[Monoclonal Antibodies in the Treatment of Chronic Lymphocytic Leukemia in 2015]. / Monoklonální protilátky v lécbe chronické lymfocytární leukemie v roce 2015.

Chemotherapy combinations with monoclonal antibodies are now the basis for treatment of chronic lymphocytic leukemia. Rituximab, the most widely used anti-CD20 antibody in routine clinical practice, led not only to improvement of progression-free survival, but also to improvement of overall survival in previously untreated patients with good performance status in combination with fludarabine and cyclophosphamide. This regimen has become the standard treatment for patients in good physical condition. Rituximab and the newest anti-CD20 antibody obinutuzumab in combination with chlorambucil, as compared with chlorambucil alone, prolonged overall survival in previously untreated patients with significant comorbidities, and the combination of anti-CD20 antibody with chlorambucil has become the standard regimen in this group of patients. Alemtuzumab and ofatumumab improved treatment results in refractory chronic lymphocytic leukemia. Targeted therapy with combination chemotherapy and monoclonal antibody in patients with chronic lymphocytic leukemia represents a significant advance in the treatment of this disease.

Biological and clinical characteristics of patients with chronic lymphocytic leukemia with the IGHV3-21 and IGHV1-69; analysis of data from a single center.

This study aimed at mapping the frequency of IGHV3-21 and IGHV1-69 in a group of 417 patients newly diagnosed with chronic lymphocytic leukemia (CLL) and described basic characteristics, cytogenetic abnormalities and prognosis of these patient subgroups. IGHV3-21 was found in 29 patients (7%) and IGHV1-69 in 51 patients (12.4%). The median overall survival (OS) rates were 97 months and 85 months in the IGHV3-21 and IGHV1-69 groups, respectively. In this small group of patients, the study failed to show a difference in OS of IGHV3-21 patients with mutated and unmutated IGHV status (p<0.597). There was also no difference in OS between IGHV3-21 patients with mutated IGHV status and all patients in the group having unmutated IGHV status (p<0.245). On the other hand, patients with IGHV3-21 and the presence of some other adverse prognostic factors (age ≥ 65 years, lymphocyte count ≥ 50×109/L, serum thymidine kinase ≥ 9U/L, deletion of 17p) had statistically significantly worse OS than IGHV3-21 patients without the presence of these prognostic factors. The multivariate analysis of an entire group of Binet clinical stage A patients proved that the presence of IGHV3-21 is as an independent adverse prognostic factor even though there was no statistical difference in OS between patients with IGHV3-21 and those without IGHV3-21 in the entire group (p<0.769). Patients with IGHV1-69 had the same probablility of OS irrespective of the presence of other adverse prognostic factors; their OS was significantly shorter as compared with the other patients from the entire group (p<0.03).The study mapped the occurrence of recurrent cytogenetic changes detected by FISH in IGHV3-21 (subset #2 and non-subset #2) and IGHV1-69 and compared it with the occurrence of recurrent changes in the entire group of patients. In IGHV1-69 and in subset #2 IGHV3-21, higher proportions of deletion of 11q were found (30% and 31%, respectively), with the deletion being present in 19.2% of the entire group of patients. None of the 3 patients with IGHV3-21 and deletion of 17p had subset #2. Patients with subset #2 IGHV3-21 had higher proportions of deletion of 13 (69%) as compared with non-subset #2 IGHV3-21 patients (27%).

[Diagnosis of magnesium deficiency in the body, personal experience]. / Diagnostika deficitu horcíku v organismu, vlastní zkusenosti.

