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Biomedical subjects

M Tichý

Publications and source records attributed to M Tichý.

At least 19 recordsLinked to original sources

Human urine certified reference material CZ 6010: creatinine and toluene metabolites (hippuric acid and o-cresol) and a benzene metabolite (phenol).

A reference material for the biological monitoring of occupational exposure to toluene, benzene and phenol was prepared. O-cresol and hippuric acid (metabolites of toluene) are used for the biological monitoring of occupational exposure to toluene. Phenol, a metabolite of benzene, is used for the biological monitoring of exposure to benzene, but phenol can of course also be used as an indicator of exposure to phenol as well. The reference material (RM) used for the determination of these metabolites was prepared by freeze-drying pooled urine samples obtained from healthy persons occupationally exposed to toluene and those taking part in an inhalation experiment. Tests for homogeneity and stability were performed by determining urine concentrations of o-cresol, hippuric acid, creatinine and phenol. To investigate the stability of the RM, the urinary concentrations of o-cresol and phenol were monitored for eighteen months using GC and HPLC, while those of hippuric acid and creatinine were followed for five and six years, respectively, using HPLC. Analysis of variance showed that the concentrations did not change. The certified concentration values (and their uncertainties) of the substances in this reference material (phenol concentration c=6.46+/-0.58 mg l(-1); o-cresol concentration c=1.17+/-0.15 mg l(-1); hippuric acid concentration c=1328+/-30 mg l(-1); creatinine concentration c=0.82+/-0.10 g l(-1)) were evaluated via the interactive statistical programme IPECA.

Benzene↗

The significance of soluble CD138 in diagnosis of monoclonal gammopathies.

Report is summary of the results of study designed to ascertain the significance of soluble CD138 (sCD138) assessment in patients with different monoclonal gammopathies. Previous studies have shown that sCD138 is shed from the surface of myeloma cells into serum and that this marker is a new independent prognostic parameter in multiple myeloma. In presented study was evaluated serum sCD138 level in 14 patients with monoclonal gammopathy of undetermined significance (MGUS) and in 17 patients with multiple myeloma (MM), all MM patients were treated by high-dose chemotherapy regimen with subsequent autologous transplantation of peripheral blood stem cells. To determine the sCD138 level we used a rapid and simple ELISA procedure. The mean serum sCD138 level of patients with MGUS was 32 ng/ml (range: 5-128). Soluble CD138 levels were elevated in the sera of 10 out of 17 (59%) multiple myeloma patients, the mean baseline sCD138 concentration was 1542 ng/ml (range: 10-17300). In spite of small number of patients the difference between MGUS and MM group was highly statistically significant (p<0.001). Multiple myeloma patients with high level of sCD138 at diagnosis (cut-off value: 500 ng/ml) had worse prognosis despite of good response to chemotherapy in some of them (p=0.029). It seems that determination of sCD138 can be recommended as a helpful and reliable marker for differential diagnosis as well as prognosis of monoclonal gammopathies.

Biomarkers↗

[Bone marrow angiogenesis in patients with multiple myeloma as a marker of biological behaviour].

Angiogenesis, the creation of new blood vessels from preexisting vascular nets, plays a major role in the development, progression and dissemination of solid malignant tumors. Research over the last few years has shown a correlation of angiogenesis and the biological behaviour of haematologic malignancies. This study focused on the relation of vasoformation, stage of differentiation of tumour plasmocytes and type of bone marrow infiltration in patients with multiple myeloma (MM) prior to treatment. We evaluated trephine biopsy samples from 55 patients for microvessel density in 1 mm2 field by monoclonal antibody anti CD34. Angiogenesis correlated with the type of infiltration and with stage of morphological differentiation. It was highest in the nodular type of infiltration with a low level of differentiation, and lowest in grade 1 differentiation with an interstitial type of infiltration.

Aged↗

International Staging System required standardization of biochemical laboratory testing in multiple myeloma.

The standardization of biochemical measurement procedures in multiple myeloma is necessary for reliable prognostic stratification of patients in multicentric trials. The new prognostic index International Staging System for multiple myeloma uses only two laboratory markers, albumin and beta-2 microglobulin. Our study compared results of albumin, beta-2 microglobulin and monoclonal immunoglobulin measurements from six centers which provide treatment for multiple myeloma in the Czech Republic and attempted to standardize the analytic procedures. We have found that the measurement of albumin is well standardized and the results from all laboratories were comparable. The measurement of beta-2 microglobulin achieved comparability only after a partial unification of analytical methods. The determination of monoclonal immunoglobulin concentration provided comparable results for concentrations higher than 20 g/l with higher variability for lower values.

