[Survival Analysis Three-year Follow-up of Pacients with Head and Neck Cancer]. / Analýza prezití tríletého sledování nemocných s rakovinou hlavy a krku.

BACKGROUND: Patients with head and neck cancer are predominantnly at the risk for malnutrition. Monitoring of nutritional status and pre-treatment variables can favorably observe many prognostic indicators for overall survival in head and neck cancer before and during oncological treatment up to three years in head and neck cancer pacients. MATERIALS AND METHODS: In 726 patients diagnosed head and neck cancer patients with curative intent, were collected data according to the monitoring scheme of observation. As a clinical important of uninteded weight loss was defined weight loss 10% in input (T0). Differences in groups were analysed by Coxs regression with adjustments for important demografic and tumor-related data. RESULTS: The acceptance of the percutaneous endoscopic gastrostomy was a key factor for less complications and to improve tolerance of anticancer treatment. Men-smokers have the highest risk of cardiovascular mortality. Men-stop-smokers have the most significant life extension of 11 to 22 months; p < 0.007. Men-non-smokers have a life extension of 15 to 23 months (p < 0.005) and having its lowest cardiovascular mortality (11%). Women tolerate cancer better, have minor subjective complaints and a lower number of complications but significantly higher consumption of antidepressants (p < 0.003). While men have higher analgesic consumption (p < 0.001). Weight loss > 10% significantly correlates with the clinical manifestations of malnutrition and is associated with an increase in complications and mortality dependent cancer (p < 0.008). CONCLUSION: Consistent assessment of nutritional status with early intervention is considered as an essential part of comprehensive anticancer treatment. An independent risk factor for cancer-dependent mortality is considered weight loss of > 5% with a BMI < 21 at time T0 or weight loss > 10% weight T0 in BMI 21- 29 and continuing weight loss to T12 and also BMI 30. The highest-risk profile has a male sex-smoker, age > 63, hypopharyngeal carcinoma, stage III- IV, weight loss of > 10% and non-acceptance of percutaneous endoscopic gastrostomy. Another long-term observation of monitored nutritional status with intervention, clinical status and quality of life are needed.

[Long Term Monitoring of Nutritional, Clinical Status and Quality of Life in Head and Neck Cancer Patients]. / Dlouhodobé sledování nutricního, klinického stavu a kvality zivota u nemocných s rakovinou hlavy a krku.

BACKGROUND: Malnutrition in head and neck cancer (HNC) patients decreases survival, quality of life (QOL) and oncological outcomes. The aim of the prospective three-year study was to compare QOL, clinical symptoms and variables (complications, survival and mortality rates in HNC patients). PATIENTS AND METHODS: A total of 726 patients aged 55 to 72 years with treatable HNC were included from January 2004 to December 2009; these patients were randomized to either group with PEG and enteral nutrition and nonPEG group with nutritional counselling according to nutritional care. We used EORTC questionnaires QOL C-30 and Head and neck module (HN-35) for measuring of QOL. The following variables due to expectable influence on QOL (demographic data, oncological data, nutritional screening, Clinical symptom score, Karnofsky performance status score, Charlson comorbidity index) were included. Monitoring was done five times in three years. RESULTS: In the first six months, we found decrease of weight and body mass index (BMI). After this critical time point and finish of oncological treatment, a marked difference in the development of patients treated with PEG. Negative factors influencing patients survival, QOL, clinical status were males aged > 63 years, hypopharyngeal cancer (stage III- IV), smoking, weight loss > 10%, BMI < 21 and disallowance of PEG. CONCLUSIONS: QOL is an essential factor for cancer patients. Our study showed that nutritional intervention with early enteral nutrition may improve QOL and survival in HNC patients. The PEG group better tolerated oncological treatment, had lower incidence of complications, shorter time to re-entry of permanent increase in weight, lower rate of rehospitalization and its shorter length. We found QOL questionnaires to be very important for better understanding and communication and a key instrument for improving solution of patients difficulties during their therapy in multidisciplinary approach.

Impairment of nasal mucociliary clearance in former smokers with stable chronic obstructive pulmonary disease relates to the presence of a chronic bronchitis phenotype.

