Chronic lymphocytic leukemia (CLL) is characterized by extraordinary heterogeneity in terms of clinical course with overall survival ranging from several months to dozens of years. It is currently not possible to accurately predict the future clinical course in an individual patient. Angiogenesis has been recently reported as a potential prognostic factor in various hematological malignancies including CLL. The objective of the present study was to quantify plasma levels of key angiogenic activators vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in patients with CLL and determine their potential change after intensive fludarabine-based treatment. Peripheral blood EDTA plasma concentrations of bFGF and VEGF were measured using comercially available enzyme-linked immunosorbent assay in 73 patients with untreated CLL (43 males, 30 females, median age, 65 years, range 31-88) and 80 healthy donors serving as control group. We found statistically significant increase in concentrations in patients with chronic lymphocytic leukemia compared to the control group (p < 0.0001 for both cytokines). No differences in angiogenic factors were noted between subgroups with low vs. intermediate vs. high-risk stage according to modified Rai staging or males vs. females. In twelve patients who achieved at least partial response after intensive fludarabine-based treatment, levels of bFGF as well as VEGF decreased significantly (bFGF, p = 0.0005; VEGF, p = 0.0068); in addition, they were no more significantly different from controls (bFGF, p = 0.524; VEGF, p = 0.728). Our data showed that key angiogenic activators bFGF and VEGF were elevated in plasma ofCLL patients. Furthemore, treatment with intensive fludarabine-containing regimens resulted in significant decrease of both cytokines. These data suggest that angiogenic cytokines may indeed play a significant role in CLL biology and that treatment with combination of fludarabine, cyclophosphamide +/- rituximab may exhibit antiangiogenic properties. Further studies with longer follow-up are necessary for evaluation of a possible association between angiogenic markers and progression-free survival or overall survival.

Anagrelide hydrochloride is an effective drug used in patients with ET and other myeloproliferative disorders with thrombocythemia to selectively decrease the number of thrombocytes. Indications for use of anagrelide were described in detail in Czech medical literature. Since 2005 data concerning treatment with anagrelide in some medical clinics have been collected in patient register showing course of treatment from 2004, when the medicament obtained marketing authorization from State Institute for Drug Control to be used in the treatment of thrombocythemia in myeloproliferative disorders. Aim of patient register is to monitor medical effect of anagrelide therapy and incidence of adverse effects in patients with ET and other myeloproliferative disorders and subsequent analysis of collected data. At the moment patient register contains data from 154 patients.

The in vivo effects of the hypolipidemic drug clofibrate (0.5 mmol/kg body wt daily p.o. for 7 days) on serum lipids and apolipoproteins have been studied in male rats. Clofibrate caused an increase in liver weight without affecting body weight. Triglyceride, total and free cholesterol and HDL cholesterol were decreased in sera of clofibrate-treated rats. The relative abundance, and accordingly the absolute quantities, of the polyunsaturated fatty acids linoleic (18 : 2), linolenic (18 : 3) and docosahexenoic (22 : 6) in serum triglyceride decreased in response to clofibrate treatment. The concentrations of serum apolipoproteins A-I, B and C-III were reduced in clofibrate-treated rats. The apolipoprotein E level was not altered. The distribution of apolipoproteins A-I, B, C-III and E between heparin-Mn supernatant and precipitate were unaffected. The unchanged C-III distribution indicates unaltered intravascular VLDL catabolism. Concurrent reductions in serum HDL cholesterol and ApoA-I in clofibrate-treated rats suggest a diminished production of lipoprotein particles containing ApoA-I. Reductions in serum ApoB and in the mass ratio of serum triglyceride to ApoB indicate a decrease in the number and size, respectively, of circulating triglyceride-rich lipoprotein particles. These observations suggest that the hypolipidemic effect of clofibrate in the normolipemic rat is caused mainly by diminished hepatic secretion, rather than by enhanced catabolism, of triglyceride-rich lipoproteins.

Autoři uvaději kazuistiku kryptokokozy u nemocneho s progredujici chronickou B-lymfatickou leukemii.

The authors present an account of a young woman who developed an acute cerebellar infarction where systematic search of the etiology of the cerebral affection revealed malignancy of the mammary gland. The authors discuss basic pathogenetic mechanisms of the development of cerebral infarction in patients with carcinoma.

