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Biomedical subjects

J Malý

Publications and source records attributed to J Malý.

At least 19 recordsLinked to original sources

Tolerance to acute ischemia in adult male and female spontaneously hypertensive rats.

Clinical and experimental studies have repeatedly indicated that overloaded hearts have a higher vulnerability to ischemia/reperfusion injury. The aim of the present study was to answer the question whether the degree of tolerance to oxygen deprivation in hearts of spontaneously hypertensive rats (SHR) may be sex-dependent. For this purpose, adult SHR and their normotensive control Wistar Kyoto (WKY) rats were used. The isolated hearts were perfused according to Langendorff at constant pressure (proportionally adjusted to the blood pressure in vivo). Recovery of contractile parameters (left ventricular systolic, diastolic and developed pressure as well as the peak rate of developed pressure) was measured during reperfusion after 20 min of global no-flow ischemia in 5 min intervals. Mean arterial blood pressure was measured by direct puncture of carotid artery under light ether anesthesia in a separate group of animals. The degree of hypertension was comparable in both sexes of SHR. The recovery of contractile functions in SHR males and females was significantly lower than in WKY rats during the whole investigated period. There was no sex difference in the recovery of WKY animals; on the other hand, the recovery was significantly better in SHR females than in SHR males. It may be concluded that the hearts of female SHR are more resistant to ischemia/reperfusion injury as compared with male SHR. This fact could have important clinical implications for the treatment of cardiovascular disease in women.

Animals↗

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↗

["Unknown" cause of the onset and recurrence of venous thromboembolism].

We reported the case of 61 years old man with the first episode of massive pulmonary embolism at the age of 54 without the proper explanation of the cause. Thrombocythaemia was manifested after the dismissal from the hospital but the origin of this condition was not clarified. Essential thrombocythaemia was diagnosed after the recurrence of venous thromboembolism and that is the explanation for thrombophilic condition in this patient. The patient is without problems and signs of recurrent venous thromboembolism after the achievement of the complete remission of myeloproliferative disease and well-managed of anticoagulation therapy.

Humans↗

[Prevention of venous thromboembolism in internal medicine and neurology].

Many hospitalized patients are under an increased risk of venous thromboembolism. They should have adequate pharmacological prophylaxis. Clinical studies including meta-analyses prove that low molecular weight heparin prophylaxis of venous thromboembolisms is equally effective as that employing unfractionated heparin and it features less bleeding complications. The effectiveness of pharmacological prophylaxis with low molecular weight heparin in hospitalized patients at internal medicine departments has been proven by the MEDENOX study when enoxaparin in a dose of 40 mg was administered subcutaneously and the PREVENT study when subcutaneous dalteparin 5 000 units j. was administered daily. In the MEDENOX study, enoxaparin administration was confirmed to decrease the relative risk of venous thromboembolisms by 63% without increasing any adverse effects during the prophylaxis and the PREVENT study showed that dalteparin administration was followed by a highly significant reduction of asymptomatic venous thromboses in hospitalized patients. According the ACCP guideline for thromboprophylaxis in hospitalized internal medicine patients with clinical risk factor of venous thromboembolism (tumors, heart failures, sepsis, VTE history and serious pulmonary condition), low molecular weight heparin or mini-doses of unfractionated heparin are to be administered. The recent recommendations discourage the use of acetyl-salicylic acid in monotherapy treatment for venous thromboembolism prevention.

Anticoagulants↗

[Mean platelet volume (MPV) in Crohn's disease patients].

