[Fibroblasts--known or unknown cells]. / Fibroblasty--bunky známé ci neznámé?

Fibroblasts form the main component of the cell tissue microenvironment, and their basic function is to maintain cell integrity and tissue homeostasis. Fibroblasts essentially participate in wound repair. Recently, increased interest has been focused on the role of fibroblasts in cancers, where they are involved in the ransformation of a tumour stroma, and via production of numbers of cytokines and growth factors participate in tumour progression. With regard to their impact in cancerogenesis, fibroblasts become a new target of cancer therapy.

[Persisting symptoms, diastolic dysfunction and decreased coronary flow reserve after succesful correction of aortic recoarctation]. / Pretrvávajúce symptómy, diastolická dysfunkcia a nízka koronárna rezerva u pacientky po úspesnej korekcii rekoarktácie aorty.

We present a case of a 53-year-old woman undergoing successful surgical treatment ofcoarcation restenosis after patch grafting in childhood. Despite the optimal result of the operation, normal left ventricle systolic function and coronary angiogram, majority of symptoms, such as angina and dyspnea, persist 16 months after the intervention. In further investigation, pathological values of left ventricular end-diastolic pressure (LVEDP = 30 mm Hg) and coronary flow reserve (CFR = 1.3) were confirmed, implicating recoarctation to be the unusual cause of cardiac syndrome X.

The role of vascular endothelial growth factors and their receptors in malignant melanomas.

Vascular endothelial growth factors (VEGFs) have a leading role among variety of angiogenic factors. Together with their receptors, they play an important role in endothelial cell proliferation and/or elongation, migration and vascular morphogenesis. In order to determine their possible role in malignant melanoma progression, VEGF (representing VEGFA), VEGF-C and VEGFR-1, -2, -3 immunohistochemical expression on formalin-fixed, paraffin-embedded tissue sections were evaluated. A total of 196 tissue samples consisting of 130 malignant melanomas (MM) with various vertical depth of invasion, 15 metastatic melanomas, and 66 nevi including dysplastic nevi and melanocytic nevi were analysed. Production of both VEGFs were common in benign melanocytic tumors while MM exhibited significant upregulation of VEGF (p<0.0027) and VEGF-C (p<0.0001). The proteins were also detected within stromal cells surrounding tumors, particularly in fibrocytes/ fibroblasts, macrophages and endothelial cells. They also exhibited significant increase in malignant lesions (p<0.0001). VEGFRs were localized in tumor, as well in stromal cells. Although expression of VEGF receptors was significantly higher in MM versus nevi (p<0.002 for VEGFR-1, p<0.004 for VEGFR-2 and p<0.0001 for VEGFR-3), a considerable percentage of MM were negative. There were no correlations between sentinel node positivity and all investigated proteins. When clinical outcome was evaluated, progression of the disease positively correlated with VEGF (p<0,007) and VEGF-C (p<0,008) expression VEGF (p<0.001) and VEGF-C (p<0.0001) positively correlated with nestin expression in the capillary endothelium, which was used for angiogenesis detection. Our work demonstrated that upregulation of VEGFs is associated with progression of malignant melanomas. The protein expression in the tumor microenvironment highlights their importance in malignant stromal phenotype which may serve as a potential target for the anticancer therapy.

Comparison of lipid lowering effect of sibutramine in patients treated or not treated with statins--3 month follow-up.

Older sibutramine studies showed beneficial effects on lipid profile compared to placebo. However, nowadays many obese patients are treated with lipid lowering drugs before the start of sibutramine therapy and their effects in these patients have not been investigated. Therefore we started a long-term follow up of patients on sibutramine with or without previous and continuing statins. Here we present results of the first 3 months follow up of 11 patients on sibutramine 10 mg +statin group, and that of 13 patients on sibutramine 10 mg alone. Sibutramine led to the weight loss from 101.6 to 96.9 kg and in BMI from 36.35 to 34.66 kg/m2. Lipid profile changed thus: total cholesterol 4.97...5.01mmol/l (p = 0.7), LDL cholesterol 2.83...2.82 mmol/l mmol/l (p = 0.9), HDL cholesterol 1.13...1.27 mmol/l (p = 0.003), triglycerides 1.98...1.91 mmol/l (p = 0.01). Comparison between the 2 groups did not show any significant differences in lipid levels, patients react to sibutramine in the same way regardless to the concomitant statin therapy. We can therefore preliminarily conclude that sibutramine therapy has significant positive effect on the lipid profile even in patients who were started on statins prior to initiation of sibutramine treatment.

[Residual echocardiographic findings and NT-proBNP in asymptomatic adult patients after radical correction of Fallot's tetralogy]. / Reziduální echokardiografické nálezy a NT-proBNP u asymptomatických dospelých pacientu po radikální korekci Fallotovy tetralogie.