In a group of 993 patients with serious medical diseases an important deficiency of antithrombin III was found in patients with hepatic insufficiency, pulmonary embolism and with disseminated intravascular coagulation. Acquired antithrombin III deficiency in these conditions develops when the antithrombin production in the liver is low and also in patients with shock syndrome and disseminated intravascular coagulation. Assessment of antithrombin III is of diagnostic and prognostic value in thrombotic and prethrombotic conditions and its results is decisive for adequate substitution. Adequate AT III substitution without concurrent heparin administration in patients with septicaemia and manifestations of DIC improves the prognosis of patients with an increased endothelial resistance.

The authors revealed some changes in the platelet activity in patients with invasive cardiological procedures. Changes of the platelet function were manifested by an enhanced aggregation of platelets in vivo, an increased secretion from alpha granules and increased release of prostaglandin metabolites from platelets and from the vascular wall. Acetylsalicylic acid (ASA) suppressed the formation of circulating platelet aggregates in vivo, but the platelet activity was manifested by another mechanism, independent on ASA. The authors recorded therefore an increase of prostaglandin metabolites and PF4 even in patients who were treated with ASA before the invasive examination.

The authors used the Simplate test (Organon Teknika) to examine the bleeding time from an incision in 15 healthy blood donors and found normal values of 3.45 +/- 0.90 min. The authors proved a close correlation between the improvement of the number of platelets in 10 patients with thrombocytopenia, treated with thrombocyte infusions and the improvement of the bleeding time when using the Simplate R test after one hour and after 24 hours following thrombocyte administration. Examination of the bleeding time by means of the Simplate R test (Organon Teknika) was well tolerated by the authors' patients and the test does not produce any side-effects.

We analysed 22 patients suffering from migraine to evaluate the possible activation of platelet function utilizing the following methods: platelet factor 4, thromboxane B2 and 6 - keto prostaglandin F 1 alpha levels in platelet poor plasma. Laboratory tests were performed on all patients during headache-free period and the results obtained were compared with those of a normal healthy individuals. The mean results obtained in the patients group during pain-free period indicated a significant activation of platelet function when compared with the normal group.

Bohuslav Melichar, MD, Second Department of Internal Medicine, Charles University Medical School, Pospisilova 365, CZ500 36 Hradec Kralove (Czech Republic) In recent years, there have been several reports of increased concentrations of cytokines as well as other indicators of immune activation, e.g. soluble interleukin-2 receptor or neopterin, in patients with lymphoma [1-7]. Among other immunological disturbances, increased immunoglobulin E (IgE) levels have also been reported [8]. IgE synthesis is known to be induced by interleukin-4 (IL·4) and inhibited by interferon-γ (IFN-γ) [9], and elevated IL-4 levels have been reported in some conditions characterized by increased IgE concentrations, e.g. atopic disorders [10]. A rise in serum IL-4 has also been described in other disorders, notably in cutaneous T cell lymphoma [11]. We assayed plasma concentrations of IL-4, IFN-γ and IgE in 14 patients with a histologically confirmed diagnosis of lymphoma (mean age 42 ± 17 years, table 1) and in 15 healthy controls (10 males and 5 females, mean age 48 ± 20 years, range 21-75). All patients had active disease and were either newly diagnosed or untreated for at least 4 weeks. A plasma sample was obtained and kept frozen at -45 °C until assayed. IL-4 and IFN-γ were determined using commercial ELISA kits (Quantikine human IL·4, R&D Systems, Minneapolis, Minn., USA, and Endogen human IFN-γ, Boston, Mass., USA) according to the manufacturer’s instructions. IgE was measured with a nephe-lometric method using a commercial kit (Behring, Marburg, Germany). The limits of detectability were 10 pg/ml for IL·4 and IFN-γ and 33 IU/ml for IgE. The results were expressed as mean, standard deviation and range of values, the statistical comparison was performed with the Mann-Whitney U test and the correlations were studied with the Spearman rank coefficient. Significance was based on the p = 0.05 level.

The authors draw attention to the leukostasis syndrome which develops in haematological patients in case of enormous leucocyte proliferation. It occurs most frequently in chronic myelosis but may occur also in other types of leukaemia. The diagnosis is not easy. Most frequently disorders of the microcirculation develop in the lungs and brain. These are frequently very urgent clinical situations which can be resolved by leukapheresis. The authors described a patient where during chronic lymphadenosis proliferation of lymphocytes occurred to values of 1432 x 10(9)/l. After leukapheresis and cytostatic treatment rapid improvement of the condition occurred and the leucocyte values were approximately 30 x 10(9)/l. The patient's condition improved for a long period of time and became stabilized.

