Serological and molecular detection of Toxoplasma gondii in farm-reared ostriches (Struthio camelus) in the Czech Republic.

Toxoplasmosis is a globally spread disease, affecting humans and many animal species, including birds. Antibodies to Toxoplasma gondii were detected in ostriches from South and North America, Africa and Asia. Except for one study from Spain, there is a lack of information about T. gondii seroprevalence in ostriches from Europe. For this reason, the aim of the study was to detect antibodies to T. gondii in farm-reared ostriches from the Czech Republic. Serum samples of 409 ostriches (Struthio camelus), collected at 9 farms were tested by Latex agglutination test. Antibodies to T. gondii were detected in 149 (36%) birds with a statistical difference for individual farms (8%-71%, p = 0.0121), and regions (8%-65%, p = 0.002). Seropositivity did not statistically differ (p > 0.05) in size of farms (50% and 35% on small and large farms, respectively), sex of birds (38% and 35% in males and females, respectively), season and year of collection. Tissue samples (brain, heart, and pectoral muscle) of 105 birds were also tested by PCR to detect T. gondii DNA. The parasite T. gondii was detected in the brain and heart of one seronegative ostrich (1%) from a small farm. Based on our results, we can assume that ostriches may present high risk of toxoplasmosis for humans through consumption of raw or undercooked ostrich meat and even seronegative individuals could harbor T. gondii in their tissues. To our knowledge, this is the first serological detection of T. gondii in ostriches in the Czech Republic, and the first PCR detection in Europe.

Prognosis of HPV-Positive and -Negative Oropharyngeal Cancers Depends on the Treatment Modality.

BACKGROUND: The association between human papilloma virus (HPV) and oropharyngeal carcinoma is a topical issue due mainly to the rapid increase in incidence over recent years. These tumors are etiopathogenetically, epidemiologically, and clinically different from other carcinomas at this location. They have a better prognosis in that they are more chemo-and radiosensitive. Indeed, this has been shown by many extensive retrospective and prospective studies. HPV status is considered an integral part of a standard histopathological examination and is included as a new biological parameter in TNM classification. MATERIALS AND METHODS: The results of 77 patients who were treated non-surgically for locally advanced oropharyngeal carcinoma at a single university ear, nose, and throat clinic were analyzed retrospectively. RESULTS: Overall and specific survival of those with HPV-positive (HPV+) tumors was better that those for HPV negative (HPV-) tumors. With the exception of TNM classification, HPV positivity appeared to be the strongest predictor of local control, and of overall and specific survival, regardless of the type of treatment. However, smoking and p53 positivity were significant negative predictors of overall survival. Patients with HPV-associated tumors had a significantly better prognosis, regardless of treatment type. The difference between treatment modalities was confirmed for the whole group of patients, but not for the HPV+ and HPV-patients specifically, most probably due to the small number of patients enrolled. CONCLUSION: The results obtained herein may constitute the first step toward the concept of treatment de-escalation in those with HPV-associated oropharyngeal carcinoma; however, this decision can be based only on the results of current extensive randomized trials. Specification of the optimal de-escalation scheme, or the choice of treatment modality, for which the difference in treatment results is most pronounced, has yet to be identified. This work was supported by grants of the Ministry of Health of the Czech Republic IGA NT12483-4/2011 and AZV 15-31627A. he authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 21. 9. 2018 Accepted: 14. 5. 2019.

Pilot study of A-FABP levels as a predictive factor of SPECT results in asymptomatic relatives of patients with cardiovascular disease.

BACKGROUND: A-FABP is a promising link between metabolic syndrome and atherosclerosis. It is not well known whether level of A-FABP predicts results of SPECT. PATIENTS & METHODS: In 82 subjects (53 males) with a median age of 54 years, who were first-degree relatives of patients with cardiovascular disease, the following tests and examinations were performed: A-FABP, calcium score (CS) and SPECT. RESULTS: Subjects with positive and negative SPECT results differed significantly in the noncategorized CS (p = 0.001), uric acid (p = 0.025) and the total cholesterol:high-density lipoprotein ratio (p = 0.043), but not in other parameters (including A-FABP). To predict SPECT results, the best model proved to be a logistic regression model with gender and noncategorized CS as predictors, with an area under the receiver operating characteristic curve of 0.89 (the sensitivity and specificity based on a CS cutoff of 11.1 were 77.78 and 75.34%, respectively). CONCLUSION: The serum level of A-FABP is not a predictor of a positive SPECT result.

Toxicity and survival outcomes of adjuvant chemoradiation for gastric and gastroesophageal junction cancer patients treated in period 2006-2009: an institutional experience.