BACKGROUND: Platelets are involved in the pathogenesis of chronic inflammation. Thrombocyte count and platelet volume are considered as a useful activity marker of inflammatory bowel disease. The aim of the study was to compare the yield of mean platelet volume with clinical and other laboratory markers of activity in Crohn's disease (CD). METHODS AND RESULTS: A total of 56 patients with CD were investigated at time of evident clinical relapse and remission (29 males and 27 females, aged 19-68 years, mean 34.5, median 31.5 years). Complete blood count, C- reactive proteins were measured. Disease activity was assed by the Crohn's Disease Activity Index (CDAI). Patients were checked at least twice (120 analyses were carried out in total). Thrombocytosis (above 350xl09/L) was found in 32/61 (52 %) patients with clinical relapse and in 7/59 (12 %) patients with clinical remission (mean 400.7x10(9)/1; 95%CI: 361.1-440.3x10(9)/1; or as the case may be mean 278.6xl0(9)/1; 95% CI: 256.8-300.4x10(9)/1). The mean platelet volume decreased (under 7.8 fL) in 19/61 (31 %) patients with clinical relapse and in 8/59 (13.5 %) with clinical remission (mean 8.333 fl; 95% CI: 7.935-8.731 fl; or as the case may be mean 9.200 fl; 95% CI: 8.824-9.576 fl). Total platelet count, CDAI and C- reactive protein were significantly increased (p<0.0001) and mean platelet volume was statistically significantly reduced (p=0.003) during clinical relapse compared with clinical remission. CONCLUSIONS: Decreased mean platelet corpuscular volume is an independent laboratory marker of clinical disease activity. However, on the basis of our study, its predictive value is inferior compared to the total platelet count, serum concentration of C- reactive protein and Crohn's disease activity index.

Adult↗

Degradation and movement in soil of the herbicide isoproturon analyzed by a Photosystem II-based biosensor.

We have examined the persistence and movement of a urea-type herbicide, isoproturon [IPU; 3-(4-isopropylphenyl)-1,1'-dimethylurea], in soil using a novel herbicide-detection device, the prototype of a portable electrochemical biosensor based on Photosystem II particles immobilized on printed electrodes, and evaluated its results against two other methods: (i) chlorophyll-fluorescence bioassay based on polyphasic induction curves, and (ii) standard analysis represented by liquid chromatography. The data of the herbicide's content determined in soil extracts from field experiments correlated in all three methods. The biosensor assay was effective in determining the herbicide's concentration to as low as 10(-7) M. The results of our experiments also showed the kinetics of movement, degradation, and persistence of isoproturon in various depths of soil. After 6 to 9 wk, almost half of the isoproturon was still actively present in the upper soil layers (0-10 and 10-20 cm) and only 5 to 10% of biological activity was inhibited in the deeper soil layer tested (20-30 cm). Thus, inhibition within the limit of detection of both bioassays could be observed up to 9 wk after application in all profiles (0-30 cm), whereas inhibition persisted for up to 11 wk in the upper soil profile (0-10 cm). The use of the biosensor demonstrated its possibility for making rapid and cheap phytotoxicity tests. Our biosensor can give preliminary information about the biological activity of isoproturon in hours--much faster than growth biotests that may take several days or more.

Biodegradation, Environmental↗

[Mechanical cardiac support--the first use in Czech Republic].

BACKGROUND: Implantation of mechanical assist device is widely accepted modality of treatment of patients with refractory heart failure. In the present study we evaluated our first one-year experiences with this method for bridging patients to cardiac transplantation. METHODS AND RESULTS: Between April 2003 and May 2004, the Thoratec VAD (Thoratec, Pleasanton, CA, USA) was implanted in 6 patients ( males; age 28-61 years) as a bridge-to-transplant procedure after having received maximum inotropic support and who were at imminent risk of death. In all patients was performed VAD as biventricular device (BiVAD). During a week after placement was observed recovery of organs function in all patients. Five patients survived to heart transplantation. One patient died 21 days after BiVAD placement due to massive bleeding to the respiratory tract. In post-transplantation period 1 patient died second day from acute graft failure and other patient died 34 days after from intracranial bleeding. Three patients has been discharged from the hospital and they are surviving more than I year. CONCLUSIONS: Analysis of our first experiences with the Thoratec BiVAD implantation as bridging to heart transplantation suggests that it is well suited method with respect to long- term prognosis of this group of patients.

Adult↗

[Long-term follow up of renal function after orthotopic liver transplantation].