Authors document with the aid of fluorescent angiography of the retina pathological changes on the retina resulting from hyperviscous syndrome of Waldenstrom macroglobulinemia and their regulation after combined treatment with plasmapheresis and cytostatics.

The authors made 184 thrombocytaphereses for the preparation of thrombocyte concentrates on a Travenol CS-3000 separator. They evaluate indicators on which the thrombocyte yield depends: it was found that the yield is higher in donors with a higher number of platelets and that it increases with the period of separation. The mean thrombocyte yield was 2.91 +/- 0.84 x 10(11). It corresponded to the average lower platelet number of donors--182 x 10(9)/L. In those donors where the number of platelets was higher than 180 x 10(9)/L, the yield was 3.21 x 10(9)/L. The undesirable presence of leucocytes (in 98% lymphocytes) increases in relation to the number of leucocytes in the donor and their decline after separation. It was lower in longer separations. The authors discuss the possibility to increase the thrombocyte yield without contamination with leucocytes.

The submitted work was concerned with two problems: a) investigation of the dynamics of changes of the fibrinogen and fibrin breakdown products after a single dose of streptokinase, b) evaluation of the effectiveness of thrombolysis from changes in the fibrinogen concentration. Two groups of patients were examined with the Q form of acute myocardial infarction who were treated at an intensive care unit. The first group comprised 62 patients (mean age 56.3 years) who were given 1 million units of streptokinase by the i.v. route. The second group comprised 52 patients who were given 1.5 million units of streptokinase. The authors investigated the fibrinogen plasma concentration and the fibrin breakdown product concentration in serum after 3-hour intervals. Concurrently they examined the creatine kinase curve. They proved a significant increase of the fibrinogen and fibrin degradation products before thrombolysis (p less than 0.001). The fibrinogen concentration declined in both groups highly significantly with a maximum after 12 hours. The fibrinogen level reached normal levels in both groups after cca 24 hours. Patients with a high initial fibrinogen level (above 5 g/l) did not attain hypofibrinogenic values during thrombolysis. This phenomenon did not depend on the size of the streptokinase dose. The decline of fibrin breakdown products in both groups declined to baseline values within 24 hours. The authors confirmed that the effectiveness of thrombolysis is influenced among others also by the residual fibrinogen value.

During intensive treatment of haemoblastoses it is important to administer repeatedly high-quality platelet concentrates. The authors describe the first results obtained with the use of an isoradial chamber of Travenol Co. for separation on a CS-3000 separator. Using the chamber, they achieved in the first 20 patients a reduction of the separation time by 30 mins. (23%) and the thrombocyte yield was not reduced. The resulting product contained, however, more leucocytes. The chamber can be used to reduce the separation period also under Czechoslovak conditions where donors have smaller numbers of thrombocytes than reported by western authors (the microcomputer of the separator is set for a regime suited for larger thrombocyte numbers).

The authors performed 1252 haemaphereses, incl. 689 plasmaphereses. They divide the side-reactions as follows: Technical reaction: these do not threaten the donor directly; these reactions were recorded in 4.4%. Clinical reactions--total 6.8%. a) early, b) late. The authors recorded one severe reaction during plasmapheresis, there was however, no fatality. The most frequent reactions were: general symptoms, failure to withdraw blood because of poor state of the veins and hypotension. The authors analyze the importance of the observed reactions. They used continual separators where in general the incidence of reactions is smaller. They investigated also late reactions, in particular after development of infections in donors or in the staff working with the separator. Repeated donors were subjected to detailed immunological examination, no abnormalities were, however, recorded.

Severe inhibition of haematopoiesis is a serious disease from the prognostic aspect. The authors evaluated a group of 26 patients of whom one survived for more than five years. The mean life span is 154 days. The most frequent cause of death are infectious complications, in particular septicaemia. Investigation of the aetiology of the disease was negative in 46% of the cases, in the remainder drugs were suspected most frequently, in particular antibiotics. It is very important to prevent the development of secondary inhibition of haematopoiesis, in particular by careful indication of myelotoxic drugs. In case of necessity, these drugs should be administered for a short time, in the lowest effective doses with check-ups of the haemogram. Hope for affected patients in future is transplantation of bone marrow and the early administration of antilymphocytic globulin.