Antibodies, Monoclonal↗

[Contemporary view on the plasma natriuretic peptide assessment in the clinical practice].

Plasma natriuretic peptide assessment became a part of the routine clinical practice because of the laboratory methods development. After a brief historical overview of natriuretic peptides discovery, the article focuses on the brain natriuretic peptide (BNP). BNP plays an important role in the pathophysiology of many diseases of cardiovascular system due to its effects on the circulation (natriuresis, diuresis, inhibition of renin-angiotensin system, etc). The authors describe process of BNP synthesis, factors leading to its release into circulation. The main emphasis is done on the clinical significance of BNP and NT-proBNP assessment for the-diagnosis in cardiovascular diseases, risk stratification and monitoring of the treatment.

Biomarkers↗

[Ischemia-modified albumin: new marker of myocardial ischemia?].

The Albumin Cobalt Binding Test is a quantitative in vitro diagnostic test used on human serum that detects ischemia-modified albumin by measuring the cobalt binding capacity of albumin in human serum. Ischemia modified albumin is intended for use in conjunction with ECG and cardiac troponin as an aid to short term risk stratification of patients presenting with chest pain suggestive of cardiac origin. Thus, in patients with chest pain or equivalent symptoms suggestive of cardiac origin, with non-diagnostic ECG and normal troponin, a negative IMA can be used as an aid to rule out acute coronary syndrome (ACS) in low risk patients.

Biomarkers↗

The use of biochemical markers in cardiotoxicity monitoring in patients treated for leukemia.

Cardiotoxicity is a serious and relatively frequent complication of anti-tumorous treatment. Anthracyclines represent the greatest risk. Biochemical markers of structural and functional myocardial damage have been gaining ground in cardiotoxicity monitoring. The aim of the study was to monitor cardiotoxicity of induction chemotherapy in acute myeloid leukemia (AML) patients and to assess the potential for use of biochemical markers in early diagnostics of cardiotoxicity. Fifteen consecutive adult patients with a newly diagnosed AML were studied. All patients received induction chemotherapy containing Idarubicin (IDA) 3 x 12 mg/m2 and intermediate doses of Cytarabine (8 x 1.5 g/m2). Serial measurements of plasma N-terminal pro brain natriuretic peptide (NT-proBNP) values were performed at the baseline, the day following each IDA infusion, after 14 days and after circa 1 month, i.e. before the next chemotherapy. Cardio-specific markers (cTnT, CK-MB mass) were measured at the baseline and after the last IDA infusion. The mean baseline value of NT-proBNP in newly diagnosed AML patients was 129.7+/-59.6 pg/ml. The mean NT-proBNP value increased after the first IDA infusion to 307.3+/-171.4 pg/ml (p=0.02). In most of the patients, the second and the third IDA infusions were not associated with a further increase in the NT-proBNP value and levels after 2 and 4 weeks were not significantly different from the baseline. However, in one of the patients the NT-proBNP values were increasing after each IDA infusion (after the last one 786.2 pg/ml) and within 14 days he developed congestive heart failure due to left ventricular diastolic dysfunction as assessed by echocardiography. At that time, the NT-proBNP value was 1,184.0 pg/ml; after diuretics it decreased significantly. In all patients, plasma cTnT and CK-MB mass concentrations were within the reference interval at the baseline and after the induction chemotherapy. Our results suggest that induction chemotherapy in AML (IDA 36 mg/m2 and intermediate doses of Cytarabine): 1. does not cause detectable damage of the myocyte structure, 2. is in all patients associated with acute neurohumoral activation (transient elevation of NT-proBNP) indicating acute subclinical cardiotoxicity, 3. may lead to congestive heart failure and NT-proBNP seems to be a promising early marker and predictor of this complication.

Acute Disease↗

[Treatment results of Langerhans cell histiocytosis with LSH II protocol].

