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Aim: Determination of the importance of exercise tissue Doppler echocardiography in prognostic stratification of congestive heart failure patients with systolic dysfunction. Methods: 106 patients with congestive heart failure and LVEF ≤ 45% on optimal pharmacotherapy were included in the study. Results of resting and post-exercise echocardiography, cardiopulmonary exercise test and serum BNP levels were available for all patients. Two patient groups were constituted, based on the prognostic classification. Group I contained 21 patients with poor prognosis (defined by predicted value of pVO2 < 76% together with both VE/VCO2 slope > 32.7 and BNP > 210 pg/mL) and group II with 85 patients who did not meet the criteria. Results: The patient groups significantly differed in indexed volume of left atrium, mitral regurgitation severity, rest and post-exercise systolic velocity of mitral annulus and in rest and post-exercise E/Em. Multivariate analysis identified E/Em as the only independent predictor of prognosis. E/Em at rest (post-exercise) ≥ 16.6 (≥ 18.7) defined poor prognosis with sensitivity of 71% (86%) and specificity of 71% (71%). Conclusion: Our study suggests usefulness of exercise tissue Doppler echocardiography for prognostic stratification of patients with congestive heart failure with possible superiority to resting parameters.

The Supplement 1 of Biomedical Papers, Vol. 151 (2007) contains contributions presented at the 57th Pharmacological Days, in other words, at the 57th Czech and Slovak Pharmacological Meeting. This meeting takes place in Olomouc, on September 12–14, 2007. Palacky University at Olomouc is pleased to host this event which represents a traditional gathering of pharmacologists, toxicologists and scientists interested in fi elds overlapping with these two broadly defi ned fi elds of biomedical sciences. It is also a good tradition that this meeting is a truly Czecho-Slovakian one with participants coming from both sides of the friendly borders between Czech and Slovak Republics. Olomouc is, in many aspects, an almost ideal place for meetings of scientifi c communities. It is a city with the second oldest University in the Czech Republic (after Charles University of Prague), founded in 1573 which is also known for their famous former students, e.g. Albrecht Eusebius Valdstejn (Wallenstein) or Gregor Mendel. Its location, not much distant from Prague, Bratislava, Cracow, Vienna or Budapest makes Olomouc a lively city full of students and scholars coming from all places of the world. We believe that the 57th Pharmacological Days will off er a good opportunity for mutual exchange of ideas and for meeting of friends and coworkers.

Background: Previously identified as a breast and ovarian cancer susceptibility gene, BRCA1 has gained major scientific interest as a potential prognostic and/or predictive marker for various tumors, including non-small-cell lung cancer (NSCLC), the leading cause of cancer related mortality worldwide. BRCA1 plays a central role in DNA damage response (DDR. It undergoes phosphorylation by various DDR kinases at different serine residues, of which ser1524 is known to be specifically phosphorylated by ATM in response to genotoxic stress. Methods: We performed BRCA1 immunohistochemistry on several tissue microarrays (TMAs) of 113 early (I, II stage) and advanced (III, IV stage) NSCLCs, using MS110 antibody against the BRCA1 N-terminal and S1524 antibody against the phosphorylated form of BRCA1 protein at ser1524 (Abcam). Patients with III and IV stage disease were treated by adjuvant cisplatin-based chemotherapy. Staining results were correlated with overall survival (OS), disease free survival (DFS) and with the occurrence of brain metastases. Results: BRCA1 S1524 nuclear positivity was significantly correlated with longer OS and DFS in stage I and II patients (P<0.05), while OS and DFS were shorter in S1524 positive stage III and IV patients (P<0.05). No significant correlation was found with brain metastases. Conclusion: The results show that BRCA1 phosphorylaton, at least in ser1524, differentiates the fate of early and advanced NSCLC as well as response to chemotherapy, but the underlying mechanisms are not completely understood. Detection of phosphorylated forms of BRCA1 might serve as a useful prognostic and predictive marker for patients with NSCLC.