BACKGROUND: Associations between nasal and bronchial impairment have been repeatedly described in chronic obstructive pulmonary disease (COPD), whereas nasal mucociliary clearance (MCC) in COPD patients is not yet fully understood. We studied nasal MCC parameters in COPD patients and compared them with healthy adults (HA) and with cystic fibrosis (CF) patients with compromised MCC. METHODOLOGY: An observational study of 98 COPD ex-smokers and subjects from control groups evaluated for nasal MCC time (NMCCt) and by digital video microscopy of nasal mucosa recording ciliary beat frequency (CBF) and ciliary beat pattern. RESULTS: The NMCCt was decreased in HA compared to those with COPD and decreased in those with COPD compared to those with CF. CBF in COPD was lower compared to HA. The index of ciliary dyskinesia in COPD patients differed from HA. We detected higher NMCCt and lower nasal CBF in patients with chronic bronchitis phenotype (CB) compared to non-CB patients. CONCLUSIONS: We confirmed the presence of impaired nasal MCC in COPD ex-smokers. These impairments were apparent predominantly in the CB phenotype.

Rapid onset of ICAM-1 expression is a marker of effective macrophages activation during infection of Francisella tularensis LVS in vitro.

Francisella tularensis is capable to modulate immunobiological activities of the host cells. We focused on the expression of ICAM-1 (CD54) on J774.2 mouse macrophage cell line infected by F. tularensis live vaccine strain (LVS) in vitro as a putative marker of subsequent elimination of infection. J774.2 cell line cells were infected by F. tularensis LVS strain (multiplicity of infection, 1:100). Cell cultures were stimulated either 3 h before infection or 3 h after infection by either lipopolysaccharide (LPS) or interferon γ (IFN-γ). The expression of ICAM-1 was determined by flow cytometry 6 h after infection. The intensity of ICAM-1 expression after 6 h of J774.2 macrophage cells infection by F. tularensis is very sensitive indicator of the effective macrophages stimulation resulting in the elimination of F. tularensis infection. The mean fluorescence intensity MFI = 49.8 is set-up by our experiments as a reliable threshold of the effective elimination of F. tularensis experimental infection with 83.3% sensitivity and 96.7% specificity, respectively. Simultaneous stimulation of J774.2 macrophage cells by LPS and IFN-γ was essential to elicit the elimination of F. tularensis infection. The ICAM-1 expression determined by flow cytometry can be considered to be highly sensitive and specific approach to predict elimination of F. tularensis infection by J774.2 macrophages.

Failure of noninvasive prediction of pulmonary hypertension in patients with idiopathic pulmonary fibrosis.

BACKGROUND: Pulmonary hypertension (PH) in patients with advanced idiopathic pulmonary fibrosis (IPF) is a complication connected with unfavorable prognosis. Great efforts have been made in attempting to establish a reliable non-invasive method which would enable detection of this complication. In this context a formula using pulmonary function parameters was published with outstanding results. METHODS: We tested the formula in 27 IPF patients who underwent a lung function examination, cardiac ultrasonography and catheterisation on the same day. RESULTS: Pulmonary hypertension was detected by catheterisation in 17 patients (63%). In our group, contrary to the published data, the aforementioned formula was neither useful for detecting patients with a high probability of PH nor as a means of calculating the mean pulmonary artery pressure in individual patients (p = 0.502 and p = 0.833, respectively). Ultrasound examination reached borderline correlation with the values measured by catheterisation when we compare patients with relevant results (r = 0.531, p = 0.051). However, the examination gave no usable results in 13 patients (48%). CONCLUSION: Our data suggests that no reliable, noninvasive method is currently available for detecting and confirming PH in IPF patients. We did not confirm the usefulness of the published formula. Further carefully organised studies will be necessary to verify or refute it.

J774 macrophage-like cell line cytokine and chemokine patterns are modulated by Francisella tularensis LVS strain infection.

Mutual interactions were investigated between intracellular parasitic bacterium Francisella tularensis (F.t.; highly virulent bacterium responsible for tularemia, replicating within the host macrophages) and murine macrophage-like cell line J774. Recombinant murine lymphokine INF-gamma and/or LPS derived from E. coli were determined to stimulate in vitro antimicrobial activity of macrophage-like J774 cell line against the live vaccine strain (LVS) of F.t. through their ability to produce proinflammatory cytokines and chemokines. F.t. infection up-regulated IL-12 p40 production and down-regulated TNF-alpha production by stimulated macrophages; on the other hand, F.t. infection did not affect the production of IL-8, IL-6, MCP-5, and RANTES by stimulated macrophages. This showed that F.t. infection modulates the cytokine synthesis by J774 macrophage cell line.