BACKGROUND: Renal dysfunction in patients after the orthotopic liver transplantation (OLT) is frequent and it significantly contributes to the morbidity and mortality. The aim of our work was to assess the level of glomerular function (GFR) within the first to fifth year after OLT. METHODS AND RESULTS: Serum creatinine concentration (Skr), creatinine clearance (Ckr) and predicted value of creatinine clearance using the Cockcrofta a Gaulta formula (CG) were assessed in 75 patients. Normal values of the given parameters (Skr <110 umol/l, Ckr > or = 1.3 ml/s/1.73 m2) were found only in 16% of all patients. Significant decrease of GFR (Ckr < 0.5 ml/s/1.73 m2) was found in 24% of cases, acute renal failure, which required transitory haemodialysis developed in 4% of patients. In 60% of patients various degree of GFR decrease was found without the necessity of haemodialysis. CONCLUSIONS: Level of renal functions was not significantly related to the blood pressure or serum lipids concentration. An important factor appeared to be the level of renal function before OLT. Because the level of renal function after OLT can significantly influence the post transplantation development, regular follow up of GFR is recommended.

Adolescent↗

[The frequency of venous thromboembolism in women with Leiden mutation in association with pregnancy and puerperium].

OBJECTIVE: The assessment of the frequency of venous thromboembolism (VTE) in women with F V Leiden in association with pregnancy and puerperium and according these results and available data to formulate the principles of thromboprophylaxis. TYPE OF STUDY: Retrospective case control study. MATERIALS AND METHODS: The assessment of frequency of VTE in the group of 224 women with F V Leiden in heterozygous form in association with 460 pregnancies and in the group of 40 women with F V Leiden in homozygous form in association with 70 pregnancies. This frequency of VTE in those groups was compared with the frequency of VTE in the control group of 201 women without F V Leiden in association with 422 pregnancies. F V Leiden evaluation was done in the period of 1996-2003. RESULTS: In the group of women with F V Leiden in heterozygous form VTE occurred 44-fold during pregnancy and puerperium. In 17 cases VTE was manifested in pregnancy (once in Ist trimester, twice in IInd trimester, 14 times in IIIrd trimester), in 27 women VTE occurred in puerperium and always within the first 10 days after delivery. Proximal venous thrombosis was diagnosed in 34 cases, in 5 cases being complicated by pulmonary embolism. In 10 women thrombosis was distal. The frequency of VTE is 9.6%. In the group of women with homozyous form VTE occurred in 14 cases (20%). In 5 cases VTE occurred during pregnancy, in 9 cases after delivery and in all cases within first 2 weeks after delivery. The frequency of VTE in the control group is 0.24%. The results were statistically assessed by Fishers exact test in programme NCSS 2004. Frequency of VTE in both cohorts of women with F V Leiden reached statistical significance in comparison with the control group. CONCLUSION: Pregnancy and puerperium are significant risk factors for VTE in the group of women with F V Leiden in heterozygous form and mainly in homozygous form.

Factor V↗

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↗

[Acetylsalicylic acid (ASA) resistance in patients with ischemic heart disease (IHD) as bioindicator of the treatment strategy].

BACKGROUND: The interest in aspirin resistance has been increasing during the last few years, with researchers earnestly pursuing alternative anti-platelet therapies and devices for measuring platelet aggregation. The recent studies suggest that 5-45% of patients taking aspirin do not experience adequate anti-platelet effects. METHODS AND RESULTS: There is scant evidence proving that aspirin resistance has some clinical consequences. To assess the prevalence of aspirin resistance in patients with ischemic heart disease (IHD) two independent methods were used: platelet aggregation in platelet rich plasma (PRP) after induction by propylgallate (CPG), and assessment of platelet function by PFA 100 method. The study population consisted of 424 patients treated for IHD on the 2nd Dept. of Medicine, Teaching Hospital, Hradec Kralove. The age, gender, diagnosis and effect of therapy were characterized in this group of the patients. Daily ASA dose was 100 mg. We used two methods to monitor ASA treatment efficacy: a) thrombocyte aggregation after induction by CPG, b) the assessment of platelet function by PFA 100 method. a) Of the patients studied by CPG platelet aggregation, 51 (12.1%) pts were resistant to ASA dose 100 mg/day, and 32 (7.6%) pts remained resistant even after increasig the dose to 200 mg/day. In 80 (20%) pts, the daily ASA dose of less than 100 mg was sufficient to inhibit platelet function. b) Although the PFA-100 system is not able to detect the difference between low and high ASA dose, we found 53 (15.2%) patients aspirin resistant using this method. CONCLUSIONS: In the patients with IHD treated with 100 mg of ASA per day, our study has shown that the prevalence of aspirin resistance was 12.1% using CPG method, and 15.2% using PFA-100 method. Aspirin resistance was dose dependent. Prevalence of ASA resistance in patients treated with 200 mg of ASA per day was only 7.6% using the CPG method.

