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N. Kukavica, H. Resić, V. Sahović

Number of hemodialysis patients each day is increasing. The quality of their lives is largely determined by the quality of hemodialysis treatment. One of the most important factors is the type of applied blood approach. The type of blood approach in the most case is artery venous fistula, permanent, temporary catheters, grafts. Any complications of blood strand approach inevitably leads to lower quality of hemodialysis treatment which is connected with not adequate dialysis and poorer general state of patients. Our research was carried out as a prospective study, for the period of 36 months. In the study were included 31 patients, which are on chronic haemodialysis treatment. During this study, we are followed all complications, which occurred at temporary, and permanent tunneled haemodialysis catheters. Complications have occurred in terms of thrombotic problems, low blood flow, occurrence of infection. All patients are divided in two groups, 16 patients with permanent and 15 patients with temporary catheters. In the course of the study was analyzed blood flow and dialysis adequacy (Kt/Vdp) as well as complications and results was compared with randomly selected 16 patients who haemodialysis treatment performed by artery venous fistula (AVF). Two patients were lost to further follow-up to the end of the study. 26 patients at the end of the study had functional catheters, while in the case of 3 patients the catheter was removed. Infection was found in 10 patients while thrombotic complications were observed in 27 cases regardless of catheter type. Mean blood flow in patients with permanent catheter was significantly higher (296,9+/-28,45 cm3/min) compared to patients with temporary catheter (226,3+/-39,8 cm3/min) (p<0,001). Kt/Vdp delivered was 1,22+/-0,15 on patients with permanent catheter and 1,30+/-0,18 for artery venous fistula (AVF) access respectively. The loss of dialysis efficacy using catheters was estimated at 6%. However, in all cases Kt/Vdp values remained above the recommended values (Kt/Vdp > or = 1,2).

UNLABELLED Delayed kidney graft function and acute rejection in the early post-transplant period affect both short and long-term allograft survival. Allograft rejection, as an inflammatory state, results in increased erythropoietin resistance, which leads to decreased haemoglobin (Hb) level. We conducted this study to evaluate whether inflammation in the early post-transplant period could predict later anemia.This is a retrospective cohort study based on the analysis of 64 existing clinical records. PREDICTOR White blood cells (WBC) count obtained by the end of the first week post-transplant (W1). Covariates: Donor's age, recipient's age and sex. OUTCOME Anemia identified at 12 months (M12) post engraftment. Median WBC count at W1 was 9,5 x103/microL (5th - 95th percentile 5,2 x103/microL -17,8 x103/microL). Mean Hb values at M12 were 129,9 +/- 20,3 g/L, in males 136,2 +/- 20,1 g/L and in females 119,4 +/- 16,2 g/L. The significant correlation was found between WBC at W1 and Hb at M12. Pearson coefficient of correlation r was -0,26, and 95% confidence interval (CI) for r was -0,47 to -0,015 (p=0,03). Univariate logistic regression showed significant association between WBC at W1 and Hb at M12 (OR 1,20; 95% CI 1,04 to 1,39, p=0,01). After the adjustment for donor's and recipient's age by transplantation and recipient's sex, multiple regression showed that WBC count remained predictive of anemia at M12 (OR 1,17; 95% CI 1,01 to 1,36, p=0,03). Early post-transplant inflammatory response predicts later anemia in kidney transplant recipients. An increase in WBC count in the first week post-transplant by 109/L increases the risk for anemia after twelve months by 17%.