Surgical resection is the mainstay of gastric or gastroesophageal junction cancer treatment and has curative potential for patients with early-stage disease. In order to improve the poor survival rates, there are two complementary treatment strategies used at most - perioperative chemotherapy based on UK Magic trial or adjuvant chemoradiation based on INT-0116 trial. Daily treatment decision making should be led also by institutional experiences with toxicity evaluation. We evaluated survival and toxicity outcomes of 47 consecutive patients who underwent adjuvant chemoradiation in our institution in the years 2006-2009. 45Gy in 5 weeks with concurrent two cycles of FUFA Mayo regimen chemotherapy were administrated as part of combined treatment. The acute toxicity was relatively mild (CTCAE scale): grade 2 nausea in 26%, vomiting in 13%, and diarrhoea grade 1 in 15% and general abdominal discomfort in 57% of patients. Grade 3 haematological and infectious complications in 6% and 2% respectively. Late adverse events were as follows: grade 1 esophageal toxicity in 17%, signs of mild chronic esophageal ulceration and esophageal stenosis in 9% of patients (50% of them had tracheoesophageal fistula). The Kaplan- Meier estimate of the median overall survival was 30.5 months with median 25.7 months disease free survival. The overall survival was statistically significantly affected by the amount of removed positive lymph nodes. For the proper evaluation of radiotherapy role in multimodal treatment approach, results of other clinical trials investigating role of concurrent radiotherapy in administration of perioperative chemotherapy will be necessary. Meanwhile, two equally approaches are possible, all having their pros and cons. Institutional toxicity evaluation is recommended in order to provide the best care possible.

Toxicity and survival outcomes of adjuvant chemoradiation for gastric and gastroesophageal junction cancer patients treated in period 2006-2009: an institutional experience.

Surgical resection is the mainstay of gastric or gastroesophageal junction cancer treatment and has curative potential for patients with early-stage disease. In order to improve the poor survival rates, there are two complementary treatment strategies used at most - perioperative chemotherapy based on UK Magic trial or adjuvant chemoradiation based on INT-0116 trial. Daily treatment decision making should be led also by institutional experiences with toxicity evaluation. We evaluated survival and toxicity outcomes of 47 consecutive patients who underwent adjuvant chemoradiation in our institution in the years 2006-2009. 45Gy in 5 weeks with concurrent two cycles of FUFA Mayo regimen chemotherapy were administrated as part of combined treatment. The acute toxicity was relatively mild (CTCAE scale): grade 2 nausea in 26%, vomiting in 13%, and diarrhoea grade 1 in 15% and general abdominal discomfort in 57% of patients. Grade 3 haematological and infectious complications in 6% and 2% respectively. Late adverse events were as follows: grade 1 esophageal toxicity in 17%, signs of mild chronic esophageal ulceration and esophageal stenosis in 9% of patients (50% of them had tracheoesophageal fistula). The Kaplan- Meier estimate of the median overall survival was 30.5 months with median 25.7 months disease free survival. The overall survival was statistically significantly affected by the amount of removed positive lymph nodes. For the proper evaluation of radiotherapy role in multimodal treatment approach, results of other clinical trials investigating role of concurrent radiotherapy in administration of perioperative chemotherapy will be necessary. Meanwhile, two equally approaches are possible, all having their pros and cons. Institutional toxicity evaluation is recommended in order to provide the best care possible. Keywords: adjuvant chemoradiation, gastric cancer, early toxicity, late toxicity, survival outcomes.

[Contribution to the evaluation of serum levels of selected biological parameters in monoclonal gammopathy of undetermined significance and in individual clinical stages of multiple myeloma]. / Príspevek k hodnocení sérových hladin vybraných biologických pusobku u monoklonální gamapatie nejistého výnamu a v jednotlivých klinických stadiích mnohocetného myelomu.

INTRODUCTION: This study aimed to measure serum levels of 12 selected parameters in patients with monoclonal gammopathy of undetermined significance (MGUS) and initial, asymptomatic phase of multiple myeloma (MM) to assess their potential benefit in differentiating both conditions. PATIENT SAMPLE AND METHODOLOGY: The analysed sample of 131 patients consisted of 62 patients with MGUS and 69 patients with MM fulfilling the criteria of the International Myeloma Working Group (IMWG). The following techniques were used to assess serum levels: quantitative immunoradiometry (bone-type alkaline phosphatase - bALP and insulin-like growth factor-1 - IGF-1), chemiluminescent enzyme immunochemical reaction (parathormone--PTH), quantitative sandwich enzyme immunoassay (osteopontin--OPN, endostatin (ES), macrophage inflammatory protein-1alpha/beta--MIP-1alpha/beta, angiogenin--ANG a IL-17). Pearson chi2 test and Mann-Whitney U-test were applied during the statistical analysis. RESULTS: The analysis showed statistically significant differences in serum concentrations between MGUS and symptomatic form of MM (Durie-Salmon (D-S) stage 2-3) for: albumin, beta2-microglobulin (beta2-M) and OPN (p = 0.0001 and < 0.0001); osteocalcin for stage 2 (p = 0.006) and MIP-1alpha for stage 3 patients (p = 0.0002). Using the International Staging System (ISS), statistically significant differences between MGUS and all stages of MM (1-3) were identified for albumin and OPN (p = 0.003 and 0.001 and 0.00009, respectively), stages 2 and 3 for beta2-M and ES (p = 0.015 and 0.0001, respectively), stage 2 for ANG (p = 0.014) and stage 3 for MIP-1alpha (p = 0.00001). Statistically significant differences between MGUS and initial, asymptomatic phase of MM (D-S stage 1) was found only for bALP (p = 0.01) and for albumin (p = 0.004) and OPN (p = 0.003) when ISS was applied. Renal function impairment (D-S substage B) showed in comparison to MGUS significant elevation of serum levels of beta2-M (p < 0.0001), OC (p = 0.011), IGF-1 (p = 0.014), OPN (p = 0.003), ES (p = 0.0001), MIP-1alpha (p = 0.0004) and ANG (p = 0.005) and for albumin (p < 0.0001), beta2-M (p < 0.0001) and OPN (p < 0.0001) only when compared to substage A. CONCLUSION: Only albumin and OPN showed useful even though non-specific potential to differentiate MGUS from all ISS stages of MM, beta2-M and ES for ISS stages 2 and 3, the other parameters differed for stage 2 (ANG), stage 3 (MIP-1alpha) only and stage 1 (bALP), stage 2 (OC) and stage 3 (MIP-1alpha) when D-S stratification was applied.