Adolescent↗

[Contemporary programme of pharmaceutical studies in Germany].

In the year 2002, both the Czech and Slovak Faculties of Pharmacy celebrated the fiftieth anniversary of the existence of four-year and later five-year university courses of pharmaceutical studies, the contents of which were being continuously modified in order to comply with principal trends in the field of pharmacy. A new programme of pharmaceutical studies which has just started at German universities can serve us as a certain example and provide comparison, or inspiration.

Curriculum↗

Selectins and monocyte chemotactic peptide as the markers of atherosclerosis activity.

The role of adhesive selectin molecules in the process of atherogenesis is an open question. These molecules are known as markers of atherosclerosis activity, however, only some biological mechanisms are known up to now. In this study we examined the levels of soluble forms of E-, P-selectin and monocyte chemotactic protein (MCP-1) in the process of extracorporeal cholesterol elimination by LDL-apheresis. We measured the levels of sE-, sP-selectin and MCP-1 in the plasma before and after LDL-apheresis and in the washout solution from immunoabsorption columns Lipopak. Eighty measurements were performed repeatedly in 6 patients with severe familial hypercholesterolemia (FH) on long-term LDL-apheresis treatment. Before the procedure P-selectin levels were 204+/-179 ng/ml, E-selectin 32.1+/-33.7 ng/ml, MCP-1 323.8+/-121 pg/l, whereas after the procedure we found P-selectin levels 131.6+/-34 ng/ml, E-selectin 33.1+/-51 ng/ml, and MCP-1 200.4+/-15 pg/l. Levels of P-selectin were increased in the blood of patients with FH in spite of long-term intensive extracorporeal LDL-elimination, documenting thus the activity of atherosclerosis. The levels of P-selectin and MCP-1 decreased significantly after the hypolidemic procedure and could be used as another marker showing the effectivity of the extracorporeal LDL-cholesterol elimination (immediately after the procedure), and, after further verification, may serve as a marker for controlling the therapy efficacy.

Arteriosclerosis↗

Chronic endothelin receptor blockade reduces end-organ damage independently of blood pressure effects in salt-loaded heterozygous Ren-2 transgenic rats.

The present study was performed to evaluate the role of an interaction between the endothelin (ET) and the renin-angiotensin systems (RAS) in the development and maintenance of hypertension and in hypertension-associated end-organ damage in heterozygous male and female transgenic rats harboring the mouse Ren-2 renin gene (TGR). Twenty-eight days old heterozygous TGR and age-matched transgene-negative normotensive Hannover Sprague-Dawley rats (HanSD) were randomly assigned to groups with normal-salt (NS) or high-salt (HS) intake. Nonselective ET(A)/ET(B) receptor blockade was achieved with bosentan (100 mg.kg(-1).day(-1)). All male and female HanSD as well as heterozygous TGR on NS exhibited 100 % survival rate until 180 days of age (end of experiment). HS diet in heterozygous TGR induced a transition from benign to malignant phase hypertension. The survival rates in male and in female heterozygous TGR on the HS diet were 46 % and 80 %, respectively, and were significantly improved by administration of bosentan to 76 % and 97 %, respectively. Treatment with bosentan did not influence either the course of hypertension (measured by plethysmography in conscious animals) or the final levels of blood pressure (measured by a direct method in anesthetized rats) in any of the experimental groups of HanSD or TGR. Administration of bosentan in heterozygous TGR fed the HS diet markedly reduced proteinuria, glomerulosclerosis and attenuated the development of cardiac hypertrophy compared with untreated TGR. Our data show that the ET receptor blockade markedly improves the survival rate and ameliorates end-organ damage in heterozygous TGR exposed to HS diet. These findings indicate that the interaction between the RAS and ET systems plays an important role in the development of hypertension-associated end-organ damage in TGR exposed to salt-loading.

Administration, Oral↗

[The activation of haemostasis during radiofrequency catheter ablation].