[Mucosal immunity with emphasis on urinary tract immunity and diabetes]. / Imunita na sliznicích se zretelem na sliznici urogenitálního traktu a diabetes.

Protective immune response in urinary tract is frequently impaired in patients with diabetes. Immunity in this mucosal compartment displays unique characteristics; e.g. absence of physiological microflora and lack of mucus. Pathogens are identified by the PRR receptors expressed on both epithelial and immune cells. Inflammatory response characterised by the acumulation ofgranulocytes is followed. Both protective and harm characteristics of inflammatory response are inseparable linked and delineated by gene polymorphisms in PRR receptors.

[Long term effectiveness of surgical cryoablation for chronic atrial fibrillation in patients undergoing surgery for severe mitral valve regurgitation]. / Dlouhodobá úcinnost chirurgické kryoablace chronické fibrilace síní provedené pri operaci pro závaznou mitrální regurgitaci.

OBJECTIVE: The objective of the study was to evaluate effectiveness of surgical cryoMAZE ablation for chronic atrial fibrillation (AF) in patients undergoing mitral valve surgical intervention. METHODOLOGY: Forty-seven patients (31 females), aged 67.3 +/- 7.3 years who underwent surgical intervention for severe mitral regurgitation were studied. Mitral valvuloplasty was performed in 21 patients, and mitral valve replacement in 26 patients. Combined procedure was employed in 35 patients; simultaneous aortocoronary bypass was performed in 16 patients, tricuspid valvuloplasty (TVP) in 5 patients, and aortic valve replacement (AVR) in 5 patients. RESULTS: The mean follow-up time was 19 +/- 10 months. After 6 or 12 months 36 or 32 patients were seen and 23 (64%) or 22 (69%) of them were in stable sinus rhythm (SR), respectively. In the subset of 24 patients with simultaneous intervention on a different valve (TVP or AVR), after 6 or 12 months, 14 (74 %) or 15 (83 %) patients had stable SR, respectively. In the follow-up period, 2 patients underwent successful catheter ablation for type I atrial flutter or for a residual left atrial atypical flutter. CONCLUSION: In the study using the method of cryoMAZE ablation for chronic AF performed during the mitral valve surgical intervention, a long-term stable SR was achieved in a high proportion of patients, particularly in patients with simultaneous intervention on two or three different valves.

[Innate immunity, receptors for exogenous and endogenous danger patterns in immunopathogenesis of atherosclerosis--part II: TLR receptors, significance of genetic polymorphism of danger signals receptors]. / Pirrozená imunita, receptory pro exogenní a endogenní nebezpecné vzory v imunopatogenezi aterosklerózy II. cast. Receptory TLR, význam polymorfizmu receptoru pro nebezpecné vzory.

The most important set of receptors for danger patterns are TLR receptors. Together ten different TLR receptors were identified so far. Majority of TLR receptors is expressed on the cell surface to identify extracellulary localized danger signals. Some TLR receptors are also expressed in the intracellular compartment to identify intracellular danger signals. Receptors for danger signals display individual differences delineated by genetic polymorphism. The individual immune reactivity is developed in the context of genetic predisposition and the exposition to variable environmental factors. The differences in an individual immune reactivity are probably responsible for individual susceptibility or resistance to the development of immunopathological reactivity, which is involved in the immunopathogenesis of atherosclerosis.

[Innate immunity, receptors for exogenous and endogenous danger patterns in immunopathogenesis of atherosclerosis--part 1: identification of danger signals by innate immunity]. / Prirozená imunita, receptory pro exogenní a endogenní nebezpecné vzory v imunopatogenezi aterosklerózy I. cást: Prirozená imunita, rozlisení signálu nebezpecí.