[Analysis of serum levels of selected biological parameters in monoclonal gammopathy of undetermined significance and multiple myeloma]. / Analýza sérových hladin vybraných biologických ukazatelu u monoklonální gamapatie nejistého významu a mnohocetného myelomu.

BACKGROUNDS: The aim of the study was to evaluate the serum levels of 18 selected parameters in monoclonal gammopathy of undetermined significance, and the initial, asymptomatic phase of multiple myeloma, also from the point of view of the potential contribution to the differentiation of these two units. MATERIALS AND METHODS: The analyzed 119-patient group consisted of 59 individuals with monoclonal gammopathy of undetermined significance and 60 patients with multiple myeloma assessed at the time of diagnosis before the start of the treatment. For the evaluation of serum levels we used radioenzyme assay (thymidine kinase), immunoradiometry (IGF-1), enzyme immunoassay (osteocalcin, osteoprotegerin, ICTP), electrochemiluminiscence (PINP), quantitative sandwich enzyme immunoassay (MIP-1 alpha and MIP-1 beta, IL-17, osteopontin, HGF, VEGF, angiogenin, endostatin, syndecan-1/CD138), and for the assessment of serum levels of free light chains kappa and lambda, the Freelite system. Statistical evaluation was done using the Pearson chi-quadrat test and the U-test according to Mann-Whitney (p < 0.05). RESULTS: Statistically significant differences between monoclonal gammopathy of undetermined significance and multiple myeloma were found in the case of serum levels of thymidine kinase (0.0002), ICTP (0.001), MIP-1 alpha (0.002), osteopontin (<0.0001), HGF (< 0.0001), syndecan-1 (<0.0001), and the kappa/lambda ratio (0.0002), while lower significance was found in the case of angiogenin (0.031) and endostatin (0.011). Statistically non-significant differences between multiple myeloma and monoclonal gammopathy of undetermined significance were within the serum levels of IGF-1, osteocalcin, bALP, PINP, OPG, MIP-1 beta, IL-17, parathormon and VEGF. CONCLUSION: Statistical analysis revealed significant differences between monoclonal gammopathy of undetermined significance and multiple myeloma in 9 of the 18 evaluated parameters. However, due to the significant overlapping of the measured values, none of the parameters is unambiguously able to distinguish between the units. A certain contribution in the discrimination of multiple myeloma from monoclonal gammopathy of undetermined significance was found in markedly increased serum levels of thymidine kinase, MIP-1 alpha, osteopontin, HGF and significant pathology of the kappa/lambda index.

The importance of serum levels of selected biological parameters in the diagnosis, staging and prognosis of multiple myeloma.

The study aimed at evaluating the relation of 7 parameters associated with the internal biological properties of myeloma cells and the bone marrow microenvironment to multiple myeloma (MM) stages, distinguishing its initial/asymptomatic phase from monoclonal gammopathy of undetermined significance (MGUS) and assessing their relation to myeloma prognosis. In the studied group comprising 286 individuals (89 MGUS and 179 MM patients), statistically significant differences (Mann-Whitney test) between MGUS and MM at the time of diagnosis were found in the serum levels of HGF (hepatocyte growth factor), VEGF (vascular endothelial growth factor), ICTP (intercellular - carboxy-terminal telopeptide of type I collagen), PINP (procollagen type I N-terminal propeptide), OPG (osteoprotegerin) and syndecan-1/CD138, but not in Fas. Multivariate analysis (logistic regression) revealed an unsatisfactory potential of all the 7 studied indicators to discriminate between MGUS and MM. A deeper analysis showed statistically significant differences between MGUS and the initial/asymptomatic phase of MM (stage 1 according to the International Staging System) only in the cases of syndecan-1 (p=0.001) and Fas (p=0.008). The assessment of initial values of HGF, VEGF, ICTP, PINP, OPG, syndecan-1 and Fas showed a statistically significant relation (log rank test) to the overall survival (OS) in a group of 132 patients treated with conventional chemotherapy only in the cases of syndecan-1 (p=0.0002) and Fas (p=0.018), but in none of the investigated parameters in a group of 74 patients treated with HDT/ASCT (high-dose therapy/autologous stem cell transplantation). The analysis showed that, despite significant differences in serum levels of 6 of the 7 studied parameters found between MGUS and MM, none of the markers may be included in the spectrum of indicators used to distinguish the two conditions. Despite the positive relation, especially of syndecan-1 and, to a lesser extent, of Fas to the OS in patients treated with conventional chemotherapy, these prognostic factors are not applicable to HDT/ASCT.