Aims: Orthostatic stimuli are known to elicit changes in vasoactive peptide levels. The hypothesis of no difference in adrenomedullin and/or galanin levels in patients with recurrent vasovagal syncope and healthy controls was tested in a passive 35-min head-up tilt test (HUTT). Methods: Twenty eight persons (14 patients and 14 healthy controls) were tested in a 35-min/60° head-up tilt test with telemetry monitoring. Three blood samples were evaluated for each person during the HUTT. Plasma levels of adrenomedullin and galanin were analysed by the Kruskal-Wallis test for all sampling periods. Vagal influence was indirectly assessed by the break index. Results: There were no significant differences between groups in median values for either adrenomedullin or galanin plasma levels (all 6 p-values were greater than 0.4). For adrenomedullin, no significant difference between groups was found. For galanin, the rate of change between the 1st and 2nd measurement was significantly greater for patients (P=0.04), regardless of HUTT result but between the 2^nd and 3^rd measurement it was insignificant (P=0.36). In the group of positive cases, the break index increased significantly (P=0.02). Conclusion: We confirmed that there is a different galanin secretion pattern during orthostatic provocation in patients with recurrent vasovagal syncope than healthy individuals. For adrenomedullin, no significant difference was found. A significant increment of the break index confirmed increased vagal influence in the subgroup of positive cases.

Aims: To determine the impact of HLA compatibility measured by the Compatibility Index, on survival, rate of rejections, malignancies and infections in patients after heart transplantation (HTx). Methods: We carried out a retrospective analysis of 182 consecutive patients who underwent heart transplantation in our center from January 2001 to April 2010. According to degree of HLA-A, B and DR matching (Compatibility Index, CI) the patients were divided in two groups, Group A (n=83) with an IC 0-17 and group B (n=99) with an IC 18-26. There was no significant difference in demographic parameters between recipients and donors. Results: We found no difference in rates of rejections or infections between Group A and Group B (AR: 22 (26.5%) vs. 34 (34.3%), P=0.2539; infections: 21 (25.3%) vs. 27 (27%) P=0.7637). The distribution of infections in terms of type (bacterial, viral, fungal, including Aspergillus) was similar in both groups. The incidence of malignant tumours was infrequent (3 (3.6%) vs. 4 (4.0%), P=0.8817). We found trend toward lower level of tacrolimus in Group A. Long term survival was similar in both groups. Conclusions: Based on the results of our single-center trial, we found no impact of higher degree of HLA-A,-B, and -DR matching on survival, rejection episodes or infection. Further large studies are necessary to confirm our hypothesis that subjects with better HLA compatibility could require lower dose immunosuppression.

Background: Plasma N-terminal fragment of pro brain natriuretic peptide (NT-proBNP) concentration is elevated in cardiovascular diseases such as congestive heart failure, where increased levels of NT-proBNP indicate cardiac dysfunction, hypervolemia, and higher risk of hospitalization and death. These associations apply also to patients with severe impairment of kidney function. Little is known about diferences in plasma level of NT-proBNP in patients receiving hemodialysis (HD) versus those receiving continuous ambulatory peritoneal dialysis (CAPD). Aim: To evaluate differences in plasma NT-proBNP concentration between HD and CAPD patients. Methods: Plasma NT-proBNP concentration was prospectively measured in consecutive patients receiving either HD or CAPD at our hospital center. All other standard clinical parameters were recorded. The correlation between plasma NT-proBNP concentration and the type of dialysis was then examined. Results: We studied 99 consecutive patients on HD (age 62 ± 15 years, 66% male) and 18 consecutive patients on CAPD (age 56 ± 18 years, 67% male). Both groups had similar baseline characteristics including duration of dialysis, left ventricular function and mass, and cardiothoracic ratio. Significantly more patients on HD had abnormal NT-proBNP levels compared to patients on CAPD (97% vs 44%; P<0.0001), and this difference remained highly significant when using various NT-proBNP cut off values. A subgroup analysis revealed that the lower NT-proBNP levels of CAPD patients are most pronounced in patients with preserved left ventricular ejection function. As expected, NT-proBNP levels correlated negatively with left ventricular function and positively with cardiothoracic ratio, and this applied to both HD and CAPD groups. Conclusion: The lower concentration of NT-proBNP in patients on CAPD compared to those on HD suggests that CAPD produces lesser hemodynamic stress, especially in patients with preserved left ventricular systolic function. Even though increased NT-proBNP levels have been shown to predict increased morbidity and mortality, further studies are necessary to assess the long term benefit of CAPD compared to HD.

