considered to be only the secondary haemodialysis access. In patients with an unsuitable forearm vessel bundle, it is indicated as primary access and it is the method preferred to the fistula creation using a vascular prosthesis. Its rather rare complication is the development of upper extremity ischemia. Aim: To summarise current knowledge of this fistula type and its associated complications Methods: Review of the literature. Results: The creation and maturation of the fistula and occurrence of the steal syndrome is infl uenced by a number of factors. The analysis and awareness of such factors will provide for creation of a suitable fistula as well as for timely complication diagnostics and treatment. Conclusions: The autogenous elbow fistula utilising the brachial artery and the cephalic or basilic vein in the upper extremity represents a high-quality haemodialysis access. Its potential complication is the occurrence of the steal syndrome. Its occurrence and manifestations do not constitute indications for ligation of the access. The gathered information shows that a suitable surgical procedure can help meet the basic rule for haemodialysis access - resolving the ischemia and maintaining the access.

Background: Adenine and adenosine-acting aminohydrolases are important groups of enzymes responsible for the metabolic salvage of purine compounds. Several subclasses of these enzymes have been described and given current knowledge of the full genome sequences of many organisms, it is possible to identify genes encoding these enzymes and group them according to their primary structure. Methods and Results: This article is a short overview of the enzymes classified as adenine and adenosine deaminase. It summarises knowledge of their occurrence, genetic basis and their catalytic and structural properties. Conclusions: These enzymes are constitutive components of purine metabolism and their impairment may cause serious medical disorders. In humans, adenosine deaminase deficiency is linked to severe combined immunodeficiency and as such the enzyme has been approved for the first gene therapy trial. The role of these enzymes in plants is unclear, since the activity was has not been detected in extracts and putative genes have not been yet cloned and analyzed. A literature search and amino acid identity comparison show that Ascomycetes contain only adenine deaminase, but not adenosine deaminase, despite the fact that corresponding genes are annotated in databases as the adenosine cleaving enzymes because they share the same conserved domain.

Background: Borrelia burgdorferi sensu lato is a group of at least twelve closely related species some of which are responsible for Lyme disease, the most frequent zoonosis in Europe and the USA. Many of the biological features of Borrelia are unique in prokaryotes and very interesting not only from the medical viewpoint but also from the view of molecular biology. Methods: Relevant recent articles were searched using PubMed and Google search tools. Results and Conclusion: This is a review of the biological, genetic and physiological features of the spirochete species group, Borrelia burgdorferi sensu lato. In spite of a lot of recent articles focused on B. burgdorferi sensu lato, many features of Borrelia biology remain obscure. It is one of the main reasons for persisting problems with prevention, diagnosis and therapy of Lyme disease. The aim of the review is to summarize ongoing current knowledge into a lucid and comprehensible form.

Over more than 20 years hair analysis for drugs has been gaining increasing attention and recognition in various toxicological fields as preemployment and employment screening, forensic sciences, doping control of banned substances, clinical diagnostics in health problems. Hair analysis for drugs can expand the toxicological examination of conventional materials and thus contribute with additional important information to the complex evaluation of a certain case. Hair is a unique material for the retrospective investigation of chronic drug consumption, intentional or unintentional chronic poisoning in criminal cases, gestational drug exposure or environmental exposure to pollutants and adulterants and with specific ultrasensitive procedures allow to demonstrate even a previous single dose administration in a very low amount. Assuming the ideal hair steady and uniform growth, segmental hair analysis can provide the information about the time course of the substance use or exposure. However, the physiological background of hair growth, mechanisms of drug incorporation are not simple, not yet understood in full details and need not be evaluated exactly in all cases. The hair sampling, storage, sample preparation, analytical performance themselves are also very important for final results. Different laboratory attitudes can produce different results. The full information on circumstances of the case examined must be taken into account during interpretation. The pitfalls in hair analysis should be known and avoided to assure the responsible and correct interpretation of laboratory results adequate to an individual case.