[Risk stratification by cardiac gated SPECT combined with coronary artery calcium score in patients with diabetes mellitus and/or renal failure]. / Stratifikace rizika pomocí zátezového SPECT zobrazení myokardu v kombinaci se stanovenim koronárního kalciového skóre u rizikových pacientu s diabetem a/nebo ledvinným selháním.

AIM: The aim of this study was to evaluate added value of coronary artery calcium score (CAC) measurement as an adjunct to cardiac gated SPECT for risk stratification in population of patients with diabetes mellitus (DM) and/or chronic renal failure on hemodialysis (CHRF-HD). METHODS: Retrospective analysis of 67 patients, who were referred for stress gated myocardial perfusion SPECT and CAC. Characteristics of study population: 40 men, mean age 59 +/- 12 years, DM (n = 28), CHRF-HD (n = 22), DM and CHRF-HD simultaneously (n = 17). Perfusion summed stress and different scores (SSS, SDS), the left ventricle ejection fraction (LVEF) and enddiastolic/endsystolic volumes (EDV/ESV) were automatically calculated using 4D-MSPECT software. The hard cardiac event was defined as sudden cardiac death or myocardial infarction (MI); angina or other symptoms requiring coronary revascularization were also calculated. RESULTS: During the average period of 18 +/- 10 months, we registered 8 cardiac deaths, 4 nonfatal MI and 7 patients underwent revascularization. In the subgroup of 19 patients with cardiac events, the observed parameters were significantly worse concerning perfusion (SSS 9 +/- 11 vs 2 +/- 3 and SDS 6 +/- 9 vs 1 +/- 2, P < 0.05), the left ventricle function (stress LVEF 53% +/- 13% vs 59% +/- 13%, rest LVEF 55% +/- 14% vs 59% +/- 12%, stress EDV/ESV 144 ml/71 ml vs 128 ml/59 ml, P < 0.05), and CAC score (1 965 +/- 1 772 vs 387 +/- 740, P < 0.05) in comparison with patients without cardiac event. In patients without a reversible perfusion abnormality (SDS < 2), we observed lower annual hard event rate (8% vs 19.6%, P < 0.05) and revascularization procedures (4% vs 19.6%, P < 0.05) in comparison with patients with SDS > or = 2. In patients with or without reversible defects, we registered significantly higher annual hard event rate in the setting of post-stress worsening of the LVEF > 5% and/or severe CAC score > or = 709 (23.8% vs 1.9% in patients with SDS < 2, and 26.7% vs 9.5% in patients with SDS > or = 2, P < 0.05). CONCLUSION: The findings of highly elevated CAC score as well as the post-stress left ventricle stunning enable further risk stratification in patients with or without reversible perfusion abnormalities.

[The comparison of serum levels of selected biomarkers in monoclonal gammopathy of undetermined significance and multiple myeloma]. / Srovnání sérových hladin vybraných biologických pusobku u monoklonální gamapatie nejistého významu a mnohocetného myelomu.

BACKGROUND: The aim of the study was the evaluation of serum levels of 12 selected biomarkers in monoclonal gammopathy of undetermined significance (MGUS) and in initial, asyptomatic phase of multiple myeloma, especially from the view of potential differentiation of these conditions in clinical practice. METHODS AND RESULTS: Analyzed group of 268 individuals consisted of 89 individuals with MGUS and 179 patients with MM examined in time of diagnosis before treatment initiation. For evaluation of serum levels were used following methods: radioenzymatic method (thymidinekinase), enzymatic immunoassay (beta2-M, IL-6R, ICAM-1, VCAM-1, ICTP, PINP and OPG) and quantitative sandwich enzymatic immunoassay (HGF, VEGF, syndecan-1/CD138 and Fas). Pearson's chi2-test and test according to Mann-Whitney were used for statistical evaluation (p < 0.05). Wide statistic differences in serum levels of analyzed markers in MGUS vs. MM were detected in case of beta2-M, TK, ICTP, OPG, HGF and syndecan-1 (p < 0.0001), lower differences in case of VCAM-1, PINP and VEGF (p = 0.003, 0.001 and 0.04), and without difference in case of Fas. Except for thymidinekinase (p = 0.014) and syndecan-1 (p = 0.001) was not detected statistically important contrast of measured values in MGUS individuals and in patients with initial, asymptomatic phase of MM (stage 1), but these markers cannot be used in clinical practice due to significant overlap of serum values. Continuous downgrade of serum values of VEGF due to degree of MM progression (stages 1-3 according to Durie-Salmon) was unexpected. RESULTS: Although the significant differences in 9 of 12 evaluated serum levels of selected biomarkers in groups of MGUS and MM were seen, the results revealed that these markers are unprofitable to bring discriminatory potential capable of being used to distinguish between MGUS and initial, asymptomatic phase of MM.