Aims: Evaluation of serum levels of 17 cytokines and 5 adhesion molecules in patients treated for acute myeloid leukemia (AML) using biochip array technology. This approach allows multi-analytical determination from a single sample. Methods: A total of 15 AML patients were studied. Blood samples were taken at the diagnosis (active leukemia) and at circa 6 months after completion of last chemotherapy (durable complete remission in all patients). Results: Comparing cytokine and adhesion molecule levels in active leukemia and in durable complete remission, we found significant increase (P<0.01) in serum interleukin-7 (IL-7), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and significant decrease (P<0.01) in serum E-selectin. Discussion: Our results indicate that serum levels of specific cytokines and adhesion molecules (IL-7, EGF, VEGF, E-selectin) are significantly altered in patients treated for AML, reflecting activity of the disease. Further investigation is needed to establish if the changes observed in the levels of these molecules could be used as a prognostic indicator of AML.

Introduction: ADAM33 is the candidate gene most commonly associated with asthma and airway hyperreactivity (AHR). Aim: The aim of this study was to determine whether level of AHR is associated with certain alleles or haplotypes of the ADAM33 gene in asthmatic children. Methods: One hundred and nine asthmatic children and 46 controls from the general population were examined with spirometry before and after histamine and methacholine inhalation. All subjects were genotyped for single-nucleotide polymorphisms (SNPs) of the ADAM33 gene. Haplotypes were determined according to genotypes of the patient's parents. Results: We found the three most frequent ADAM33 haplotypes (a1-3) were associated with the highest level of AHR to methacholine and histamine in 66% of asthmatic children. The paternally transmitted GGGCTTTCGCA haplotype was seen in 73.3% asthmatic children with serious AHR to methacholine challenge (paternal and maternal origin of haplotype 73.3% to 37.5, P=0.046) Significant differences in the relative frequency of paternal haplotypes with high levels of AHR to histamine were found (P=0.013). Conclusion: ADAM33 haplotypes (a1, a2, a3) are associated with severity of AHR and are significantly more often transmitted in the paternal line.

Aims: The non-invasive ¹³C-methacetin (¹³C-MBT) breath test has been proposed as a measure of metabolic liver function that improves the diagnostic efficacy of serologic and biochemical tests in assessing hepatic functional capacity and liver disease severity, The goal of this study was to establish the clinical utility of this test in quantifying hepatic metabolic function in patients with liver cirrhosis of varying severity and to compare ¹³C-MBT measurements with the AST/ALT ratio, APRI score, and other routine liver tests. Methods: Routine liver function tests including serum bilirubin, aspartate aminotransferase activity (AST), alanine aminotransferase (ALT), AST/ALT ratio, the APRI score, the percentage of dose rate (PDR) and cumulative percentage of dose rate (CPDR) of the ¹³C-MBT were evaluated in 52 cirrhotic patients of alcohol etiology (Child-Pugh A/B/C 10/28/14) and 37 healthy controls. Results: The ¹³C-MBT differed significantly between healthy controls and cirrhotic patients at all time intervals measured. It also proved the ability to differentiate patients with liver cirrhosis based on severity of hepatic impairment corresponding to the Child-Pugh classification A vs. B vs. C. The ROC curve analysis suggested that the best prediction is provided by time intervals between the 10^th - 20^th or 10^th - 40^th minute of PDR. Conclusions: The ¹³C-MBT offers a reliable means for quantification of hepatic metabolic function over the complete range of functional liver impairment. It is non-invasive, easy to perform and completely safe.

The history of science, the arts, and so on, is often as equally instructive as is the science itself. It forces us to compare our contemporary knowledge with the preceding one and, since in all comparisons one must think more than in a mere one-sided observation, the history of science thus forces us to think more than the science alone reveals.

BACKGROUND: Every year about one million women worldwide are diagnosed with breast cancer which is the most common malignancy in female. Of these, triple negative breast carcinoma represents 10-17 %. Triple negative breast carcinomas, characterized by estrogen, progesterone and HER2 receptor negativity are very aggressive tumours with poor prognosis. Individualized treatment (tailored therapy) based on molecular biology markers of tumor and patient is the trend in clinical practice these days. However, molecular targets and predictors for the treatment of triple negative breast carcinoma do not currently exist. METHODS AND RESULTS: This minireview focuses on biomarkers (HER1/EGFR, TOP2A and C-MYC genes) that may predict the response of triple negative breast carcinoma patients to chemotherapy and/or targeted biological treatment with a summary of current knowledge about them. CONCLUSION: HER1 belonging to the HER family of receptors plays an important role in cell proliferation, migration and protection against apoptosis. HER1 protein could be targeted by monoclonal antibodies and/or tyrosine kinase inhibitors (TKIs). Given signal pathway complexity and HER family member cooperation, it may be better to simultaneously target a number of these receptors (e.g. HER1/HER2 by lapatinib). Thus, HER1 assessment could reveal a particular breast cancer patient group with probably good response to HER1 targeted therapy. TOP2A gene, encoding topoisomerase II alpha (target for anthracyclines) is predictive of response to anthracycline therapy. TOP2A aberrations (amplification, deletion) are found in up to approximately 30-90 % of HER2 amplified breast cancer and amplifications are more common than deletions. Recent publications describe TOP2A amplification also in 2.7-8.8 % HER2 nonamplified breast cancers. Patients with a pathologic complete response to anthracycline based neoadjuvant chemotherapy had a good overall prognosis regardless of molecular subtype of breast cancer. These results suggest that particularly tumors with a complete pathological response to anthracyclines could have TOP2A amplification. C-MYC encodes nuclear DNA binding proteins that regulate proliferation and apoptosis; amplification is associated with poor prognosis and hormonally negative breast carcinoma.

