A novel concept for dynamic adjustment of auditory space.

Traditionally, the auditory system is thought to serve reliable sound localization. Stimulus-history driven feedback circuits in the early binaural pathway, however, contradict this canonical concept and raise questions about their functional significance. Here we show that stimulus-history dependent changes in absolute space perception are poorly captured by the traditional labeled-line and hemispheric-difference models of auditory space coding. We therefore developed a new decoding model incorporating recent electrophysiological findings in which sound location is initially computed in both brain hemispheres independently and combined to yield a hemispherically balanced code. This model closely captures the observed absolute localization errors caused by stimulus history, and furthermore predicts a selective dilation and compression of perceptional space. These model predictions are confirmed by improvement and degradation of spatial resolution in human listeners. Thus, dynamic perception of auditory space facilitates focal sound source segregation at the expense of absolute sound localization, questioning existing concepts of spatial hearing.

The purple toe syndrome in female with Factor V Leiden mutation successfully treated with enoxaparin.

Purple toe syndrome is a rare complication of warfarin therapy. It occurs usually after 3 to 8 weeks of therapy and it is caused by cholesterol emboli from atheromatous plaque. Sudden onset of pain in affected area, typically in toes and feet, is the main characteristic of the syndrome. We describe a case of a 65-year-old female with purple toe syndrome after 6 weeks of warfarin. Indication of warfarin was a proximal deep venous thrombosis, which developed after prolonged immobilization. Factor V (FV) Leiden and persistent high FVIII activity were found as additional eliciting factors for venous thromboembolism. After warfarin withdrawal and enoxaparin treatment, symptoms disappeared promptly but a slight discoloration of the toe persists.

[New antithrombotics in the prevention of venous thromboembolia and new anti-platelet drugs]. / Nová antitrombotika v prevenci zilní tromboembolie a nové protidestickové léky.

We first present a brief overview of new antithrombotic agents that are assumed to replace coumarines and heparin in many indications; this overview provides information on pentasaccharides, direct thrombin inhibitors and direct factorXa inhibitors. Secondly, since the new drugs with antiplatelet effect act through blockade of the reactions involved in blood platelet activation, we review and discuss the substances that interfere with this process. The current antiplatelet therapy focuses mainly on an inhibition of platelet aggregation stimulated by ADP, reducing the risk of arterial occlusions.

Hemostatic changes before and during electrophysiologic study and radiofrequency catheter ablation.

We sought to investigate specific hemostasis activation markers during electrophysiologic study (EPS) with consequent radiofrequency catheter ablation (RFA). Sixty patients were studied prospectively during routine EPS with RFA for paroxysmal supraventricular tachycardia. Blood samples were drawn before the insertion of venous sheaths (T0), at the end of EPS (T1), and 30 min after completion of RFA (T2). To study coagulation and fibrinolytic and platelet activity, we measured concentrations of thrombin-antithrombin III (TAT), D-dimers (DD), plasminogen activator inhibitor type 1 (PAI-1), tissue-type plasminogen activator (t-PA), and circulating platelet aggregates. The results are expressed as median and show 95% confidence levels. Levels of DD increased from 0.24 mg/L at T0 to 0.37 mg/L at T1 (P < 0.001) and to 0.59 mg/L at T2 (P < 0.001). TAT levels increased from 5.29 µg/L at T0 to 35.80 µg/L at T1 (P < 0.001) and decreased to 26.30 µg/L at T2 (P < 0.001). PAI-1 concentration decreased from 30.10 µg/L at T0 to 26.4 µg/L at T1 (P < 0.001). t-PA at T2 increased to 5.10 µg/L from 4.75 µg/L at T1 (P = 0.001). No other differences between corresponding medians were statistically significant (P > 0.05). We found that concentrations of DD at T2 versus T1 depended on the number of radiofrequency energy applications (r (S) = 0.387; P = 0.002). Marked platelet activation was observed from the start of the procedure, without changes during the procedure.