M. Suljagić, P. Longo, L. Laurenti, D. Efremov

Abstract 887 CLL B-cells depend on various signals from the microenvironment for survival and proliferation. Among these, antigenic stimuli that are propagated through the B-cell receptor (BCR) are considered particularly important for the development and progression of CLL, suggesting that the BCR signaling pathway could be an important target for therapeutic intervention. We have previously characterized some of the critical components of the signaling pathway downstream of the BCR in CLL B cells and identified the protein tyrosine kinase Syk as a promising therapeutic target. In a recent study we showed that CLL B-cells frequently have increased basal/constitutive Syk activity and are moderately sensitive to the cytotoxic effect of the selective Syk inhibitor R406 [Gobessi et al , Leukemia 2009]. More importantly, the survival signal induced by sustained BCR engagement was completely abolished by R406, suggesting that this compound may exert an even greater effect in vivo by inhibiting antigen-dependent Syk activation. We have now tested this possibility in the Eμ-TCL1 transgenic mouse model of CLL. Aged Eμ-TCL1 mice develop CD5+ B-cell leukemias that, similar to aggressive human CLL, show features of an antigen-driven process, including expression of stereotyped BCRs and reactivity with common autoantigens and microbial agents [Yan et al , Proc Natl Acad Sci USA 2006]. For our experiments we used a TCL1 leukemia (TCL1-002) that does not grow in vitro , but can be propagated in syngeneic recipients in vivo . TCL1-002 cells express an unmutated stereotyped BCR encoded by the VH12/VK4 combination, which reacts with phosphatidylcholine, an autoantigen exposed on the surface of senescent erythrocytes. In vitro experiments showed that R406 is not cytotoxic for TCL1-002 cells, although it completely inhibited both the basal and BCR-induced activation of signaling pathways downstream of Syk. The absence of a direct cytotoxic effect provided a unique opportunity to investigate whether inhibition of BCR signaling will affect leukemia growth in vivo . For this purpose, 1×10 7 TCL1-002 cells were injected intraperitoneally in 18 syngeneic mouse recipients. Three days later treatment was started in 8 mice with R788, which is the water-soluble prodrug of R406, at a daily dose of 80mg/kg during 18 consecutive days. Because of the rapid clearance of the drug (serum half-life 6 /ml, range 12-300×10 6 /ml), whereas all R788-treated mice showed normal WBC numbers (median 6×10 6 /ml, range 3-8×10 6 /ml, P 50×10 6 /ml). Whereas all mice from the control group (n=9) died between 6 and 18 days from the beginning of therapy, 4 out of 9 mice from the R788 group survived for more than 33 days. The mechanism of R788 activity was primarily related to inhibition of leukemic cell proliferation, as evidenced by a substantial decrease in the percentage of Ki67-positive cells after 7 days of treatment (30% before, 5% after therapy, P To investigate whether R788 will also be effective against other TCL1 tumors we treated five TCL1 mice with preleukemic mono- or oligoclonal B-cell expansions during a four week period. R788 reduced the percentage of CD5+/B220+ cells in 2 cases, whereas in 2 other cases the percentage increased. Interestingly, the pattern of clonal Ig gene rearrangements changed during therapy, suggesting that only certain TCL1 clones are sensitive to R788 treatment. In summary, this study shows that R788 can effectively inhibit the growth of certain TCL1 tumors and provides the first in vivo experimental evidence suggesting that inhibition of antigen-dependent BCR signaling could be an effective therapeutic approach in CLL. Disclosures: No relevant conflicts of interest to declare.

L. Dizdarević-Hudić, Z. Kusljugic, Fahir Baraković, S. Brkić, Damir Sabitović, Elmir Jahić, Maida Isabegović, Elnur Smajić et al.

The aim of this study was to analyze (i) ratios between pro-inflammatory cytokines interleukin 6 (IL-6), interleukin 1 (IL-1), tumour necrosis factor alpha (TNF-alpha) and anti-inflammatory cytokine interleukin 10 (IL-10) in patients with acute myocardial infarction (AMI) and stable angina pectoris (ii) as well as correlation between IL-6 and IL-10 in AMI and (iii) correlation between IL-6 and lipoproteins in AMI.The total of 71 patients were enrolled in this study, 41 of them with AMI (study group) and 30 with stable angina pectoris (control group). The concentrations of cytokines and lipoproteins were measured from blood samples. Pro-inflammatory to anti-inflammatory cytokine ratios were calculated by dividing concentrations of pro-inflammatory cytokines with IL-10. In statistical analyses we used descriptive statistics, normality tests and analysis of correlation.IL-6: IL-10 ratio is significantly higher in AMI than in stable angina (P < 0,001), TNF-alpha: IL-10 is also higher in study group but the difference is not significant. We found positive linear correlation between IL-6 and IL-10 (r =0,43; p = 0,015) and negative linear correlation between IL-6 and high density lipoprotein HDL (r = -0,47; p= 0,008) in AMI.IL-6: IL-10 ratio is higher in AMI than in stable angina. There is linear correlation between IL-6 and IL-10 and IL-6 and HDL in AMI.