Objective: The aim of this study was to observe the relationship of the sphenoid sinus and posterior ethmoid cells with the optic nerve. Material and Methods: 34 CT scans (68 sides) of paranasal sinuses of patients older than 18 years were retrospectively reviewed. Images were assessed in two planes - axial and coronal. We observed the position and relationship of the optic nerve to the posterior ethmoid and sphenoid sinuses, bony dehiscence and protrusion of the optic nerve into sinuses, and pneumatization of the anterior clinoid process. Results: The most frequent position of optic nerve (ON) was a location close to the posterior ethmoid and sphenoid sinuses without contacting or indentation of the wall - 55.9 % (38 nerves). The bulging of ON to sphenoid sinus was found in 14.7 % (10 nerves) and the course of the nerve through sinus in 16 nerves (23.5 %). The position of ON intimately to both sinuses was observed in 5.9 % (4 nerves). Protrusion of ON, dehiscence of the bony wall and pneumatization of anterior clinoid process (ACP) was seen in 12 (35.3 %), 4 (11.8 %) and 9 (26.5 %) patients, respectively. Both the protrusion of ON and ACP pneumatization were present in 8 (23.5 %) patients on the right side and in 5 (14.7 %) patients on the left side. Conclusion: Variations of posterior ethmoid and sphenoid sinuses are numerous and may entail potential risk of injury of the ON during sinus surgery. Knowledge of individual differences and configurations in the operation area may help the surgeon to prevent complications. Computed tomography is the preferred radiographic modality for evaluation of bony variations and the pathology of this region.

Background: Nanomaterials are at the leading edge of the rapidly developing field of nanotechnology. Magnetic nanoparticles for cancer therapy and diagnosis have been developed on the basis of their unique physico-chemical properties not present in other materials. Their versatility is widely exploited in such diverse techniques as cell and macromolecule separation and purification, immunoassays, targeted drug delivery, controlled material release, electromagnetic hyperthermia, gene therapy, or magnetic resonance imaging. In this review we concentrate on the physical principles of magnetic drug targeting and biomedical applications of this technique. Methods and results: We examined several databases, PubMed, ISI Web of Knowledge, and Scopus, for the period 1985-2009, with specific attention to studies that used targeting of magnetic nanoparticles especially in the therapy and diagnostics of tumors. We have also presented several of our own results on theoretical simulations of magnetic particle motion in external magnetic field. Conclusions: We found growing number of published papers in this field of nanomedicine, showing the almost unlimited potential of magnetic nanoparticles in the field of experimental and clinical oncology.

Background: Cryptococcus neoformans is an obligate aerobic pathogenic yeast causing lung infection typically followed by spread to the central nervous system. During pathogenesis, it relies on well-established virulence factors. This review focuses on the emerging role of cryptococcal adaptation to hypoxia in pathogenesis. Methods and Results: We examined the MedLine database for information on the cryptococcal hypoxia response. While several recent papers describe components of two presumable hypoxia-sensing pathways including description of their target genes, a link of this system to the hypoxic tuning of proliferation is still missing. In addition, an interpretation of this knowledge in respect to the general picture of microbial pathogenesis is lacking. Conclusions: There seems to be a striking parallel between biofilm formation in bacteria, which results in chronic dormant infection with the potential for acute outbreaks, and the dormant state of primary infection followed by secondary outbreaks in C. neoformans. We propose a hypothesis that cryptococcal response to hypoxia might be the driving force for developing a state of dormant infection which is characterized by slowed proliferation and extensive changes in transcriptome and phenotype. This state enables C. neoformans to survive in host and possibly develop life-threatening acute outbreaks later. Hence, conventional well-aerated planktonic culture is not a good in vitro model for studying the pathogenesis of infection and we advocate the development of a more adequate model. Our further conclusion is that the ability of the immune system and antifungal agents to cope with hypoxia-adapted cells is crucial for the successful eradication of cryptococcal infection.