Objective: Clinical observations and mathematical models show that dental implants are influenced by the magnitude of loading. Therefore, the knowledge of mandible movement during mastication is important to assess occlusal and masticatory force vectors. The purpose of this study was to detect the path of movement of the lower jaw and to distinguish stages of mastication, duration of bolus processing and peak amplitude of mastication. Method: Motion analysis was used to record three-dimensional mandible movements. Individualized sensors were rigidly attached to the mandible of 51 study participants. At the beginning of the measurement, all subjects were asked to move the mandible in extreme positions (maximal opening and maximal lateral movements). Then, each subject masticated a bite of hard and soft food. Duration of bolus mastication and peak amplitude of mastication movement in mesio-distal, cranio-caudal and vestibulo-oral axes related to peak amplitude of marginal movements were evaluated for each subject. The chewing record of each subject was divided into three phases (chopping, grinding and swallowing), and the duration of mastication and number of closing movements were evaluated. Results: The findings of this pilot study suggest that masticatory movements vary in individuals. Bolus character influences the process duration, but not the frequency of closing movements. Neither gender nor age had any influence on either the time or frequency of bolus processing. Conclusion: Relationships to directions and magnitudes of acting chewing force should be more precisely examined since transversally acted forces during grinding are important factors in tooth/implant overloading.

Background: The number of medical undergraduates taking part in Student Scientific Activities (SSA) at Jessenius Faculty of Medicine Comenius University in Slovakia remains low. The aim of this study was to discover some of the factors responsible and suggest improvements. Methods: An anonymous 30-item questionnaire was devised and sent to 245 medical undergraduates (UG) of the 1st, 2nd, 3rd and 5th years. Results: Foreign fellowships, postgraduate research, assistant posts at universities and financial incentives were cited as the main positive motivators for participation in UG student scientific research. Characteristics in tutors that encouraged student research were scientific knowledge, giving time to students and enthusiasm for research while poor infrastructure, tutor lack of time/interest, own time constraints, weak career motivation and lack of information were the strongest discouraging factors. Conclusion: Involvement of students in SSA is infl uenced by many factors. To increase the number of students taking part in SSA, student research and/or continuing to Ph.D and scientific career, these factors need to be addressed by medical schools.

Background: The introduction of the calcineurin inhibitors (CI) cyclosporine and tacrolimus into immunosuppressive protocols initiated a new era in organ transplantation with excellent short-term graft survival. Nevertheless, the chronic nephrotoxicity of these drugs represents a significant adverse factor limiting their long-term use. Patients treated with a CI can be at risk for developing renal failure and this problem is especially pronounced in patients after renal transplantation. Methods and Results: In a review paper we summarize the clinical aspects, histological manifestations and pitfalls of diagnostics of acute and chronic CI nephrotoxicity in patients after kidney transplantation. We look in detail at the disputed relationship between blood concentrations of cyclosporine and tacrolimus and histological manifestation of toxicity and summarize data showing that for toxic effects, local renal exposure to CI and their metabolites can play a more significant role than systemic exposure. We also include recent views on the pathophysiologic and molecular mechanisms underlying these changes; factors influencing local susceptibility to CI nephrotoxicity are discussed, including variability of expression and activity of P-glycoprotein and cytochrome P450. Last but not least we summarize our own experience with clinically manifest and subclinical forms of nephrotoxicity and their impact on the progression of chronic graft changes. Conclusions: Owing to their unique effects, CI remain the cornerstone of most immunosuppressive protocols for renal transplantation. Together with optimization of local kidney exposure to CI and their metabolites, efforts to reduce systemic levels as much as possible are the most important preventive measure for reducing toxic renal graft damage.