BACKGROUND: The aim of study was to evaluate outcome of international treatment protocol LCH II for children with Langerhans cell histiocytosis treated in FN Motol. METHODS AND RESULTS: Between November 1995 and December 2003, 46 children were treated, sex ratio M:F 29:17 and median age at diagnosis 6 years 8 months. 28 children (60.9%) suffered from monosystem disease with majority of bone lesions (23 times) with skull predominance (16 times). Surgery was primary treatment modality for monosystem disease. Five children with recurrence were successfully treated by protocol LCH II - LR (3x) and LCH III - LR /G2/, respectively. Eighteen children (39.1%) suffered from multisystem disease. 6 out of 18 patients were treated according to low-risk protocol LCH II - LR and 12 children by high-risk scheme LCH II - HR at the non-randomized branch included etoposide. Recurrence was revealed in 11 patients and 10 of them reached 2nd or 3rd complete remission (CR) by 2 - chlorodeoxyadenosine (CDA) monotherapy, and 1 child reached 2nd CR by LCH II - HR scheme. Two children underwent irradiation after bone lesion excision as well as 1 child as supplemental treatment. Totally, 29 children (63.0%) achieved 1st CR, 14 (30.4%) 2nd CR, 2 (4.4%) 3rd CR, and 1 child died because of LCH progression. There were no severe side effects of chemotherapy. Follow-up median time was 5 years 8 months (range 9 months - 9 years 6 months). CONCLUSIONS: LCH II protocol is safe and effective. Results revealed that treatment of patients with multisystem disease might demand some treatment modification.

Adolescent↗

Acute toxicity of binary mixture benzene-ethanol and partition coefficient K(ow) of benzene and ethanol.

The study related to partition coefficients between n-octanol and water of compounds in binary mixture benzene-ethanol was carried out. Partition coefficients of benzene and ethanol for different values of molar ratio of benzene in the mixture were determined. Collected results show statistically significant deviations the K(ow) of benzene for some molar ratios (0.2 to 0.6) from values for pure compound. For ethanol, there are no statistically significant deviations from values for pure compound, however there are some trends of changes of K(ow).

Animals↗

Distribution of the extracellular matrix glycoproteins in ependymomas--an immunohistochemical study with follow-up analysis.

The extracellular matrix (ECM) plays a critical role in influencing the biological behavior of brain tumors and the diagnostic detection of ECM components in ependymomas might be of prognostic value. In the present study we evaluated immunohistochemically the expression of a spectrum of ECM glycoproteins (tenascin, vitronectin, fibronectin, laminin, collagen types II, IV and VI) in a series of 36 pediatric intracranial ependymomas. The distribution of the ECM glycoproteins was evaluated both within the tumor tissue and at the tumor invasion front, and the prognostic value of the results was tested in a survival analysis. The expression of most of the ECM glycoproteins was associated only with blood vessels. Tenascin and vitronectin were found in a more diffuse pattern around the tumor cells and at the tumor invasion fronts of several cases. The progression-free survival was significantly decreased for patients with tenascin positive tumors (in any of the studied compartments) and for the tumors with vitronectin accumulation at their invasion fronts. In one ependymoma containing foci of cartilage with metaplastic ossification we demonstrated that collagen types II and VI and tenascin were present in ECM of both the cartilage and the ependymoma, and were accompanied by areas of necrosis and dystrophic calcifications. We suggest, that the rare simultaneous production of the specific ECM components might lead to the formation of chondroid areas in ependymomas. An abundant production of some ECM glycoproteins (tenascin and vitronectin) is present in a proportion of ependymomas and its immunohistochemical detection is of prognostic relevance.

Adolescent↗

[Monoclonal gammopathies in a series of 1683 plasma donors].

BACKGROUND: Monoclonal gammopathies are very heterogenic groups of disorders characterized by the proliferation of a single clone of plasma cells producing a monoclonal immunoglobulin (paraprotein). Monoclonal gammopathies (Kyle) are classified as malignant monoclonal gammopathies and monoclonal gammopathy of the undetermined significance. The prevalence of paraproteinemias is about 1% in people up to the age of 60 and about 10% in persons older than 80 years of age. METHODS AND RESULTS: We examined blood serum from 1683 plasma donors (18-60 years) by electrophoretic analysis during the period 1999-2003. We determined monoclonal immunoglobulins in 10 of them (0.6%). The presence of monoclonal gammopathies of undetermined significance was the most frequent (6x), one case was a transient monoclonal gammopathy, two patients were not examined and one patient (46 years old man) had the diagnosis of multiple myeloma. The immunoglobulin class of six paraproteins IgG were observed (4x kappa, 2x lambda), paraprotein IgA was found in two patients (1x kappa, 1x lambda), paraproteinemia IgM-kappa in one patient and double paraproteinemia IgG-kappa + IgA-kappa was proved in another one. M-gradient was determined in nine cases by screening electrophoretic analysis on the agarose gel (SEBIA, France). One M-protein (IgA-lambda) was hidden in beta-globulin region and the diagnosis of multiple myeloma was determined after clinical manifestation this disease. CONCLUSIONS: Our study shows, that electrophoretic analysis of serum is necessary to do in all types of blood donors (plasma, blood, thrombocytes). Reliable proof of monoclonal immunoglobulins in blood serum or urine is given only by immunofixation electrophoresis.