Cellular and humoral components of innate immunity are able to identify danger signals both of the exogenous and endogenous origin. Exogenous danger signals are evolutionary conserved mosaics of danger patterns which are frequent in pathogenic microbes. Endogenous danger signals are raised during damage of self structures, by oxidative stress and/or by chemical modification of self molecules. Danger signals are identified by several families of molecules which are expressed on the surfaces of innate immunity cells. Among them the TLR receptors family which is associated with intracellular signaling pathway NF-kappaB is one of the most important. The inflammatory response is induced via activated NF-kappaB transcription factor.

[Multidrug resistance markers monitoring in acute myeloid leukemia cells]. / Sledování vybraných znaku mnohocetné rezistence k cytostatikum u leukemických bunek pacientu s diagnózou akutní myeloidní leukémie.

BACKGROUND: P-gp, MRP, LRP, Bcl-2, and Bax proteins play an important role in the multidrug resistance of leukemic cells. P-gp, MRP, and LRP proteins decrease the intracellular drug concentration, Bcl-2 and Bax proteins influence the apoptosis process. The overexpression of some of these proteins is associated with poor prognosis of leukemia. The aim of this study was to find the relationship between some multidrug resistance markers and some clinical and laboratory parameters. We compare also P-gp expression between acute myeloid leukemia (AML) FAB subgroups M0-M6. METHODS AND RESULTS: With use of flow cytometry we measured the expression of P-gp, MRP, LRP, Bcl-2, and Bax proteins in acute myeloid leukemia patients cells. The study proved the association between blast percentage and P-gp protein expression (p=0.015) and the association between blast percentage and Bcl-2 protein expression (p=0.041). It was also shown the tendency of the LRP protein expression to associate with higher age of patients (p=0.062). Another correlation between MRP and Bax expression (p=0.006), as well as between LRP and Bax expression was found (p=0.034). In AML M0 FAB subgroup of patients the trend to higher P-gp protein expression was observed. CONCLUSIONS: The laboratory methodology to multidrug resistance markers detection was introduced. Some relations between multidrug resistance markers playing role in acute myeloid leukemia patients prognosis were suggested.

[Immunopathogenesis of diabetes mellitus I]. / Imunopatogeneze diabetes mellitus I. typu.

The pathogenesis of diabetes mellitus I is multifactorial. Both genetic predisposition and environmental factors are involved in the deregulation of immune system with subsequent breakage of self-tolerance. Autoantibodies against numerous autoantigens are raised during this long-term process but the principal pathogenic mechanism is cytotoxic killing of beta cells of pancreas mediated predominantly by T cells. There could be the chance to interrupt this pathogenetic process by manipulation with immune system to achieve induction of tolerance. Such clinical trials are now under progress.

Self-calibration of biplanar radiographs for a retrospective comparative study of the 3D correction of adolescent idiopathic scoliosis.

A novel technique for the 3D reconstruction of the spine from X-ray images is presented. The algorithm is based on the self-calibration of biplanar radiographs. It allows the 3D reconstruction of spines from old uncalibrated preoperative and postoperative radiographs. The reliability of the new self-calibration technique was investigated by validating its results against those of the Direct Linear Transform (DLT) on real images. An accuracy experiment was also performed using a dry spine specimen under controlled conditions. The results indicate that self-calibration is a viable technique, accurate enough to extract meaningful 3D clinical data for retrospective studies.

[Apoptosis, its mechanisms and medical significance. I. Definition of apoptosis and its progression at the cellular level]. / Apoptóza, její mechanismy a medicínský význam. I. Definice apoptózy a její prubeh na bunecné úrovni.

Apoptosis is a one example of genetically-regulated cell death. It is characterized by the phylogenetically highly conserved activation of specific genes and proteins followed by energy-consuming proteolytic autodestruction. Apoptosis seems to be physiological and highly selective mechanism to eliminate either old or injured cells in organisms. It is in contrary to mitosis. A highly complex combination of various stimuli both extracellular and intracellular origins is required for induction of apoptosis together with preserved oxidative phosphorylation.

[Apoptosis, its mechanisms and medical significance. II. Disorders of apoptosis regulation and their relation to the development of diseases]. / Apoptóza, její mechanismy a medicínský význam. II. Poruchy regulace apoptózy a jejich souvislost s rozvojem onemocnení.