Backround. Suicide is the eighth leading cause of death in adults and the second leading cause of death in the 15- to 24-year-old age group. Suicidal impulses and suicidal behavior result from emotionally unbearable feeling of mental suffering and cognitive narrowing that prevent resolution to experienced stress, that is, in a situation when personal coping mechanisms have failed. Suicide attempts are a frequent cause of hospital admissions, in particular to anesthesiology and resuscitation departments. Risk factors: Women attempt suicide three times more often than men. Four times more men than women complete suicide. More than 90% of people who complete suicide are diagnosed with severe mental illness and 50% suffer from depression at the time of suicide. Assessment. Physicians should be aware of possible suicidal behavior in any patient with mental illness, especially if accompanied by depressive symptoms. The physician should approach the topic of suicide carefully and discreetly, only after a therapeutic relationship with the patient has been established. Management. Patient protection, usually in the setting of a closed psychiatric ward, is necessary if he or she has a clear plan and means to commit suicide. After the patient's safety is secured, treatment may be initiated. If the patient is treated on an outpatient basis, his/her condition must be carefully monitored.

Aims: Polymorphisms in the genes that code for metabolic enzymes involved in either the activation (Phase I) or detoxication (Phase II) of chemical carcinogens in tobacco, may alter expression or function of carcinogenic compounds and hence alter risk of oral cancer. The present study investigates whether polymorphisms at CYP1A1 and GSTM1 gene loci act as risk factors for oral precancerous lesions and cancer. Methods: For the present study, histopathologically confirmed cases of 90 oral precancerous lesions, 150 oral squamous cell carcinoma (SCC) and 150 control subjects were selected. Polymerase chain reaction and restriction fragment length polymorphism were performed using DNA from blood samples to determine the polymorphic genotypes at CYP1A1 and GSTM1 loci. Results: CYP1A1 C (m2/m2) genotype conferred a 12.0 fold-increased risk (OR=12.0; 95% CI, 2.40-60.05) to oral SCC. GSTM1 null showed no significant association but the frequency was higher in oral SCC cases. Patients with genotype C and/or GSTM1 deficiency developed carcinoma after less tobacco consumption than those of other genotypes though the difference was not statistically significant. The frequency of the combined genotypes C and GSTM1 null was found to be 14% among oral SCC patients. On comparing the susceptibility of intraoral sites it was found that in the majority of cases (64%) in the study groups they were the buccal mucosa. Conclusion: Hence it was concluded that metabolic enzymes reported in the present study: CYP1A1 significantly alter oral cancer risk. GSTM1 null and CYP1A1 C (m2m2) show a predisposition to premalignant lesions and cancer of the buccal mucosa than other sites.

Background: The prevailing recommendation for the elderly is to live in their own homes as long as conditions allow. With this emphasis on the natural living environment, it is imperative to closely monitor both the general health and nutritional needs of the elderly in community settings. Aim: The aim of the study was to compare three nutritional status screening and evaluation tools of the elderly in their homes. Methods: Testing of measuring instruments, MNA, SGA, and MUST took place in the homes of 120 seniors in selected areas of the Czech and Slovak Republics. The study included 120 seniors. For testing of the relationships and dependencies, Pearson's correlation coefficient, t and Fisher tests were used. The level of statistical significance was α = 0.05. Results: All tests were to a large degree correlated (p_MNA = 0.0049; p_MUST = -0.537; p_SGA = -0.578) with the body mass index of the seniors. Simultaneously, it was confirmed that the tools for assessing nutritional status in the study showed significant differences regarding the classification of patients at risk of malnutrition and/or malnourished patients. Conclusions: Based on the findings, we conclude that MNA appeared to be a more appropriate tool for nutritional assessment of the elderly living in their homes. SGA and MUST provided rather subjective evaluation of the nutritional status and did not furnish an in-depth categorization of malnutrition.