A. Macić-Džanković, Fuad Džanković, B. Pojskić, Z. Velija-Ašimi

The aim of this study was to examine the effects of hypoglycaemic drug-agonists of PPAR-gama receptors-rosiglitazone (Avandia,4 mg - Glaxo Smith Kline) on values of wide-spread risk - markers-fibrinogen, C-reactive protein and uric acid and glicolysated haemoglobin HbA1C as parameter of metabolic control .We included fourty patients with criteria for metabolic syndrome and evaluated results into groups of diabetic and prediabetic patients according to criteria of IDF (International Diabetic Federation)These risk markers and glicolysated haemoglobin HbA1C were observed at the start of therapy, then after four, eight and twelve weeks and results were compared and statistically calculated. Three months initial therapy with rosiglitazone significantly reduced values of HbA1C, fibrinogen and CRP but not uric acid in prediabetic patients.Rosiglitazone initial three months therapy significantly reduced HbA1C, fibrinogen and uric acid, but not CRP in diabetic patients.

H. Islami, Sadi Bexheti, R. Shabani, B. Nuraj, F. Zeqiri, A. Šukalo, I. Kurtishi, S. Kutllovci et al.

The role of meconium in the respiratory system was studied in newborns, who died from various causes (250 up to 3000 g of weight). We monitored tracheal rings response to dopamine, serotonin and ethanol in different concentrations (dopamine: 0,05 mg/ml, 0,5 mg/ml, 5 mg/ml; serotonin (5-HT): 10-4, 10-3, 10-2, 10-1 mol/dm3; ethanol: 0,02 ml, 0,5 ml, 1,0 ml; 96%). Tracheal smooth musculature tonus (TSM) was examined in 48 tracheal preparations taken after the newborn exitus due to different reasons. Based on functional researche of isolated preparations of tracheas, it may be concluded that: aspiration of meconium has not changed the response of TSM to dopamine, serotonin and ethanol (p>0,1) in comparison with the control group, which have died due to different lung inflammatory processes (e.g. pneumonia, bronchopneumonia, atelectasis, cerebral hemorrhage). The results suggest that meconium does not potentiate the constricting action of dopamine, serotonin and ethanol in tracheobronchial system. Meconium causes mild relaxation of the TSM through a mechanism that is not intermediated by the products of cyclooxygenases (prostaglandins, prostacyclins) from the tracheal epithelium or proteins. Also, as it seems, the direct activity of many tested acids in the smooth musculature has no significant impact on increase of the airways tonus in MAS syndrome.

Due to heightened risk for thromboembolic complications, nonvalvular atrial fibrillation (NVAF) presents an absolute indication for long-term oral anticoagulation therapy. This was an observational, analytical, randomised, one-year clinical study, conducted in the Blood Transfusion Institute Sarajevo, Bosnia & Herzegovina. The aim of this study was to present the oral anticoagulation treatment in terms of International normalised ratio (INR) monitoring and warfarin/acenocoumarol dose titration in 117 patients with NVAF. INR values, the doses of warfarin and acenocoumarol, as well as the tendency and adequacy of their changes were monitored. Percentages of the therapeutic INR values were 51,77% and 53,62%, subtherapeutic 42,84% and 35,86%, and supratherapeutic 5,39% and 10,53% for the warfarin and acenocoumarol treatment, respectively. The average total weekly doses (TWD) which most frequently achieved the therapeutic INR values were 27,89+/-12,34 mg and 20,44+/-9,94 mg, for warfarin and acenocoumarol, respectively. The dose changes with the INR values 1,7 or lower/3,3 or higher were omitted in 13,46% and 15,63%, and with the INR values 1,8-3,2 were noted in 8,62% and 13,48% of all the check-up visits in the warfarin and acenocoumarol group, respectively. The annual dose changes were noted in 24,65% and 31,41%, and the daily dose changes in 74,43% and 73,36% of all the check-up visits of warfarin and acenocoumarol group, respectively. We can conclude that the management of the oral anticoagulation treatment in our country is in accordance with the relevant recommendations, but with the present tendency toward underdosing and unnecessary frequent dose changing.