Study of apoptosis seems to be relevant to clinical medicine nowadays. Dysregulation of apoptosis is under the certain circumstances the cause of various pathological processes in organism. The numerous methods to analyse apoptosis are now well established. It is very likely that our better understanding of apoptosis could lead to improvement in diagnosis and treatment of diseases such as immunopathology, cancer, and others.

[In vivo reduction of radiocesium with modified clinoptilolite in sheep]. / In vivo redukce radiocesia modifikovaným klinoptilolitem u ovcí.

The efficiency of the sorbent prepared by immobilization of [Iron(II)hexacyanoferrate(II)] on clinoptilolite--marked as ZEOFe--in reduction of the radiocaesium Cs-137 has been in vivo investigated in sheep. It was found that an application of this modified clinoptilolite affected both primary and secondary resorption of Cs-137 also by interrupting the enteral cycle of radiocaesium in sheep. It was proved that ZEOFe accelerated approx. twice the excretion of Cs-137 from sheep's body. The whole effect resulted in 15 to 50 times lowering of the equilibrium concentration of radiocaesium in the case of constant intake of the contaminated feed and simultaneous application of 50 grams of ZEOFe daily. The actual reduction depends mainly on the way of administration. The reduction of Cs-137 by non-modified clinoptilolite--ZEO--has been investigated, too. More than 10x lower sorption efficiency has been observed in comparison with ZEOFe.

Induction of growth plate cartilage ossification by basic fibroblast growth factor.

In mammals, longitudinal bone growth results from the precise coupling of chondrogenesis and osteogenesis within the epiphyseal growth plate, a process termed endochondral ossification. The mechanisms coupling chondrogenesis and osteogenesis are unknown. Previous studies have shown that both basic fibroblast growth factor (bFGF) and acidic FGF are expressed by growth plate chondrocytes. Here we show that bFGF, infused directly into the rabbit proximal tibial growth plate, accelerates vascular invasion and ossification of growth plate cartilage. Our results suggest the possibility that bFGF (or a related member of the FGF family) couples osteogenesis to chondrogenesis by attracting vascular and bone cell invasion from the adjacent metaphyseal bone.

Catch-up growth after glucocorticoid excess: a mechanism intrinsic to the growth plate.

In humans and other mammals, the release from growth-inhibiting conditions, such as glucocorticoid excess, leads to supranormal linear growth. The prevailing explanation for this catch-up growth involves a central nervous system mechanism that compares actual body size to an age-appropriate set-point and adjusts growth rate accordingly via a circulating factor. Although such a neuroendocrine "sizostat" was hypothesized more than 30 yr ago, its existence has never been confirmed experimentally. Here we show that suppression of growth within a single growth plate by locally administered glucocorticoid is followed by local catch-up growth that is restricted to the affected growth plate. Thus, the catch-up growth cannot be explained by neuroendocrine mechanism but, rather, must arise from a mechanism intrinsic to the growth plate. To explain this finding, we propose that the normal senescent decline in growth plate function depends not on age per se, but on the cumulative number of stem cell divisions, and that glucocorticoid administration, by suppressing stem cell proliferation, delays senescence, resulting in catch-up growth after the growth-inhibiting agent is removed.

[Influences on radiocesium retention in minipigs]. / Ovlivnení retence radiocesia u miniprasat.

The efficiency of an active substance (AL) prepared in our laboratory as a composite sorbent on the basis of hexacyanoferrates (II) bound on pearl cellulose, in affecting the radiocesium (Cs-137) retention in white miniature pigs was investigated. The function of the composite sorbent in dependence on the way of administration, i.e. its effect on a decrease of primary resorption and its ability to interrupt the enteral cycle was studied, too. The efficiency of stable cesium administration in the form of CsCl in the same process was also determined. It was proved that AL accelerated significantly the excretion through its effect both on primary resorption causing an approx. 11-fold reduction of resorption when administered simultaneously with radiocesium and on the enteral cycle, causing an approx. 3.5-fold increase of excretion of Cs-137 when administered daily. Thus the composite sorbent (AL) administered at long-term along with contaminated feed reduced the equilibrium concentration of radiocesium in meat 30-40 times. This might be of great importance in the time of nuclear emergencies. On the other hand, administration of non-active Cs at a level up to 1 mg Cs/1 kg of liveweight had no significant effect on Cs-137 elimination.