Aims: The impact of ApoE polymorphism on angiographic parameters was assessed in patients referred for coronary angiography. Methods: Elective coronary angiography was performed in 671 subjects (525 men, 146 women, mean age 60±10 years) with symptoms of ischemic heart disease. The patients were divided into: no CAD group (smooth coronary vessels, n=83), one-vessel (n=155), two-vessel (n=170) and three-vessel disease (n=196). Patients with stenoses 0-50% were excluded. Within patients with CAD, we evaluated overall extent of CAD measured by the number of stenotic segments according to AHA (1 segment vs. 2-3 vs. ≥4), and the severity of the most serious stenosis (in percent). ApoE genotype was determined using real-time PCR. Results: The frequency of ε2/ε3 genotype (n=56) was lower in the three-vessel disease group compared to one-vessel disease (OR=0.25, P=0.0019), two-vessel disease (OR=0.31, P=0.0114) or no CAD group (OR=0.24, P=0.0057). Frequency of ε2/ε3 decreased with the number of affected segments (1 vs. ≥4: OR=0.35, P=0.0143). The ε3/ε4+ε4/ε4 genotypes (n=123) were more frequent in CAD patients altogether compared with no CAD group (OR=2.30, P=0.019), while no impact of the ε4 allele on angiographic parameters within the CAD patients was detected. In ε2/ε3 carriers with CAD, lower LDL-cholesterol, total cholesterol and lower use of lipid-lowering drugs were observed. Conclusions: The results show predominantly focal form of CAD in patients with ε2/ε3 genotype. Lower LDL-cholesterol and total cholesterol may play the key role, although other contributing factors are discussed.

Background: We evaluated the effect of hypertension on hemodynamic responses and serum nitrite concentrations in normotensive (NT) and deoxycorticosteron acetate (DOCA)-Salt hypertensive (HT) rats. Methods: Uncontrolled hemorrhagic shock was induced in NT and HT rats (n=7 each) by preliminary bleed of 25 ml/kg followed by a 75% tail amputation. The mean arterial pressure (MAP), heart rate and serum nitrite were measured pre-hemorrhage and during hemorrhage. Results: Changes in time-averaged MAP after hemorrhage were significantly greater in HT group than NT. After resuscitation, the HT rats failed to restore MAP to baseline level. Serum nitrite level in both groups was significantly increased during shock period. Survival rate of HT animals was lower than NT group, although it was not statistically significant. Conclusions: Marked reduction of MAP and less improvement after resuscitation suggested the less adaptation of cardiovascular system in HT animals which may interfere with management of these subjects during uncontrolled hemorrhagic shock.

Background. BRCA1 (Breast cancer 1) was previously identified as a breast and ovarian cancer susceptibility gene, but recently gained a major scientific interest as a prognostic and/or predictive marker for various tumors, including non-small cell lung cancer (NSCLC), which is the leading cause of cancer related mortality in the world. We aimed to review the role of BRCA1 in NSCLC based on currently available literature. Methods: We performed the literature search in Pubmed database, using key words: BRCA1, non small cell lung cancer, chemotherapy, drug resistance. Articles published in English were selected for review. Results: Research papers are mainly focused on BRCA1 mRNA expression studies in response to DNA damaging chemotherapy. Several articles about genetic and epigenetic changes of BRCA1 in NSCLC were also available. Conclusions: BRCA1 is a multifunctional tumor supressor protein, which plays a key role in essential cellular processes and modulates the cellular response to cytotoxic chemotherapy. With the difference from breast and ovarian cancer, BRCA1 has no role in NSCLC cancerogenesis and mainly discussed as a promising genomic marker for customized chemotherapy in NSCLC patients.

Aim: To compare the quality of magnetic resonance angiographies (MRAs) performed with different contrast agents and to evaluate the effect of body mass index (BMI) and ejection fraction (EF) on the quality of these MRAs. Materials and Methods: 120 patients between the age of 43 and 86 years were subjected to MRAs with different contrast agents (Gadobutrolum, Dimeglumini gadobenas, Gadofosveset trisodium). Each patient's BMI was calculated, and EF was established using MR examination of the heart. Objective evaluations of the quality of the MRAs were done using abdominal fat-to-aorta enhancement ratio (FAR) comparisons. This ratio was then correlated with the patient's BMI and EF. Subjective evaluations of the quality of the MRAs were done by 5 blinded evaluators. Correlation analysis and analysis of variance were used for statistical assessement. Results: There was no statistically significant difference in FAR for any of the contrast agent groups. There was a mesoscale correlation between a patient's BMI and FAR. However, no correlation was found between the EF and FAR for any of the contrast agent groups. The results of the subjective evaluation showed that there was no statistical difference in the quality of MRAs regardless of the contrast agent used. Conclusion: Subjectively there was no statistically significant difference in the quality of the MRAs. Irrespective of the type of contrast used or the patient's EF, the lower the BMI of a patient the higher the signal enhancement and hence the better the quality of the MRA produced in that patient.