OBJECTIVE: Define the profile of NT-proBNP values in asymptomatic adult patients after radical correction of Tetralogy of Fallot (TOF) and identify links between possible increase in NT-proBNP and residual echocardiographic findings. METHODOLOGY: NT-proBNP samples were taken from and a detailed echocardiographic examination was performed in 21 adult stabilised patients after radical correction of TOF in childhood. The results were submitted for statistical analysis. RESULTS: The incidence of low values of the S wave < 11.5 cm/s of tricuspid anulus evaluated by tissue Doppler echocardiography (TDI) (P < 0.05) was significantly higher in patients with NT-proBNP > 125 pg/ml. All patients with impaired right ventricular diastolic filling evaluated by tissue Doppler echocardiography (E' / A' < 1 ) had higher values of NT-proBNP (NS). Other echocardiographic parametres did not show any dependence on NT-proNBP values, including the morphology or atrial defects in the right heart sections which are most conspicuous in an echocardiographic examination. CONCLUSION: Asymptomatic patients after radical correction of TOF have higher values of NT-proBNP (167.95 +/- 91.75 pg/ml). At the same time, the increase closely correlates with the detection of a global right ventricle systolic dysfunction evaluated by S (TDI). On the other hand, there is often no correlation between highly conspicuous changes in the morphology of the right heart compartments or residual or postincision defects of the pulmonary valve on the one hand and increased NT-proBNP on the other. The S measurement has the potential to become routine examination in patients after radical correction of TOF for timely detection of right ventricular systolic dysfunction. Precise prognostic and primarily therapeutic impact of the pathologic finding still needs to be determined.

[The role of intermedial filament nestin in malignant melanoma progression]. / Význam intermediárního filamenta nestinu v progresi maligního melanomu.

UNLABELLED: Nestin is one of intermedial filaments exprimed in proliferating progenitor cells of the CNS and PNS (central and peripheral nervous system). Postnatal reexpression of the protein occures mainly in CNS tumors and correlates with a high grade of malignancy. The aim of our study is assessment of the nestin expression in benign and malignant skin melanocytic lesions with respect to presume a prognostic role of this protein. We examined 127 bioptic specimens, including 42 nodular melanomas (NM), 32 superficial spreading melanomas (SSM), 10 dysplastic nevi and 43 common intradermal or dermoepidermal nevi. We proved significant increase in nestin expression in melanoma groups, especially in nodular melanomas, where nestin was localized mainly in the peripheral, invasive areas of the tumor mass. CONCLUSION: Detection of nestin expression might be used as an additional melanocytic tumour marker.

Proto-oncogene c-myc in uterine cervix carcinogenesis.

The biological behaviour of precancerous and early stages of uterine cervix carcinoma is not always easily predictable. It is important therefore to identify new biological markers which could more reliably predict the evolution of the disease or provide important therapeutic targets. To establish the role of the proto-oncogene c-myc in uterine cervix tumorigenesis, we examined 96 tissue samples of different degrees of cervical intraepithelial neoplasia (CIN1-CIN 3), in situ (CIS) or invasive squamous cell carcinoma (ISCC) and control cases. Indirect immunohistochemical techniques were used to detect the c-myc expression. Significantly higher levels of Myc protein were found in keratinocytes of high-grade dysplasias in comparison to low-grade dysplasias and control cases. There was no difference between low-grade CIN and a control group of patients. The same significant changes between above mentioned groups were seen in surrounding stromal cells (fibrocytes, fibroblasts, some endothelial cells and lymphocytes). We confirm that expression of c-Myc protein is increased not only in uterine cervix cancer but also in the premalignant lesions. Problem for discussion seems there for whether increased Myc expression in stromal cells might create a more tumor promoting microenvironment which may support the growth and proliferation of transformed cells.

Expression of Bcl-2 in dysplastic and neoplastic cervical lesions in relation to cell proliferation and HPV infection.

Expression of the bcl-2 gene has been shown to effectively confer resistance to programmed cell death in a variety of tumors. The bcl-2 proto-oncogene is involved in the development of human follicular lymphomas and also in a number of solid tumors such as carcinomas of prostate, breast, lung and GIT. The present study was designed to analyze the role of Bcl-2 expression in cervical intraepithelial squamous neoplasias (CIN) and cervical invasive carcinomas. Special attention was given to the association of Bcl-2 expression with the grade of the lesion, proliferative activity (expression of nuclear antigen of proliferative cells - PCNA) and human papillomavirus (HPV) DNA positivity. We examined tissue samples obtained from 86 women with varying degrees of cervical disease. Bcl-2 and PCNA were investigated using immunohistochemical staining and detection of HPV DNA was performed by hybridization in situ. Increased Bcl-2 expression was observed in advanced degrees of dysplasia and in carcinomas. We found a strong association between the presence of Bcl-2 in pathological epithelium with both the degree of dysplasia and the proliferative activity. We also observed a significant correlation between the amount of Bcl-2 positive lymphocytes infiltrating the lesions and the degree of disease. We, therefore, suggest that Bcl-2 expression in these lymphocytes may influence the antiviral or antitumor immune response. On the other hand we did not detect any significant correlation between the Bcl-2 oncoprotein and the presence of HPV. These results indicate that Bcl-2 may play an important role in the development of cervical cancer.