Brachial endothelial function in subjects with familial combined hyperlipidemia and its relationships to carotid artery intima-media thickness.

AIM: The aim of this study was to quantify the flow-mediated dilatation (FMD) of brachial artery in asymptomatic members of families with familial combined hyperlipidemia (FCH) and to determine the relation between FMD and risk factors accompanying FCH. We also investigated the association between FMD and the intima-media thickness (IMT) of the common carotid artery. METHODS: Eighty-two members of 29 FCH families were divided into two groups: probands and hyperlipidemic first-degree relatives (HL) (n=47) and normolipidemic first-degree relatives (NL) (n=35). The control (C) groups, C-HL (n=20) and C-NL (n=20), consisted of sex- and age-matched healthy individuals. FMD was assessed in the brachial artery by measuring the change in brachial artery diameter in response to reactive hyperemia. RESULTS: Both hyperlipidemic subjects and their NL had significantly lower FMD (3.4+/-3% vs 6.3+/-2.8%, P<0.001, 5.2+/-2.3% vs 7.8+/-2.8%, P<0.01, respectively) compared to controls. In multivariate backward stepwise regression analysis, FMD in members of FCH families was independently associated with sex (P<0.001), age (P<0.01), C-peptide (P<0.05) and borderline with glycemia (P=0.052). FMD correlated inversely with IMT in all subjects of FCH families and in hyperlipidemic members. In multivariate backward stepwise regression analysis this relation remained independent (P<0.001, P<0.01, respectively). CONCLUSIONS: Members of FCH families showed impaired FMD, which was independently associated with markers of insulin resistance. FMD and IMT were independently associated in hyperlipidemic, but not in normolipidemic members of FCH families.

International prognostic index (IPI)--a critical comparison with five multiple myeloma staging systems in the group of 270 patients treated by conventional chemotherapy.

In the group of 270 patients with multiple myeloma (MM) treated during 1991-2004 by conventional chemotherapy, the prognostic value and practical utility of IPI (International Prognostic Index) was assessed and compared with five other actual staging systems. Prognostic significance was assessed using the curves of overall survival (OS) according to Kaplan-Meier and log rank test (p<0.05). Good practical utility and prognostic significance of Durie-Salmon (D-S) system was confirmed (p<0.001). Good overall prognostic significance was observed in simple staging systems based on the measurement of beta2-microglobulin and albumin serum levels according to Bataille (p<0.001), SWOG (South West Oncology Group, p<0.001) and IPI (p<0.001). Regardless of a short 5-year duration of the study, the scoring system according to San Miguel enclosing apart from other parameters also propidium iodide proliferation index (PC-PI) of myeloma plasmocytes seems to be promising with very different characteristics of curves of overall survival (p<0.001). Very good prognostic value and easy practical utility were examined in Olomouc staging system (OSS) based on the measurement of beta2-microglobulin and thymidinekinase serum levels (p<0.001). With regard to detection of patients of stage 1, i. e. "low risk", not requiring an immediate initiation of conventional chemotherapy ("wait and see" approach), the most suitable was the system according to D-S, SWOG and IPI (median OS 77, 76 and 77 months). To select a cohort of "high risk" patients, i.e. stage 3, with very unfavourable disease prognosis, the most advantageous was the system OSS and San Miguel (median OS was 5 and 6 months) and/or SWOG system selecting patients of stage 4, i.e. "worst prognosis", with median OS 8 months. It was found that IPI did not meet expectations for effective identification of "high risk" patients (median OS of stage 3 was 20 months) nor for the distinction of different prognosis of patients during initial 25 months of MM course at stage 2 vs. 3. The study indicates that under conditions of common clinical practice and conventional chemotherapy, the staging system according to D-S is still useful, while practical application of SWOG and IPI as simpler alternative to the assessment of clinical stage should be verified by further comparative studies. In harmony with the progress in cytogenetics and molecular biology as well as a prospective requirement of individual target therapy, a future suitable stratification system should be based on parameters of internal biological properties of myeloma tissue and microenvironment of bone marrow, allowing in addition a continuous evaluation of the disease course and the effect of therapy.

[Comparison of serum levels of selected biological parameters in monoclonal gammopathy of undetermined significance and multiple myeloma]. / Srovnání sérových hladin vybraných biologických ukazatelu u monoklonální gamapatie nejistého významu a mnohocetného myelomu.