Objective: Supervision is a basic part of training and ongoing education in cognitive behavioural therapy. Self-reflection is an important part of supervision. The conscious understanding of one's own emotions, feelings, thoughts, and attitudes at the time of their occurrence, and the ability to continuously follow and recognize them are among the most important abilities of both therapists and supervisors. The objective of this article is to review aspects related to supervision in cognitive behavioural therapy and self-reflection in the literature. Methods: This is a narrative review. A literature review was performed using the PubMed, SciVerse Scopus, and Web of Science databases; additional references were found through bibliography reviews of relevant articles published prior to July 2011. The databases were searched for articles containing the following keywords: cognitive behavioural therapy, self-reflection, therapeutic relationship, training, supervision, transference, and countertransference. The review also includes information from monographs referred to by other reviews. Results: We discuss conceptual aspects related to supervision and the role of self-reflection. Self-reflection in therapy is a continuous process which is essential for the establishment of a therapeutic relationship, the professional growth of the therapist, and the ongoing development of therapeutic skills. Recognizing one's own emotions is a basic skill from which other skills necessary for both therapy and emotional self-control stem. Therapists who are skilled in understanding their inner emotions during their encounters with clients are better at making decisions, distinguishing their needs from their clients' needs, understanding transference and countertransference, and considering an optimal response at any time during a session. They know how to handle their feelings so that these correspond with the situation and their response is in the client's best interest. The ability to self-reflect increases the ability to perceive other people's inner emotions, kindles altruism, and increases attunement to subtle signals indicating what others need or want. Self-reflection may be practised by the therapists themselves using traditional cognitive behavioural therapy techniques, or it may be learned in the course of supervision. If therapists are unable to recognize their own thoughts and feelings, or the effects of their attitudes in a therapeutic situation, then they are helpless against these thoughts and feelings, which may control the therapist's behaviour to the disadvantage of the client and therapist alike. Conclusion: Training and supervision focused on self-reflection are beneficial to both supervisees and their clients. The more experienced the supervisor is, the more self-reflection used in therapy and supervision.

Aim: To determine intravitreal and plasma concentrations and retinal toxicity after transcorneal intravitreal injection of 1 μg and 2 μg of topotecan (Hycamtin). Method: Twelve healthy albino rabbits were included in this in vivo experiment. Six anesthetized albino rabbits received a single transcorneal intravitreal injection of 1 μg (group A) or 2 μg (group B) of topotecan. Vitreous and blood samples were collected until 168 h. Left eyes were treated with the same volume of saline. Plasma and vitreous levels of topotecan were determined by high-performance liquid chromatography. Area under the plasma concentration time curve (AUC) was calculated using trapezoidal rule. Clinical evidence of toxicity was classified into four grades according to anatomical structures. Electroretinograms (ERGs) were recorded. Results: Time to maximum concentration was observed up to 2 h after drug injection in group A whereas up to 1 h in group B. Low levels of topotecan were detected in plasma in both groups and in the vitreous humor of the contralateral eye in group B. Topotecan levels (mean vitreous AUC in group A 2.55 μg/mL.h and in group B 5.338 μg/mL.h) were detectable up to 6 h in both groups. We observed following structural changes in rabbit eyes: corneal vascularization, cataract, hemophthalmus, choroidal edema and focal retinal atrophy. Abnormal ERGs were obtained. Conclusion: Our findings proved that transcorneal intravitreal administration of 1 μg and 2 μg of topotecan results in potentially cytotoxic intraocular concentrations. More studies are needed to establish the safety of topotecan for retinoblastoma in children.