The aim of the study was to investigate chosen haemostasis activation markers during electrophysiologic study (EPS) with consequent radiofrequency catheter ablation (RFA). Sixty-three patients were studied prospectively. Indications for EPS and RFA were supraventricular tachycardias with the arrhythmogenic substrate located in the right atrium. Blood samples were drawn 24 hours before the procedure (T -1), at the beginning of the procedure (T0), at the end of EPS (T1), 30 minutes after completion of RFA (T2), and 24 hours after the procedure (T3). To study coagulation, fibrinolytic and platelet activation were measured concentrations of thrombin-antithrombin III (TAT), D-dimers (DD), platelet count and parameters, and circulating platelet aggregates (CPAi). During the EPS and RFA, TAT levels increased from the baseline 5.03 +/- 2.53 microg/l (T -1) to 12.90 +/- 12.83 microg/l at T0 (p < 0.001) to 36.07 +/- 15.59 microg/l at T1 (p < 0.001) and decreased to 28.85 +/- 13.14 microg/l at T2 (p < 0.001). Levels of DD increased from 0.30 +/- 0.20 mg/l at T0 to 0.44 +/- 0.25 mg/l at T1 (p < 0.001) and to 0.87 +/- 0.74 mg/l at T2 (p < 0.001). The number of platelets was significantly decreased (-13.7%) before and during the procedure (T -1 vs. T3; p < 0.001). Marked platelet activation (CPAi 0.62 +/- 0.32) was observed before the procedure opposite to the physiological values (CPAi 1.0 +/- 0.1), without changes during the procedure (CPAi at T2 0.69 +/- 0.23). Our results confirmed activation of several haemostasis parameters during EPS and RFA, and support eligibility of the antithrombotic prevention in patients indicated for EPS and RFA.

Adult↗

Potential risk of infection transmission during storage and transplantation of hematological progenitor cells. Safety assurance.

In a group of 71 patients and 22 donors the danger of infection transmission by infusion of cryopreserved peripheral blood progenitor cells to the patient and/or cross contamination of stored grafts was evaluated. No laboratory signs of active infection were found in 15 donors (13 related, 2 unrelated; 68%) and in 55 patients (77%). Active infection by herpesviruses was the most common (in 13 patients and 7 donors), hepatitis B being found in only one case. The cytomegalovirus IgG test was the most common marker of previous infection; it was found in 14 donors and 55 patients. The rate of clinically unsuspected infections in donors and patients including cases requiring immediate treatment among the patients group is relatively high and fully justifies the practice of prophylactic serological testing in the whole range of tests according to the European Blood and Marrow Transplantation Group and International Society for Hematotherapy and Graft Engineering in both autologous and allogeneic transplantations of hematopoietic stem cells.

Bone Marrow Transplantation↗

[Tubular function after orthotopic liver transplantation].

Renal function after orthotopic liver transplantation (OTL) is very frequently reduced and its level exerts a significant effect on the morbidity and mortality of these subjects. One of the main factors with a negative impact on renal function after OTL is the nephrotoxic action of cyclosporin A (CsA). Renal function after OTL is usually evaluated on the basis of glomerular filtration (GF). As chronic nephrotoxicity of CsA is manifested in the histological picture by significant tubulointerstitial affection, in 75 subjects after OTL the spontaneous concentrating and acidifying capacity of the kidneys was investigated. The value of urine osmolality (UOSM) assessed after noctunal withdrawal of fluids was in 72.7% lower than in healthy subjects and did not reach 600 mOsm/kg H2O, although the serum creatinine concentration (Scr) was still within the normal range. The pH value of the morning urine did not reach in 38.2% the required value of 6.0 although Scr was within the normal range. Between values of UOSM after nocturnal liquid withdrawal and GF assessed on the basis of inulin clearance (Cin) was a significant direct relationship, however the scatter of values was considerable (r = 0.226, p < 0.05). Between pH values of the morning urine and Cin no correlation was found. The assembled results support the idea that the concentrating activity of the kidneys in subjects after OTL treated with CsA is reduced. This reduced concentrating capacity is already apparent on the basis of UOSM of morning urine after nocturnal fluid withdrawal. Although this defect is also frequent in subjects with a normal Scr value, the authors assume that the use of this simple evaluation of the concentrating capacity (it does not burden the patient nor the attending staff) could be useful in the early diagnosis of tubulointerstitial affection.

Adolescent↗