PURPOSE OF STUDY: The study focuses on evaluation of differences in serum levels of selected biological indicators in monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM), primarily from the viewpoint of potential asset to clinical practice. PATIENTS AND METHODOLOGY: The analyse set of 96 patients consisted of 30 individuals with MGUS and 66 patients with MM examined in the context of the disease diagnosis before therapy commencement. Serum levels of the assessed parameters were examined with the help of radio-enzymatic method (thymidinkinase), radioimmunoanalysis (beta2-micro-globulin, ICTP, PINP), enzymoimmunoessay method (sIL-6R, sVCAM-1, sICAM-1, sOPG and sRANKL) and the technique of quantitative sandwich enzymatic immunoessay (sHGF, sVEGF, bFGF, syndecan-1/CD138 and sFas). Statistical examination was performed by Pearson and Fischer test, chi2-test, or nonparametric U-test pursuant to Mann-Whitney (p < 0.05). RESULTS: Statistically significant differences were found between MGUS and MM in the case of serum level comparisons of sIL-6R (p = 0.02), ICTP (p = 0.001), sHGF (p = 0.001) and syndecan-1/sCD138 (p = 0.001), while no statistically significant differences were present in the case of sVCAM-1, sICAM-1, PINP, sOPG, sVEGF and sFas. During the analysis of frequency of occurrence of abnormal values in the MM and MGUS groups, significant differences were found not only in the case of standard parameters, such as beta2-microglobulin, thymidinkinase, creatinin and albumin, but also in the case of sIL-6R, ICTP, sHGF and syndecan-1, but not in comparisons of the levels of sVCAM-1, sICAM-1, PINP, sOPG, sVEGF and sFas. Attempts at examination of serum levels of sRANKL and soluble form of bFGF failed as too low values were measured. CONCLUSION: The analysis of behaviour of the 10 parameters, mostly intimately related to biological properties of clonal plasmatic cells or to changes of microclimate of bone marrow, effectively contributed to distinction between MGUS and MM only in the case of serum levels of sIL-6R, ICTP, sHGF and syndecan-l (sCD138), i.e. indicators with demonstrable relevance for MM prognosis assessment.

[Contribution to the evaluation of the relationship between angiogenic cytokines, selected biological parameters and prognostic factors in multiple myeloma]. / Príspevek k hodnocení vztahu angiogenních cytokinu a vybraných biologických ukazatelu k prognostickým faktorum mnohc'etného myelomu.

BACKGROUND: Multiple myeloma is an unusually heterogeneous disease with individually different clinical course, sensitivity to therapy and prognosis. The undoubted limitation of contemporary diagnostic stratification systems is the insufficient credit of those parameters that express the intrinsic biological properties of myeloma cells and the microenvironment of the bone marrow. The aim of this study was to evaluate the relationship of 10 biological parameters to 6 fundamental prognostic factors of multiple myeloma. METHODS AND RESULTS: The analysed group consisted of 66 individuals examined at the time of diagnosis before the start of therapy. For the estimation of serum levels of investigated molecules there were used following methods: REA RIA, ELISA and the technique of quantitative sandwich enzyme immunoassay. For the analysis of proliferative and apoptotic properties of myeloma cells we used propidium iodide (PC-PI) and annexin-V (PC-AI) indices. The statistical estimation was carried out with the help of Pearson and Spearman test, eventually with the help of U-test according to Mann-Whitney. Increased incidence of abnormal serum levels of examined parameter was registered in the case of S-beta2-microglobulin (95.5%), S-thymidinekinase (57.5%), S-sVCAM-1 (78.5%), S-ICTP (87.0%), S-solubile osteoprotegerin (sOPG 76.5%), S-sSyndecan-1 (56.5%) and low index of plasma cell apoptosis (PC-AI, 78.0%). The statistical analysis (Pearson's test) revealed the mutual relationship of serum levels of: S-beta2-microglobulin to sVCAM-1, (r = 0.39, p = 0.002), sICAM-1 (r = 0.33, p = 0.011), sOPG (r = 0.53, p = 0.001), sHGF (r = 0.34, p = 0.006), sSyndecan-1 (r = 0.38, p = 0.003) and sFas (r = 0.42, p = 0.001); S-albumin to sVCAM-1 (r = -0.29, p = 0.036), ICTP (r = -0.33, p = 0.016), sOPG (r = -0.63, p = 0.000), sHGF (r = -0.39, p = 0.003), sSyndecan-1 (r = -0.29, p = 0.042); S-thymidinekinase to sSyndecan-1 (r = 0.46, p = 0.000) and sFas (r=0.29, p = 0.019). There was no relationship of PINP and VEGF to any of the evaluated prognostic factors. There was no relationship found between either of the analysed parameters to PC-PI and PC-AI. With the help of U-test there was found the relationship of sIL-6R to S-beta2-microglobulin (p = 0.001), albumin (p = 0.002) and PC-PI (p = 0.046). CONCLUSIONS: The presented study implies that the traditional algorithm of parameters used in clinical practice for individual characteristics of MM should be enriched with sOPG, sHGF, sSyndecan-1 and sFas.

[Adjuvant radiotherapy in the therapy of uterine cancer in the first clinical stage]. / Adjuvantní radioterapie v lécbe karcinomu delozního tela 1. klinického stadia.