Background: AECOPD is a life threatening condition for patients with chronic obstructive pulmonary disease (COPD) and lack of specific biomarker hinders effective management. Sputum, blood, breath and urinary biomarkers have all been investigated. We measured maximum respiratory pressure post exacerbation once the patient was compliant with the test and after 6 weeks, to assess any correlations. Methods and Results: The maximum pressures were measured using a closed circuit spirometer with a clean rubber mouthpiece properly placed with the patients lips sealed around it. Patients were properly instructed to exhale slowly and completely, then inspire with maximum possible effort and advised to keep it for nearly 1.5 s for maximum inspiratory pressure (MIP). For maximum expiratory pressures (MEP) patients were instructed to inspire slowly and completely, then expire forcefully with maximum effort. With the recorded values TTI (time tension index) was calculated. This was repeated again after 6 weeks. Using Pearsons correlation coefficient we found that MIP had a negative correlation with TTI and a positive correlation with FEV1. FEV1 had a positive correlation with FVC. MEP showed no significant correlation with TTI, but a positive correlation with FEV1. Conclusion: Acute exacerbations of COPD has a profound effect on the respiratory musculature especially the expiratory muscles but the maximum pressures are not specific enough to be prognostic markers. It might be worthwhile studying transformations of the respiratory musculature at the molecular level. More studies must be conducted to find a specific marker to aid in the management of the condition.

Aims: To evaluate the incidence of severe hypoglycaemia (SH) requiring the assistance of Emergency Medical Services (EMS) in the general population of the Hradec Králové region, in a 1 year period; to describe the distribution of these events throughout the day, and to analyse the symptoms and causes. Methods: The outcome data were obtained from special forms which were filled in by EMS medical staff. Incidence of SH was calculated and the distribution of events throughout the day was analysed using contingency tables. The relationship between blood glucose levels and the presence or absence of causes and symptoms of hypoglycaemia was evaluated using a general linear model and the regression tree technique. Results: In all, a total of 338 events of SH were recorded in 262 patients. 150 episodes appeared in type 2 diabetic patients, 83 episodes in type 1 diabetic patients. 258 events were documented in insulin-treated patients. The incidence of SH was 2.4 and 0.4 episodes/100 patients/year for type 1 and type 2 diabetic patients, respectively. A significantly greater number of hypoglycaemic episodes was documented between 2 pm and 6 pm (P<0.001). Insulin therapy and alcohol consumption were the most dangerous causes of SH. Conclusions: Hypoglycaemia requiring the assistance of EMS represents an essential problem, especially in type 1 diabetic patients. The percentage of SH is comparable to other frequent diagnoses requiring the assistance of EMS in the region. This study reflects the behaviour of diabetic patients and highlights information which is important in the prevention of SH.

Objective: The aim of the survey was to identify the needs of mothers to infants hospitalized in intensive care units (ICUs) and second, to assess the level of parental support provided by the health personnel. Methods: The sample consisted of 147 mothers to infants hospitalized in ICUs. The research was conducted over six months in ICUs for newborns at two hospitals in Ostrava. The study used two standardized questionnaires: The parental stressor questionnaire scale: Neonatal Intensive Care Unit which measures the degree of stress in parents of hospitalized infants and the questionnaire The Nurse Parent Support Tool which evaluates the level of parental support provided by nursing staff. Results: The highest level of stress was identified in the parental role. Specifically, the inability to help the child remain separate from the mother, a feeling of helplessness and inability to protect the child from painful procedures and the inability to feed her baby. Mothers evaluated the support of nursing staff in most of these areas as high. Top were rated the ability of the caring staff to respond well to the questions of parents and the mother's willingness to engage in childcare. Conclusion: Intensive care units for the newborn obviously need to be family-centered care and at the same time they must be aware of all the factors that can be sources of stress for the parents.Only in this way can stress be eliminated with positive impact on the relationship between mother and child.

Background: Humoral systems play an important role in the patophysiology and development of chronic heart failure (CHF). Methods: We conducted a search of neurohumoral activation in heart failure and its risk in the development of CHF. Results and conclusion: Neurohumoral factors may be divided into vasoconstrictive, vasodilative and cytokines. The main vasoconstrictive systems are the renin-angiotensin-aldosterone system (RAAS) and the sympathoadrenal system (SAS). Cytokines include tumour necrosis factor (TNF) alpha and interleukins. The systems of actions are interconnected and they mutually influence their secretion and activities. The possibilities of their detection and assessment for clinical purposes depend on their changes and kinetics in the organism and on the activity of individual metabolites. Apart from their vasoactive effects, the majority of humoral actions also interfere in the process of remodelling, function of the endothelium, blood elements, cardiomyocytes, cells of the smooth muscles, and in immunity as well as inflammatory processes. The rapid development of knowledge on the humoral actions in recent years has made possible their utilisation in diagnostics, treatment and prognosis.

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.