Magnesium as a component of a range of enzymatic systems is a very important intracellular cation in the organism. Its monitoring is limited in many observations only to determination of its concentration in blood serum. We have done an analysis of serum and erythrocyte magnesium concentrations in 23 healthy women, 70 healthy men and in 184 patients with ulcerative disease of gastroduodenum. It was proved in all the monitored groups that erythrocyte concentrations of magnesium were lower compared to values which were estimated from serum concentrations in 9 from 23 healthy women, in 3 from 60 healthy men, in 10 from 101 ill men with ulcerative gastroduodenal disease, and in 17 from 83 women with ulcerative gastroduodenal disease. The highest rate of low concentrations of erythrocyte magnesium in healthy women with physiologic concentrations of magnesium in serum was also confirmed by currently created subgroup of healthy women (n = 11) who undergone together with other analysis peroral Mg2+ load test. This test confirmed magnesium deficiency in 10 from 11 women. The results showed there are more frequent deficiencies of magnesium in organisms then it is generally assumed. They also proved the importance of nutrition and regular food in population of healthy, young women.

[Importance of determination of serum beta-2-microglobulin levels in patients with Hodgkin's lymphoma]. / Význam stanovení sérové hladiny beta-2-mikroglobulinu u nemocných s Hodgkinovým lymfomem.

The authors evaluated retrospectively in a group of 69 adult patients with Hodgkin's lymphoma the relationship between the beta-2-microglobulin serum level, basic demographic parameters (age, sex) and factors characterizing the extent (stage III and IV, "bulk" or mediastinal mass, number of affected areas of lymph nodes) and activity of the tumour (presence of B-symptoms, red cell sedimentation rate, haemoglobin, albumin and lactate dehydrogenase level, number of leucocytes and lymphocytes). They analyzed also the possible prognostic impact of beta-2-microglobulin on the therapeutic response risk of relapse and patient's survival. Methods of univariant statistical analysis confirmed the correlation of beta-2-microglobulin level with all investigated metric parameters of patients (advanced age, number of affected nodes, red cell sedimentation rate and lactate dehydrogenase level, lower albumin, haemoglobin level, numbers of leucocytes and lymphocytes). In multivariant analysis however the only independent metric markers significantly associated with an elevated protein level were more advanced age of the patients (P = 0.0002) and a lower number of leucocytes (P = 0.05). The values of beta-2-microglobulin was not influenced by the extent of the tumour (stage III and IV, "bulk" or mediastinal mass, higher number of affected areas of lymph nodes). Significantly more frequently elevated protein values were recorded in patients with manifestations of B symptoms associated with the diagnosis (P = 0.0003). Multivariant analysis did not prove the importance of the serum level of beta-2-microglobulin as a prognostic factor in the sense of predicted remission, development of a relapse or death in conjunction with progression of Hodgkin's lymphoma.

Contribution of comparative genomic hybridization and fluorescence in situ hybridization to the detection of chromosomal abnormalities in B-cell chronic lymphocytic leukemia.

BACKGROUND: B-chronic lymphocytic leukemia (B-CLL), the most common type of leukemia in Western Europe and the United States, is characterized by clonal chromosomal abnormalities detected in almost half of the studied patients. The precise determination of chromosomal changes helps to indicate the prognosis and to understand the pathogenesis of CLL. METHODS AND PATIENTS: We applied conventional cytogenetics (CC), FISH and comparative genomic hybridization (CGH) to the investigation of clonal abnormalities in 88 B-CLL patients at the time of diagnosis. RESULTS: By using CC of bone marrow cells without any stimulation, non-random chromosomal changes were found in 17 (19%) of 88 patients. The employment of FISH and CGH revealed chromosomal changes in additional 33 patients, thus increasing the detection rate of chromosomal abnormalities to 57%. The most common abnormalities detected in our patients included deletions of 13q in 16 cases (18%), followed by trisomy of chromosome 12 in 12 patients (13%), deletions of 11q in 10 patients (11%) and deletions of 17p in 10 patients (11%). A statistically significant correlation between higher disease activity and the presence of deletions 11q and 17p was observed. CONCLUSION: The addition of FISH and CGH to CC in 88 B-CLL patients improved the detection of clonal chromosomal changes from 19 to 57%. The most frequent chromosomal change was deletion of 13q14 (18%). Deletions of 11q23 and 17p13 were found in patients with higher clinical disease activity. Our results underline the importance of employing FISH and CGH techniques in CLL patients. CC without any stimulation has a low detection rate and is not suggested for detection of chromosomal changes in CLL.