Angiopoietin-2 mRNA expression is increased in chronic lymphocytic leukemia patients with poor prognostic features.

Several studies have demonstrated the potential prognostic importance of angiogenesis in chronic lymphocytic leukemia (CLL). Elevated expression of angiopoietin-2 (Ang-2), an angiogenic cytokine, was recently reported in CLL. However, data regarding prognostic significance of Ang-2 in CLL are limited. Therefore, we quantitated Ang-2 mRNA in purified mononuclear cells of 33 untreated CLL patients and compared the transcript levels to traditional as well as modern prognostic factors in patients with CLL (clinical stage, disease course, IgVH mutation status, CD38, and ZAP-70 expression). Elevated Ang-2 mRNA concentrations were detected in 12 cases; 21 patients had very low or undetectable levels of Ang-2 transcript. There was significant association between high Ang-2 mRNA levels and unmutated IgVH genes (n=27, P=0.010) and with CD38 expression (n=32, P=0.011), but not with ZAP-70 expression (n=32, P=0.784), Rai stage (n=33, P=0.305) or stable versus progressive clinical course (n=33, P=0.443). There was a trend towards shorter progression-free survival in patients with high Ang-2 expression; however, it did not reach statistical significance (P=0.090). Our pilot data show that Ang-2 mRNA is differentially expressed in patients with CLL and its increased expression appears to be associated with poor prognostic features. Further studies are needed to confirm the results in a larger patient cohort.

[Blood platelets metabolic and activation processes and options for their inhibition]. / Metabolické a aktivacní deje v krevních destickách a moznosti jejich inhibice.

A range of activation processes and confirmatory and metabolic changes take place in blood platelets following their activation. The paper discusses some of the blood platelet activation steps and describes the specific processes that take place on this level. Furthermore, the points at which it is possible to actively interfere with the blood platelet metabolism or activation processes are described. Antiplatelet treatment focuses on these points and there are efforts to identify active substances that either inhibit access to certain receptors or targets or, alternatively, inhibit the enzymes participating in these processes.

Time-course of tissue factor plasma level in patients with acute coronary syndrome.

Enhanced expression of tissue factor (TF) may result in thrombosis contributing to acute clinical consequences of coronary artery disease. Several studies demonstrated elevated plasma levels of TF in patients with acute coronary syndrome (ACS). The aim of our study was to compare the concentrations of TF in coronary sinus (CS), proximal part of the left coronary artery (LCA) and peripheral vein (PV) of patients with ACS and stable coronary artery disease (SCAD). Time course of the TF plasma levels in PV was followed on day 1 and day 7 after index event of ACS presentation and was compared to day 0 values. No heparin was given prior to the blood sampling. Twenty-nine patients in the ACS group (age 63.6+/-10.8 years, 20 males, 9 females) and 24 patients with SCAD (age 62.3+/-8.1 years, 21 males, 3 females) were examined. TF plasma level was significantly higher in patients with ACS than in those with SCAD (239.0+/-99.3 ng/ml vs. 164.3+/-114.2 ng/ml; p=0.016). There was no difference in TF plasma levels in PV, CS and LCA (239.0+/-99.3 ng/ml vs. 253.7+/-131.5 ng/ml vs. 250.6+/-116.4 ng/ml, respectively). TF plasma levels tended to decrease only non-significantly on the day 7 (224.4+/-109.8 ng/ml). Significant linear correlation between TF and high sensitivity CRP (hs-CRP) levels on day 0 was found. In conclusion, TF plasma levels are elevated in patients with ACS not only locally in CS but also in systematic circulation. Our data support the relationship between TF production and proinflammatory mediators.

[Haemocoagulation and renal insufficiency, haemocoagulation and type 2 diabetes mellitus]. / Hemokoagulace a renálni insuficience, hemokoagulace a diabetes mellitus 2. typu.