We investigate the global dynamics of solutions of four distinct competitive rational systems of difference equations in the plane. We show that the basins of attractions of different locally asymptotically stable equilibrium points are separated by the global stable manifolds of either saddle points or nonhyperbolic equilibrium points. Our results give complete answer to Open Problem 2 posed recently by Camouzis et al. (2009).

Shahzad Khan, A. Sabanoviç

Pushing micro-objects using point contact provides more flexibility and less complexity compared to pick and place operation. Due to the fact that in micro-world surface forces are much more dominant than inertial forces and these forces are distributed unevenly, pushing through the center of mass of the micro-object may not yield a pure translational motion. In order to translate a micro-object, the line of pushing should pass through the center of friction. In this paper, a semi-autonomous scheme based on hybrid vision/force feedback procedure is proposed to push micro-objects with human assistance using a custom built tele-micromanipulation setup to achieve translational motion. In the semi-autonomous pushing process, velocity controlled pushing with force feedback is realized along x-axis by the human operator while y-axis orientation is undertaken automatically using visual feedback. In this way the desired line of pushing for the micro-object is controlled to pass through the varying center of friction. Experimental results are shown to prove nano-Newton range force sensing, scaled bilateral teleoperation with force feedback and pushing operation.

P. Widimsky, W. Wijns, J. Fajadet, M. de Belder, J. Knot, L. Aaberge, G. Andrikopoulos, J. Baz et al.

Aims Patient access to reperfusion therapy and the use of primary percutaneous coronary intervention (p-PCI) or thrombolysis (TL) varies considerably between European countries. The aim of this study was to obtain a realistic contemporary picture of how patients with ST elevation myocardial infarction (STEMI) are treated in different European countries. Methods and results The chairpersons of the national working groups/societies of interventional cardiology in European countries and selected experts known to be involved in the national registries joined the writing group upon invitation. Data were collected about the country and any existing national STEMI or PCI registries, about STEMI epidemiology, and treatment in each given country and about PCI and p-PCI centres and procedures in each country. Results from the national and/or regional registries in 30 countries were included in this analysis. The annual incidence of hospital admission for any acute myocardial infarction (AMI) varied between 90–312/100 thousand/year, the incidence of STEMI alone ranging from 44 to 142. Primary PCI was the dominant reperfusion strategy in 16 countries and TL in 8 countries. The use of a p-PCI strategy varied between 5 and 92% (of all STEMI patients) and the use of TL between 0 and 55%. Any reperfusion treatment (p-PCI or TL) was used in 37–93% of STEMI patients. Significantly less reperfusion therapy was used in those countries where TL was the dominant strategy. The number of p-PCI procedures per million per year varied among countries between 20 and 970. The mean population served by a single p-PCI centre varied between 0.3 and 7.4 million inhabitants. In those countries offering p-PCI services to the majority of their STEMI patients, this population varied between 0.3 and 1.1 million per centre. In-hospital mortality of all consecutive STEMI patients varied between 4.2 and 13.5%, for patients treated by TL between 3.5 and 14% and for patients treated by p-PCI between 2.7 and 8%. The time reported from symptom onset to the first medical contact (FMC) varied between 60 and 210 min, FMC-needle time for TL between 30 and 110 min, and FMC-balloon time for p-PCI between 60 and 177 min. Conclusion Most North, West, and Central European countries used p-PCI for the majority of their STEMI patients. The lack of organized p-PCI networks was associated with fewer patients overall receiving some form of reperfusion therapy.

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