[Transcutaneous oximetry in the diagnosis of ischemic disease of the lower extremities in diabetics]. / Transkutánní oxymetrie v diagnostice ischemické choroby dolních koncetin u diabetiku.

In diabetic patients with ischaemia of the lower extremities and mediocalcinosis the diagnosis of ischaemia is still difficult. One of the methods which give an objective idea of the microcirculation is transcutaneous oximetry. In the submitted paper the authors explain the principle and problems of assessment with recommendations for the practical application of the method, in particular in indication for angiography of the lower extremities in the presence of the diabetic foot syndrome with regard to probable spontaneous healing of defects and application of the method for following up the effect of revascularization operations.

[Methods in molecular cytogenetics for determination of prognostically important chromosome changes in patients with chronic lymphatic leukemias]. / Prínos metod molekulární cytogenetiky pro urcení prognosticky významných chromozomových zmen u nemocných s chronickou lymfatickou leukémií.

BACKGROUND: We applied classical cytogenetics, FISH and CGH to investigate prognostic important chromosomal changes, deletions of 17p, 11q and trisomy of chromosome 12 in 90 B-CLL patients at the time of diagnosis. METHODS AND RESULTS: Using classical cytogenetics the chromosomal changes were detected in 17 (18%) patients. Trisomy 12 was found in three patients, deletion 11q in two patients and deletion 17p in four patients. The employment of FISH and CGH revealed chromosomal changes in 52 (58%) patients, the trisomy of chromosome 12 was detected in 12 (13%) patients, the deletions of 11q and deletions of 17p in 10 patients (11%). Statistically significant correlation between higher disease activity and the stage of disease and the presence of deletion 11q and 17p was found. The trisomy of chromosome 12 was found in patients with abnormal markers and in patients with higher stage of the disease. CONCLUSIONS: According to our results, the majority of chromosomal abnormalities in B-CLL may escape detection when classical cytogenetics is the only diagnostic technique used. It stresses the importance of employing additional techniques including FISH and CGH at the time of diagnosis.

Markedly eccentric peripheral vascular stenoses: percutaneous atherectomy with an endomyocardial biopsy device.

In 23 patients, percutaneous atherectomy was performed with an endomyocardial biopsy device in 27 eccentric stenoses of lower limb arteries. The mean percentage stenosis was reduced from 82% to 14% (P: <.001). Histopathologic examination revealed no media or adventitial tissue in the extracted particles. The technical success and complication rates were similar to those reported for conventional percutaneous transluminal angioplasty of short symmetric lesions.

[Rheological properties of blood during pulsatile pharmacomechanical and continuous local thrombolysis]. / Reologické vlastnosti krve pri pulzní farmakomechanické a lokální kontinuální trombolýze.

BACKGROUND: The aim of the work was to find out whether the controlled administration of a thrombolytic directly into the arterial occlusion could prevent formation of the systemic lytic state, which may result in distant bleeding complications. METHODS AND RESULTS: In patients subjected to pulsatile pharmacomechanical (94 patients) and local continual thrombolysis (74 patients) changes in blood and plasma viscosity, coagulation tests, fibrinogen levels and some other parameters were investigated. CONCLUSIONS: Pulsatile pharmacomechanical thrombolysis, similarly to other forms of thrombolysis, is accompanied with systemic lytic state and the risk of unwanted resorption of the hemostatic thrombosis. Urokinase administration brings about regress of systemic changes, which is similar to the use of either tested thrombolytic administration. As treatment by the continual thrombolysis takes is approximately 40 times longer, the risk of systemic lytic state and bleeding complication growths.

[Effect of temperature on rheologic properties of blood and internal viscosity of erythrocytes]. / Vliv teploty na reologické vlastnosti krve a vnitrní viskozitu erytrocytu.