OBJECTIVE: The aim of our study was to find the influence of the postoperative radiotherapy on local control and overall survival in patients with carcinoma of the uterus. Endometrial carcinoma is the most frequent gynecologic malignity. Surgery, radiotherapy, chemotherapy and hormonal therapy are used in the treatment of this disease. The optimal cure strategy has not been established yet. DESIGN: Retrospective study. SETTING: Department of Radiation Oncology, Masaryk Memorial Cancer Institute, Brno. METHODS: We followed up 246 patients with the diagnosis of endometrial carcinoma. All patients were in clinical stage 1. Median of the age was 60 years. Every patient underwent radical hysterectomy and adnexectomy. Most of them had adjuvant radiotherapy. Combined radiotherapy was used (external beam radiotherapy and brachyradiotherapy). Some of patients underwent only external beam radiotherapy, other had only brachytherapy. We used Kaplan-Meier survival function and methods of Statistica. RESULTS: The median of the follow up was 8.3 years. Local recurrence was proved in 16 cases. The time to the local relapse was 3.2 years. Dissemination occurred in 12 patients. The time to the progression was 5.9 years. Five-year DFS was 80.9%, five-year overall survival was 82.9%. Patients, who had risk factors, were proved to suffer from worse overall survival. The adjuvant radiotherapy improved the local, and the distant control in the group of patients with risk factors. CONCLUSION: The influence of the radiotherapy on the local control was proved in many studies, the influence on the overall survival was not statistically significant. Temporally there is the option not to apply adjuvant radiotherapy. Our study shows the important benefit of the adjuvant treatment in cases of endometrial carcinoma and risk factors.

[Neopterin and a soluble interleukin-2 receptor in patients with systemic lupus erythematodes]. / Neopterin a solubilní receptor interleukinu-2 u nemocných se systémovým lupus erythematodes.

Goal of this study was to monitor levels of serum neopterin and soluble interleukin-2 receptor (sIL-2r) and to evaluate their importance in monitoring activity of systemic lupus erythematodes (SLE). Levels of serum neopterin, anti-dsDNA antibodies, C3, C4 complement components, nucleosomes antibodies, IL-10, fas ligand, soluble thrombomodulin, sVCAM-1, and sICAM-1 were measured in a group of 52 patients with SLE. Positive correlations were proved between neopterin concentrations and disease activity (ECLAM), levels of sVCAM-1, sICAM-1, sIL-2r and thrombomodulin, further between sIL-2r level and disease activity (ECLAM), and concentrations sVCAM-1, sICAM-1 and neopterin. Higher values of neopterin and sIL-2r levels were identified in patients with lupus nephritis compared to patients without kidney impairment. Statistically significant differences were identified in levels of neopterin between a subgroup (A) with minimum disease activity and a subgroup (B) with increasing disease activity (p = 0.01) and a subgroup (C) with decreasing disease activity (p = 0.003 ) and a subgroup (LN) with lupus nephritis (0.007) during the first and the third series of measurements. sIL2r levels which had in all subgroups very varied values were the lowest in the subgroup A with minimum disease activity during the whole time of monitoring. The highest levels reached the free receptor IL-2 in the subgroup B with increasing disease activity and in the subgroup with lupus nephritis. Statistically significant differences in values were identified between the subgroup A (non-active) and the subgroup LN (lupus nephritis) with p = 0.01 during the first set of the measurements. Fluctuation of sIL-2r levels in individual subgroups during the time of monitoring did not reach statistically important levels. In conclusion it could be said that potential practical utilization of the measurement of concentrations of the two mentioned molecules should be seen especially in monitoring disease activity because they don't contribute to SLE with needed information. Their always low values have favourable prognostic impact in monitoring patients with SLE and vise versa.

[Endothelial dysfunction in a family with familial combined hyperlipidemia]. / Endoteliální dysfunkce u clenu rodin s familiární kombinovanou hyperlipidémií.

Familial Combined Hyperlipidemia is the most frequent familial hyperlipidemia with a high risk a early manifestation of arteriosclerosis. Endothelial dysfunction is the first step in the development of arteriosclerosis. The aim of our investigation was to examine selected markers of endothelial dysfunction in hyperlipidemic members of families with familial combined hyperlipidemia and their normolipidemia first-line relatives and to compare them with healthy individuals. The study includes non-smoking members of the affected families (probands and first-line relatives), who have not suffered from clinical manifestations of arteriosclerosis and/or hypertension during the start of the study. The cohort was divided into hyperlipidemic individuals (N = 25) and normolipidemic individuals (N = 21). Both groups were compared with control groups of healthy individuals (two groups, N = 17 each), who were adjusted by age and sex. The following markers of endothelial dysfunction were examined: 1. ultrasound--flow mediated dilatation of brachial artery and 2. humoral--serum levels of von Willebrand factor, inhibitor of activator of plasminogen-1 and vasoadhesive molecules (vascular cell adhesion molecule-1, intercellular adhesion molecule-1). The members of families with familial combined hyperlipidemia displayed symptoms of endothelial dysfunction. In comparison with healthy controls the endothelial dysfunction was more expressed in hyperlipidemic individuals. They displayed a significantly lower flow-mediated dilatation of brachial artery (3.6 +/- 3.3% versus 6.6 +/- 2.8%, P < 0.01), higher levels of von Willebrand factor (152.8% +/- 79.1% versus 110.4% +/- 24.8%, P < 0.05), inhibitor of activator of plasminogen-1 (94.6 +/- 30.8 ng/ml versus 60.4 +/- 38.0 ng/ml, P < 0.01) and vasoadhesive molecules: vascular cell adhesion molecule-1 (927.0 +/- 167.7 ng/ml versus 814.7 +/- 171.1 ng/ml, P < 0.05), intercellular adhesion molecule-1 (601.7 +/- 89.5 ng/ml versus 544.8 +/- 59.8 ng/ml, P < 0.05). The normolipidemic individuals displayed only a significantly lower flow-mediated dilatation of brachial artery (5.6 +/- 2.6% versus 7.5 +/- 2.8%, P < 0.05) and higher levels of von Willebrand factor (136.8 +/- 40.32% versus 104.1 +/- 24.9%, P < 0.05). No significant difference was found in the levels of inhibitor of activator of plasminogen-1 and vasoadhesive molecules. The results indicated that members of families with familial combined hyperlipidemia represent a high-risk group from the standpoint of early manifestation of arteriosclerosis.