Diabetes mellitus is a frequent cause of renal insufficiency. Renal insufficiency is associated with both haemorrhagic manifestations primarily caused by platelet functional disorders, and states of hypercoagulation resulting from significant hyperfibrinogenemia. Fibrinolysis is either increased or, often, decreased. Changes in haemostasis in renal insufficiency have been dealt with by many authors in relevant literature. However, the final stage of renal insufficiency is rather dominated by haemorrhagic diathesis. It is manifested by skin haemorrhage, mucosal manifestations, but also by retroperitoneal and cerebral haemorrhage. The main cause of a haemorrhagic condition is platelet dysfunction combined with anticoagulation and antiplatelet therapy which is used in dialysis. Platelet function disorders are provoked by acquired thrombocytopaenia and result in a disorder in the interaction between the blood vessel wall and the platelet. Dialysis suppresses platelet abnormalities only temporarily by suppressing uremic toxins provoking platelet disorders. On the other hand, dialysis may cause prothrombotic activity. Changes in haemostasis in type 2 diabetes mellitus form part of the insulin resistance syndrome and induce prothrombotic condition due to decreased fibrinolysis.

Primary hemostasis in patients treated with LDL-apheresis for severe familiar hypercholesterolemia: a prospective pilot trial using PFA-100 analysis to rationalize therapeutic LDL-apheresis procedure.

UNLABELLED: LDL-apheresis is a method of extracorporeal elimination of serum LDL-cholesterol used for treating patients with severe hyperlipidemia resistant to diet and pharmacotherapy. A practically applicable marker that may possibly be used to ascertain the efficacy of this treatment in lowering the activity of atherosclerosis are still to be found and remains an unresolved problem. Activity of primary hemostasis plays an important role in the process of developing atherosclerotic complications. This fact led us to hypothesize that the investigation of primary hemostatic activity might be a useful marker for monitoring LDL-apheresis efficacy. The aim of this work was to verify this hypothesis. METHODS AND PATIENTS: Commercial analyzer Dade Behring PFA-100, Germany (PFA, platelet function analysis) was used for all investigations. This analyzer enables quantitative measurement of platelet-mediated hemostasis in uncoagulated (citrated) blood. The method simulates platelet activation by mechanical stress (shear stress), and also simulates contact of platelets with collagen. A total of nine long-term treated patients with familial hypercholesterolemia were included in the study group (4 females and 5 males). Ages ranged from 17 to 59 years (average 46.4, median 55). Two patients had homozygous hypercholesterolemia. Eighteen sample pairs were examined using collagen/epinephrine (COL/EPI) membrane and 17 pairs were examined using collagen/ADP (COL/ADP) membrane, the total number of samples amounted to 70. RESULTS: Closure time (CT) values were prolonged after separation in all cases but CT prolongation was not statistically significant (p < 0.14). No differences between homozygous and heterozygous patients were found (p < 0.05). CONCLUSION: Investigation of primary hemostasis using PFA-100 analyzer is not a suitable marker and should not be used to determine the optimal intensity of individual LDL-apheresis procedures.

The influence of intrinsic coagulation pathway on blood platelets activation by oxidized cellulose.

Oxidized cellulose is an effective hemostat that works naturally to aid in blood coagulation. The mechanism of its action is not very well understood. Little effect on blood coagulation, but a pronounce decrease in platelet count has been reported upon the addition of the oxidized cellulose to the whole blood. As a marker of platelet activation and aggregation we used serotonin release reaction and turbidity changes in time. We found that oxidized cellulose did not activate washed platelets reconstituted in plasma-free medium or plasma-free medium with fibrinogen; no reduction of platelet count was observed. Serotonin release in platelet-rich plasma incubated with oxidized cellulose started in the range from 5 to 10 min. Serotonin release from platelets reconstituted in plasma deficient in either coagulation factor V, VIII, IX, or XII was delayed. Blood platelets activation by oxidized cellulose requires calcium ions present in dispersion of oxidized cellulose. Factor XIII deficiency had no influence on blood platelets activation by oxidized cellulose. Our results clearly indicate the significance of intrinsic coagulation pathway activation on blood platelets activation by oxidized cellulose and so indirectly on the hemostyptic effect of oxidized cellulose.