Backround. Despite holistic approach to psychosomatic medicine, gastroenterological disorders (GI) tend to be categorized broadly into "functional" and "organic". Major GI illnesses are Inflammatory bowel diseases (IBD) include ulcerative colitis and Crohn's disease. Both are chronic, with remissions and relapses over the years while irritable bowel syndrome (IBS) is a common, often disabling functional gastrointestinal disorder. Methods: A literature review was performed using the National Library of Medicine PubMed database, including all resources within the period 1991-2008, additional references were found through bibliography reviews of relevant articles. Results: Psychological problems: Higher scores of neuroticism, depression, inhibition, and emotional instability, are typical for many patients with chronic diseases and nonspecific for chronic gastroenterological disorders. Patients with chronic gastrointestinal disorders have impaired health-related quality. Psychological treatments: There have been few adequate psychological treatment trials in IBD. These achieved lower demands for health care rather than a reduction of anxiety or depression. Psychotherapy with chronic gastrointestinal disorders could lead to improve the course of the disease, changing psychological factors such as depression and dysfunctional coping and improving the patient's quality of life. Conclusions: There seem to be "risk patients" in whom psychosocial components have a bigger influence on the course of disease than in other patients; and those would probably benefit from psychotherapeutic treatment. Psychological treatments help patients manage the psychological distress which worsens bowel symptoms and quality of life.

Introduction: The presence of a velocity in isovolumic contraction phase (Vivc) evaluated using tissue Pulse wave Doppler myocardial imaging (PWDMI) correlates with a transmural extent of scar after myocardial infarction. The possible clinical usefulness of Vivc evaluated using color Doppler myocardial imaging (CDMI) in detection of a scar after myocardial infarction extent in patients with coronary heart disease (CHD) and low LV systolic function remains to be clarified. Patients and methods: 57 patients with CHD (average LVEF 33.5±5%), examined echocardiographicaly (17-segment LV model, 689 segments evaluated) and by cardiac magnetic resonance. All segments were scanned for Vivc presence using CDMI. Vivc presence/absence was correlated with signs of a scar after MI in all segments and in akinetic segments separately. Results: We found significantly larger values of wall thickness (8.2±2,2 vs. 7.1±1.9, p<0.0001), significantly lower values of average late enhancement (LE) extent (1.32±1.78 vs. 1.66±1.98, p=0.041) and LE/wall thickness ratio (20.1±29.8 vs. 29.6±36.7, p=0.008) in segments with present Vivc. Vivc presence in a segment with an abnormal wall motion had a sensitivity of 72.9% and a specificity of 35.7% in recognizing a segment without a transmural scar (LE/ wall thickness ratio ≤75%). Vivc absence in a segment with an abnormal wall motion had a sensitivity of 72.7% and a specificity of 41.2% in recognizing a segment with a transmural scar (LE/wall thickness ratio ≥75%). Conclusions: Isovolumic velocities evaluation assessed using color Doppler myocardial imaging is not applicable in a real-world clinical setting. The presence or absence of a velocity pattern during LV isovolumic contraction is not useful in in the assessment of a post-infarction scar transmurality.

Background: Despite the introduction of anti-D prophylaxis into clinical practice, RhD alloimmunization still presents a problem to date. The actual incidence of RhD alloimmunization in pregnant women remains unknown in most countries. Anti-D immunoglobulin is administered to RhD negative women at a fixed dose and in much greater amounts than is actually necessary. On the other hand, it is not possible to diagnose cases where greater doses are needed. To optimize the prevention of RhD alloimmunization in RhD negative women, it is important to diagnose conditions that lead to fetomaternal hemorrhage (FMH), precisely determine the volume and subsequently administer the appropriate dose of anti-D immunoglobulin. The possibility to accurately detect FMH and precisely determine its volume would enable more effective and less costly prevention of RhD alloimmunization. Anti-D immunoglobulin could be administered only in indicated cases and only in doses essentially necessary for prevention of RhD alloimmunization. Methods and results: The Cochrane and UpToDate databases of systematic reviews, as well as national guidelines, were reviewed. Conclusions: Due to the medical significance and indispensable economic costs associated with prevention of RhD alloimmunization, it would be appropriate to establish exact methodical guidelines. The text itself should be limited to a list of potentially sensitising events during which anti-D immunoglobulin should be administered to RhD negative women if anti-D antibodies are not already present. Following each potentially sensitising event, the minimal dose of anti-D immunoglobulin necessary for prevention of RhD alloimmunization should be determined. After 20 weeks of gestation, the volume of FMH should also be determined to specify the necessary dose of anti-D immunoglobulin.