[Does grapefruit juice increase the bioavailability of orally administered sex steroids?]. / Zvysuje grapefruitová stáva dostupnost orálne podaných sexuálních steroidu?

OBJECTIVE: To verify if and to which extent the interaction with grapefruit juice can increase bioavailability of orally administered sexual steroids. DESIGN: Pilot pharmacokinetics study. SETTING: Department of Obstetrics and Gynecology and Institute of Pharmacology, Medical Faculty, Palacký University, Olomouc; Department of Nuclear Medicine, University Hospital, Olomouc. METHODS: 2 mg of estradiol valerate and 100 mg of micronized progesterone were given to eight healthy postmenopausal volunteers. Blood samples were collected at time 0, 2, 3, 5 and 24 hours after tablets application. The same trial was repeated a week later but tablets were swallowed with 200 ml of grapefruit juice. Serum levels of estradiol and progesterone were measured by RIA. Results were statistically evaluated using the Wilcoxon's nonparametric paired test. RESULTS: Though grapefruit juice on average slightly increased serum levels of estradiol (E2) and progesterone, this increase reached statistical significance only for the E2 level 24 hours after application of tablets. The mean area under curve (AUC) of estradiol rose significantly to 117%. The even greater increase in the mean AUC of progesterone (to 125%) was not statistically significant because of marked individual variability of response. CONCLUSIONS: Our results suggest that grapefruit juice may increase bioavailability of orally administered estradiol and progesterone. The response varies markedly between individuals. This observation may be of some importance also for users of OC and HRT.

Treatment of uterine sarcoma. A survey of 49 patients.

PURPOSE: Surgery, radiotherapy and chemotherapy are employed in the treatment of uterine sarcoma. We claim to evaluate the role of radiotherapy in the treatment of uterine sarcoma. PATIENTS AND METHODS: We report a retrospective study of 49 patients with uterine sarcoma treated from 1990-1999 at Masaryk Memorial Cancer Institute in Brno. All 49 patients had surgery, 19 (38.7%) had adjuvant radiotherapy and 25 (51%) had chemotherapy. Using the FIGO classification: 71.4% had stage I, 6.1% stage II, 16.3%, stage III and 6.1% stage IVa disease. 42.9% of tumors were mixed Müllerian tumors, 34.7% leiomyosarcomas and 22.4% endometrial stromal sarcomas. 12 cases (24.5%) had a local recurrence, 7 (14.3%) had hematogenous dissemination. There was an increased disease free interval (DFI) for patients treated with adjuvant radiotherapy (p = 0.005). The DFI was favourably influenced by the stage of the disease. Of 12 patients with a local recurrence only one had postoperative radiotherapy. Radiotherapy had an impact on overall survival (OS). The five-year OS probability was 51.6% without radiotherapy and 88.9% with radiotherapy (p = 0.0066). CONCLUSION: We conclude that postoperative radiotherapy in our series of patients diagnosed with uterine sarcoma has an impact on locoregional and disease-free progression intervals (LRFI, DFI) and overall survival (OS). The most important prognostic factor is the extend of the disease (stage). Stage I patients have a significantly better survival.

Clinical utility of selected disease activity markers in patients with systemic lupus erythematosus.

The objective of this study was to assess the utility of measurement of thrombomodulin, antinucleosome antibodies, sVCAM-1, sICAM-1, neopterin, fas ligand, IL-10 and sIL-2R in patients with systemic lupus erythematosus (SLE) and to compare them with traditional markers of SLE activity (anti-dsDNA antibodies, C3, C4) and the ECLAM index of disease activity. The measurement was performed over a 6-month period at three consecutive time points after 3 months in each of the 52 patients with SLE. Anti-dsDNA antibodies, thrombomodulin, antinucleosome antibodies, sVCAM-1m sICAM-1, neopterin, fas ligand, IL-10 and sIL-2R were tested by ELISA technique, while C3, C4 components of complement were tested by nephelometry. Fas ligand and IL-10 did not correlate with the ECLAM index. The rest of the markers showed significant correlation with the disease activity index. Thrombomodulin and anti-dsDNA antibodies reflect in the best way the changing trend in disease activity. Antinucleosome antibodies seem to be a promising marker useful in early diagnosis. Soluble VCAM-1, sICAM-1, neopterin and sIL-2R are interesting molecules with a role in disease pathogenesis, but their practical utility is limited.