Adolescent↗

[Suprasegmental effects of selective posterior rhizotomy].

The occurrence of spasticity is most commonly attributed to the lack of presynaptic inhibition. Perinatal damage to the central nervous system, as it happens in cerebral palsy, leads to pathological reflex response both on segmental and polysegmental levels. It results not only in clinical signs typical for spasticity but also in alterations of brainstem function, such as dysarthria or congenital nystagmus. Selective posterior rhizotomy is a neurosurgical method, routinely used in the treatment of spasticity. The lumbosacral posterior roots are partially cut under perioperative neurophysiological control. The aim of the treatment is the reduction of afferentation for posterior horns resulting in a decrease of pathological reflex responses. Selective posterior rhizotomy consequently decreases lower limbs spasticity. The improvement of upper extremities fine skills, the improvement of speech and cognitive functions has been also observed after selective posterior rhizotomy. The possible pathophysiological explanations of these so-called suprasegmental effects are discussed in the article.

Cerebral Palsy↗

[Fibrillary glomerulonephritis--a rare cause of nephrotic syndrome].

Fibrillary glomerulonephritis (FGN) is a rarely diagnosed disease with clinical manifestations such as proteinuria, microscopic hematuria, nephrotic syndrome or decreased kidney function. Around one half of patients develop chronic renal failure in the course of several years. The diagnosis of fibrillary glomerulonephritis is to be established only basing on the results of renal biopsy. Pathognomonic is the electron-microscopic examination, evidencing fibrillar deposits in mesangium and in basal membranes of glomeruli. Fibrils are similar to those seen at amyloidosis, however, with larger diameter, non-linear deposition and do not stain with Congo red or thioflavin T. Immunofluorescency test usually shows the presence of IgG, namely the subclasses IgG4, C3 and kappa and lambda of light immunoglobulin chains. The presented case report describes clinical and laboratory findings at a patient suffering from nephrotic syndrome. Results of renal biopsy and detailed histological examinations concluded the diagnosis as fibrillary glomerulonephritis. The patient was treated with a combination of prednisone (1 mg/kg/24 hrs) with cyclophosphamide (2 mg/kg/24 hrs) for six months. This led to a decrease of proteinuria from the initial value of 5.38 g/24 hours to 1.88 g/24 hours, as well as to a partial remission of nephritic syndrome. Glomerular filtration, evaluated using endogenous creatinine clearance, remained within limits of normal values throughout the follow-up, with the value of 2.6 ml/s after the treatment.

Glomerulonephritis↗

A rapid HPLC method for the determination of carboxylic acids in human urine using a monolithic column.

A rapid HPLC method for the determination of carboxylic acids in urine samples using a Chromolith Performance RP/18e 100/4.6 with Chromolith Guard Cartridge RP/18e 10/4.6 (Merck KgaA, Darmstadt, Germany) was developed. The method facilitates the simultaneous determination of aromatic hydrocarbon metabolites mandelic acid (MA) and phenylglyoxylic acid (PGA) from styrene and ethylbenzene, hippuric acid (HA) from toluene and 2-, 3-, 4-methylhippuric acids (MHA) from xylene. 3-hydroxybenzoic acid (3-HBA) was used as internal standard. A chromatographic run is completed within less than 5 min for styrene, ethylbenzene and toluene metabolites, and within 10 min for xylene metabolites. The detection limits are 9 mg L(-1) urine for MA, 1.25 mg L(-1) urine for PGA, 4.9 mg L(-1) urine for HA, 22 mg L(-1) urine for 2-MHA, and 18.5 mg L(-1) urine for 3-MHA. No significant differences of the MA, PGA and HA concentrations in human urine samples obtained by HPLC chromatography on LiChrosorb RP 18 and on Chromolith RP/18e columns were found. The results were evaluated by using ANOVA.

Calibration↗

Human urine certified reference material CZ 6009: creatinine, styrene metabolites (mandelic acid and phenylglyoxylic acid).