Aims: No effective treatment for lung cancer exists currently. One reason for this, is the development of drug resistance, assumed to be associated with cancer stem cell (CSCs) emergence within the tumour. This pilot study aimed to identify CSCs in 121 non-small cell lung cancer (NSCLC) patient samples via detection of the expression of stem cell markers - CD133 and nestin. Material and methods: Archived paraffin blocks of 121 patient samples were prepared as Tissue Microarrays (TMA). Indirect immunohistochemical staining was used to determine the level of expression of CD133 and nestin. Double immunofluorescence staining was used to investigate the co-expression of these two markers. To determine the correlation between expression of nestin and CD133 with the length of asymptomatic period and overall patient survival we used the Kaplan-Meyer analysis. Results: CD133 expression was detected in 22 (19%), nestin in the epithelium in 74 (66%) and vasculature in 78 (70%) of patients. Co-expression of these two markers was found in 21 (17%) patients in less than 1% of positive cells without impact on disease free or overall survival. Conclusions: We identified CD133⁺/nestin⁺ cells as novel potential markers of lung cancer CSCs.

Aims: To provide the first single-center study of a Czech renal transplant program that compares skin cancer risk estimates to the general population. Methods: We studied a total of 603 patients undergoing renal transplantation at the University Hospital Olomouc Transplant Center between January 1984 and December 2009. The mean time of follow-up was 5.5 years. Three patients were excluded for skin cancer diagnosis before transplant. The cohort was linked with the National Cancer Registry of the Czech Republic. For non-melanoma skin cancer (NMSC), the observed number of cancers were compared to the expected numbers of NMSC based on national cancer incidence rates stratified by age. The standartized incidence ratio (SIR) was calculated as observed-to-expected ratios. Results: We found a total of 127 cases of skin cancers in 55 patients. 52/55 (94.5%) were patients with non-melanoma skin cancers, 2/55 (3.6%) patients had malignant melanoma, and we uncovered one case of merkel cell carcinoma of the skin (1.8%). There were no cases of Kaposi's sarcoma, cutaneous lymphoma or malignant fibrous histiocytoma. For NMSC, the overall SIR was 7.39 (95% confidence interval 5.52-9.70). Thus, skin cancer was the most common malignant condition, representing 64.1% of all malignant tumours detected in study population. Conclusion: We confirmed that skin cancer is a major complication in renal transplant recipients. Therefore it is important to increase the intensity of surveillence for these lesions in transplant patients.

Introduction: The cerebellum is a very complex structure with many motor/non-motor functions and direct and indirect connections with almost the entire central nervous system. Transcranial magnetic stimulation (TMS) is a non-invasive electrophysiological method for studying, diagnosing, and treating disorders of the nervous system. The aim of the present review is to summarise the research and potential clinical uses of cerebellar TMS. Methods: PubMed literature search using the key words "cerebellum TMS". Results: TMS of the cerebellum is used in two types of protocols. The first type involves the separate stimulation of the cerebellum while tracking its clinical or electrophysiological influence on motor and non-motor functions. The second involves stimulation of the cerebellum as a conditioning stimulus before stimulating the motor cortex, to monitor the electrophysiological impact of cerebellar stimulation on the motor cortex. Most studies are performed on small groups of healthy volunteers; isolated studies are performed on patients with neurological disorders (spinocerebellar ataxia, migraine, dystonia, Miller Fisher syndrome). It has been shown that cerebellar TMS is able to influence motor systems, memory, and perception of time, and there is evidence of its electrophysiological effects in the frontal cortex. Conclusion: Published studies suggest that cerebellar TMS is currently only important in research. There is not yet any clear or reliable evidence of the therapeutic effects of cerebellar TMS. However, its use as a treatment method can be anticipated.