[Pitfalls in the diagnosis of infectious endocarditis]. / Uskalí diagnostiky infekcní endokarditidy.

A group of 63 patients with infectious endocarditis (IE) (1991-1998) was subjected to a detailed retrospective analysis. The authors investigated the age of the patients, site of IE, type of infectious agent, incidence of coinciding diseases or interventions in the close premorbid period of IE, size of vegetation, incidence of embilizations, heart failure, indications for vital early cardiosurgery, number of deaths. From the clinical analysis it may be concluded: 1. There is a new group of patients with IE, who before development of the disease have no manifest cardiac disease who however frequently suffer from another coinciding disease; 2. There is a significant increase of dextrolateral IE (frequently "pacemaker" IE); 3. The ratio of staphylococcal strains in the etiopathogenesis of IE is rising; 4. The mean age of the affected patients is rising (as well as the age scatter); 5. IE is unfortunately frequently diagnosed only after embolization of the vegetation (mostly cerebrovascular attacks) in obscure febrile conditions.

[Restrictive cardiomyopathy as a manifestation of primary amyloidosis]. / Restriktivní kardiomyopatie jako projev primární amyloidózy.

Primary amyloidosis is a rare disease, cardiac involvement occurs in up to 40% of patients. Diffuse amyloid deposits cause an impairment of myocardial systolic and diastolic function. In this paper we are presenting a case of a 54-year-old woman. The woman was admitted because of progressive fatigue, dyspnoea, chest pain, later she experienced hypotension, dyspepsia, and enterorrhagia. ECG showed decrease in QRS amplitude. We have found an echocardiographic evidence of wall hypertrophy. Right cardiac catheterization showed a restrictive situation. Immunobinding of serum and urine revealed monoclonal kappa light chains. The diagnosis was determined by rectal biopsy. Unfortunately, amyloid deposits caused progressive heart failure, hemorrhage, and death just before the diagnosis of primary amyloidosis could be determined on the basis of results of the immunofixations of serum and urine proteins (detection of the monoclonal light chains kappa) and from biopsy specimens taken from rectum (amyloid deposits).

[ST-segment resolution as a simple tool for the assessment of successful primary coronary intervention at a microvascular level]. / Ustup ST elevací jako jednoduchý nástroj pro posouzení úspesnosti primární koronární intervence na mikrovaskuláirní úrovni.

BACKGROUND: The primary success of the coronary artery reperfusion by primary coronary intervention (PCI) is almost angiographically assessed by TIMI flow score. The perfusion at a microvascular level can be inadequate despite the restoring of normal flow in the epicardial coronary artery. One of the options of successful reperfusion at a microvascular level is the measurement of ST-segment resolution (STR) after primary PCI. AIM: The assessment of ST-segment resolution in patients indicated for primary PCI and the comparison with clinical data. METHODS: The authors studied 149 patients (68.5 % men) with ST elevation acute myocardial infarction treated by primary PCI. The ECG was taken at the time of arriving patient at coronary unit and compared with ECG early after primary PCI. Patients were divided into 3 groups according to the grade of STR: with complete (> or = 70%), partial (30-69%) and none (< 30%) STR. The lead with maximal changes (STEmax) and sum of ST elevation (STEsum) were assessed. RESULTS: 42 (28.2 %) patients had complete STR, 55 (36.9%) partial STR and 52 (34.9%) patients didn't achieve STR. STR was connected with better left ventricular ejection fraction, which was in group with complete STR 50% compared with 39.4% in group without STR (p < 0.0001). Patients with symptoms of heart failure on admission (Killip II-IV) had complete STR only in 4 cases (10%) compared with patients without heart failure (Killip I), where was complete STR in 38 (34.8%), (p = 0.003). There wasn't noted significant difference in STR at dependence on glycoprotein IIb/IIIa inhibitors administration. A normal or mildly slower coronary flow (TIMI 2, 3) was achieved in 146 patients (98%), 3 patients (2%) had inadequate coronary flow after primary PCI (TIMI 0, 1). CONCLUSIONS: The evaluation of early ECG changes is simple method for the assessment of primary PCI success at the microvascular level. Our outcomes confirm a differences in achievement of optimal epicardial coronary flow and a perfusion at microvascular level.