The reference material was prepared by freeze-drying pooled urine samples obtained from healthy persons occupationally exposed to styrene. The concentrations of mandelic acid (MA), phenylglyoxylic acid (PGA), and hippuric acid (HA) in urine were determined by three modes of high-performance liquid chromatography (HPLC). For isochronous stability testing the urinary mandelic acid and phenylglyoxylic acid concentrations were followed over a 24-month period for a preliminary batch by use of HPLC. No changes of the concentration values were found. The creatinine concentration was stable for more than five years. Standard Reference Material NIST 914a Creatinine was used for traceability purposes for creatinine. Pure chemicals MA and PGA were used for traceability purposes. Control material ClinChek-Urine Control (Recipe) was analyzed simultaneously. The mean values of MA and PGA compare well with the means and fall within the control range of control samples. Results from homogeneity, stability, and traceability testing were evaluated using the statistical program ANOVA. The certified values and their uncertainties were evaluated from the results of interlaboratory comparisons, and homogeneity and stability tests. The values are unweighed arithmetical averages of accepted results and their uncertainties are combined uncertainties (coverage factor=1).

Adult↗

Synechocystis 6803 mutants expressing distinct forms of the Photosystem II D1 protein from Synechococcus 7942: relationship between the psbA coding region and sensitivity to visible and UV-B radiation.

Synechocystis PCC 6803 mutants expressing either the "low light" (D1:1) or the "high light" (D1:2) form of the Photosystem II (PSII) D1 protein from Synechococcus PCC 7942 were constructed and characterized with respect to properties of PSII and sensitivity to visible and UV-B radiation. The AI and AIII mutants (containing only the D1:1 and D1:2 forms, respectively) exhibited very similar PSII characteristics as the control strain and they differed only in the accelerated decay kinetics of flash-induced variable fluorescence measured in the presence of DCMU. However, the mutants showed increased sensitivity to photodamage induced by visible and UV-B radiation, with higher loss of PSII activity in the AI than in the AIII strain. Thus, the difference between strains containing D1:1 and D1:2 found previously in Synechococcus 7942 is maintained after transfer of corresponding psbA genes into Synechocystis 6803 and is directly related to the coding region of these genes. The higher light sensitivity of the AI mutant is caused partly by the higher rate of photodamage and partly by the less efficient PSII repair.

Cyanobacteria↗

Two-dimensional nonlocal model of axially and radially inhomogeneous plasma of cylindrical magnetron discharge.

A cylindrical magnetron discharge (CMD) with two coaxial electrodes, a uniform axially directed magnetic field, and discharge ends closed by the shields biased at the cathode potential is considered. The presence of the shields creates axial inhomogeneity of plasma, which is taken into account in this study. At low pressures and small magnetic fields the pronounced nonlocal regime of the electron distribution function (EDF) formation is realized. The electron component is analyzed on the basis of radially and axially inhomogeneous Boltzmann kinetic equation. Unmagnetized electrons that move in axial direction are trapped in the axial potential well, their energy relaxation length exceeds the discharge vessel length, and the kinetic equation can be averaged over axial flights of electrons. Using a model two-dimensional potential profile, the EDFs at the different axial positions are obtained and two-dimensional distributions of the electron density, ionization rate, and current on cathode are calculated. The results of the modeling and experiments are compared for the dc CMD in Ar at a pressure of 3 Pa, magnetic field strength of 10 mT, and current of 150 mA.

Journal Article↗

[Histologic findings in protocol biopsies of transplanted kidneys].

Fourty eight patients with cadaveric kidney allografts treated by cyclosporin A (CSA) or tacrolimus (FK506) underwent protocol graft biopsies at 1, 3 and 12 months after transplantation, and 110 biopsy specimens were obtained. Histologic diagnosis was made according to the Banff scheme. The main cause of the graft instability at 1 and 3 months was acute clinical rejection, these biopsies showed all known histological patterns of tubulointersticial and vascular rejection. Acute tubular nephropathy was found in 13% and borderline changes or nephrotoxicity in 8.7% of instable grafts. Specifically, we focused on the occurRence of subclinical rejection and toxic reactions in stable renal allografts. Of these, 36.1% showed histological patterns of acute tubulointersticial and vascular rejection. The Banff score of subclinical rejection was significantly lower than in clinically apparent rejection. CSA and tacrolimus nephrotoxicity were seen in 14.2%, 19.5% and 27.2% of specimens at 1, 3 and 12 months, respectively. In over one half of the identified cases of nephrotoxicity neither increased level of immunosuppression nor features of allograft dysfunction were found. At 12 months, 45.5% of specimens showed mild chronic transplant nephropathy and 18.1% moderate chronic transplant nephropathy. Normal morphology was found in 36.4% of biopsies. We found a high prevalence of subclinical rejection and nephrotoxicity in the studied cohort. We conclude that protocol biopsy is a reliable method in the diagnosis of clinically silent, as well as clinically apparent, disorders of the transplanted kidney.

Biopsy, Needle↗