Aim: The aim of this study was to assess accuracy of echocardiography in the measurement of left ventricular ejection fraction (LVEF), enddiastolic volume (EDV) and endsystolic volume (ESV) compared with gated SPECT. Methods: A total of 70 patients with left ventricular systolic dysfunction were enrolled to study. Median of the time interval between gated SPECT and echocardiography was 1 hour. Results: Echocardiography was in good agreement with gated SPECT for quantification of LVEF by using Simpson's method in triplane (r=0.88, p<0.001), biplane (r=0.83, p<0.001) and monoplane apical four chamber projections (A4CH) (r=0.71, p<0,001). LVEF measured by SPECT (36.6±11.5%) was non-significantly higher then triplane (35.9±10%, median dif. 0.4%), biplane (35.7±10%, median dif. 0.7%), A4CH monoplane (36.6±12.2%, median dif. 0.1%). Echocardiography correlated with SPECT in quantification of EDV using triplane (r=0.8, p<0.001), biplane (r=0.81, p<0.001) and monoplane echocardiography (r=0.76, p<0.001). EDV measured by SPECT (201.1±72.5 ml) was significantly different and higher then triplane (174.4,5±60.8 ml, median dif. 22.8), biplane (170.9±58.4, median dif. 28 ml) and monoplane echocardiography (173.7±59.3, median dif. 85.7 ml). Echocardiography correlated with SPECT in quantification of ESV by triplane (r=0.87, p<0.001), biplane (r=0.86, p<0.001) and monoplane echocardiography (r=0.83, p<0.001). ESV measured by SPECT (133.1±64.3) was significantly different then triplane (115.1±52.1, median dif. 17 ml), biplane (113.2±51.5, median dif. 15.5 ml) and A4CH monoplane echocardiography (112.5±48.8, median dif. 17.2 ml). Conclusion: Echocardiography is a valid tool for LVEF assessment and systematically underestimates LV volumes compared with gated SPECT in patients with LV systolic dysfunction.

Backround. Borderline personality disorder (BPD) is typically characterized by instability and impairmed behaviour, affectivity, interpersonal relations and lifestyle. The most common condition comorbid with BPD is a depressive episode. Depression is associated with severe disturbance of the circadian rhythms. This is apparent in depressive patients with BPD. Both sleep and diurnal rhythms are disturbed and the symptoms fluctuate. Bright light may be an effective in treatment of seasonal affective disorder, circadian sleep disorder and jet lag. It also improves sleep-wake patterns and behavioural disorders in hospitalized patients with Alzheimer's disease. Several studies have suggested antidepressant effects of phototherapy in non-seasonal depressive episodes. The treatment of comorbid depressive disorder and borderline personality disorder (BPD) is usually reported to be less successful than the treatment of patients without personality disorder. Studies describing the use of bright light in depressed patients with comorbid BPD have not been published so far. Method: The aim of this open study was to assess the effectiveness of a 6-week combined therapy with the application of bright light (10,000 lux, 6:30 to 7:30 a.m. for 6 weeks) added to SSRIs in drug-resistant depressed patients with comorbid BPD who did not respond with improvement to 6-week administration of antidepressants. The study comprised 13 female patients who met the ICD-10 diagnostic criteria for research and the DSM-IV-TR diagnostic criteria for major depression. The participants were regularly evaluated using the CGI, HAMD and MADRS scales and the BDI and BDI self-report inventories. Results: According to all the assessment instruments, the application of bright white light leads to a significant improvement. However, the results must be interpreted with caution due to the open nature of the study.

Background: Ileus states are serious conditions that may lead to pathophysiological changes which in turn can result in perforation of bowel, peritonitis, sepsis or death. Our paper discusses paralytic ileus states, which can be caused by psychopharmaceutics with anticholinergic side effects. Methods and Results: Retrospective analysis of cases of paralytic ileus in mentally ill patients admitted to Mental Hospital Kromeriz. Conclusion: Although some old psychopharmacs have a much higher potential for anticholinergic side effects than the new ones, there are still some of the new modern antipsychotics which also have anticholinergic side effects which could cause paralytic ileus. Both psychiatrists and surgeons should pay attention to atypical or changed signs of ileus states in mentally ill patients and should be aware of the confounding factors which could make the diagnosis of ileus difficult in mentally ill patients.