[Mean platelet volume (MPV) in Crohn's disease patients]. / Strední objem trombocytu u nemocných s Crohnovou chorobou.

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.

[Laboratory monitoring of antithrombotic treatment]. / Laboratorní monitorování antitrombotické lécby.

A number of tests can be employed in monitoring anticoagulant, thrombolytic and antiaggregation treatment. Not all, however, indicate precisely the therapeutic effect of the drug used. Some of them are of linear character and they monitor closely the dosage, others have a series of non-specific reactions and the therapeutic effect is largely influenced by these circumstances. This article describes the individual monitoring systems, it deals with their potential reliability issues, and, also, treatment monitoring issues in various diagnostic environments are discussed.

["Unknown" cause of the onset and recurrence of venous thromboembolism]. / "Nejasná" prícina vzniku a recidivy venózního tromboembolizmu.

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.

[Acetylsalicylic acid (ASA) resistance in patients with ischemic heart disease (IHD) as bioindicator of the treatment strategy]. / Rezistence na kyselinu acetylosalicylovou u nemocných s ischemickou chorobou srdecní jako bioindikátor lécebné strategie.

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.

[The frequency of venous thromboembolism in women with Leiden mutation in association with pregnancy and puerperium]. / Výskyt venózního tromboembolismu u zen s leidenskou mutací v souvislosti s graviditou a sestinedelím.

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.

[The activation of haemostasis during radiofrequency catheter ablation]. / Aktivace hemostázy behem katetrizacní radiofrekvencní ablace.

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.

Hemostyptic effect of oxidized cellulose on blood platelets.

Cellulose is one of the hemostyptic biomaterials, which are able to initiate or accelerate blood coagulation at the site of their application. It belongs to surgical sealants. The mechanism of its action is not clearly understood. We studied the participation of blood platelets in this mechanism. As a marker of platelet activation we used serotonin release reaction. Serotonin release in platelet rich plasma incubated with various concentrations of oxidized cellulose (0.5%-2.0%) started in about 20 min. Washed platelets were not directly activated by oxidized cellulose within one hour. Washed platelets reconstituted in plasma obtained from two patients with coagulation factor XII deficiency were activated by oxidized cellulose with a prolonged lag phase. Our results demonstrate the significant influence of factor XII on blood platelets activation by oxidized cellulose.

[Effect of oxidized cellulose on fibrin formation and blood platelets]. / Vliv oxidované celulózy na tvorbu fibrinu a krevní desticky.

BACKGROUND: Haemostyptic materials initiate and hasten blood clotting at the site of their application. The properties of haemostyptic materials are used for treatment of capillary and parenchymatous haemorrhage along with surgical treatment. Celluloses one of the biopolymers studied for a long time, suitable because of its biocompatibility and non-toxicity. METHODS AND RESULTS: In the submitted study the authors used microdispersed calcium-sodium salt of oxidized cellulose which is formed by oxidation of cellulose in position C6 (patent Alltracel Pharmaceuticals). The authors investigated the effect of oxidized cellulose on fibrin formation and platelets. Using the optic method of the surface plasmon resonance they investigated the initial stage of interaction between fibrinogen and oxidized cellulose. Oxidized cellulose retards and reduces the interaction of the immobilized fibrin monomer with fibrinogen. Fibrin formation was investigated spectrophotometrically at 350 nm. In the presence of cellulose the period of formation of fibrin gel was prolonged and its turbidity increased, depending on the concentration of the cellulose used. The platelet activation by cellulose was assessed by measuring the released serotonin. For the activation of platelets by cellulose the presence of plasma is necessary, rinsed platelets were not activated by cellulose. It was revealed that direct, interaction of rinsed platelets or fibrinogen with cellulose plays a secondary role. CONCLUSIONS: These data and the retarded activation of platelets in plasma with factor XII deficiency indicate that due to negatively charged oxidized cellulose probably activation of the contact coagulation system occurs and this leads to the activation of platelets and fibrin formation.