BACKGROUND: The blood viscosity is one of the factors affecting tissue blood flow. Aim of the study was to establish how the blood viscosity and internal viscosity of the red cell (Tk) may be influenced by change of the temperature. METHODS AND RESULTS: We have measured plasma and blood viscosity in 20 samples of human plasma and 17 samples of human blood. Viscosity was established with rotational viscometer under the temperature ranging from 25 degrees C to 45 degrees C. Concomitantly the internal viscosity of the red cell (Tk) was estimated. Plasma and blood viscosities are decreasing with the temperature elevation but the change is not linear through temperature range used for testing. The most pronounced change was found in relatively lower temperatures. Relative viscosity of the blood did not change significantly with the temperature except of measurements under low shear conditions performed in low temperature. Relative blood viscosity increased with temperature fall in such a situation. The internal viscosity of the red cell (Tk) increased significantly with temperature elevation. CONCLUSIONS: The average values of the blood and plasma viscosity fell with temperature elevation but the change was not linear. The plasma viscosity change was the highest in the low temperature range. These findings together with significant differences between relative and dynamic blood viscosity in low shear conditions and in 25 degrees C showed that blood viscosity was influenced by qualitative changes of the plasma followed by higher aggregation of the red cells.

[The effect of heparan sulfate on percutaneous transluminal angioplasty in the vessels supplying the lower extremities]. / Vliv heparansulfátu na efekt perkutánní transluminální angioplastiky v oblasti tepen zásobujících dolní koncetiny.

BACKGROUND: The condition of patients after percutaneous transluminal angioplasty is influenced among others by the subsequent development of restenoses and reocclusions. The objective of the submitted work was to assess whether oral administration of heparan sulphate can influence the development of restenoses after percutaneous transluminal angioplasty in the pelvic and femoropopliteal region. METHODS AND RESULTS: 102 patients (78 men and 24 women, age 42-86 years) were divided into four groups. Percutaneous transluminal angioplasty was performed either on account stenosis in the aortoiliac or femoropopliteal area. (The original number was 115 patients, 13 patients were eliminated: the reasons were technical failure of the intervention procedure, reocclusion, the patient was lost from records.) As antiaggregant the patients were given acetylsalicylic acid, 250 mg/day: patients included in the heparan group were given heparan sulphate (Hemovasal, Manetti and Roberts) 100 mg/day for a period of 3 - 4 months. As compared with controls, the patients treated with heparan sulphate had within the 3 - 4 month period a significantly longer claudication distance (p < 0.05), a higher Doppler index (p < 0.05) and maximal blood flow in the feet. CONCLUSIONS: Heparan sulphate administration to patients after percutaneous transluminal angioplasty on account of stenosis of the aortoiliac or femoropopliteal area improves some angiological parameters which can suggest a slighter tendency of early restenosis.

Percutaneous transluminal angioplasty of the deep femoral artery.

Percutaneous transluminal angioplasty (PTA) of the deep femoral artery (DFA) was performed in 21 patients with chronically occluded superficial femoral artery (SFA) and a significant DFA lesion as documented by arteriography. The authors failed to pass the guidewire through the occlusion in two patients. The results do not include another patient who, while the PTA was technically successful, had to have a limb amputated because of skin lesion infection. The remaining 18 patients showed a significant increase in the ankle-arm pressure index, prolongation of the claudication interval and reported subjective improvement immediately after PTA; plethysmography performed in 14 patients revealed a significant increase in maximum foot blood flow. While the claudication intervals were found to have further significantly prolonged 6-12 months following PTA, the ankle-arm pressure index remained unchanged. There were no serious complications during and after the PTA procedure. In patients with both superficial and deep femoral artery involvement, where SFA PTA is not suitable or feasible, PTA of the DFA seems to be the method of choice. Considering its probable clinical benefits, it is appropriate to attempt it even in cases where the chances of technical success are low.