[Hemostasis in patients with acute leukemia treated with high doses of cytosine-arabinoside: the effect of chemotherapy and infectious complications on hemostasis]. / Hemostáza u nemocných s akutní leukémií lécených vysokými dávkami cytosin-arabinosidu: vliv chemoterapie a infekcních komplikací na hemostázu.

Haemostatic parameters were studied in 12 adult patients with acute myeloid leukaemia and acute lymphoblastic leukaemia in complete remission using high-dose cytosine arabinoside regiments together with with other drugs. Increased tissue plasminogen activator (t-PA:Ag) antigen 4 hours after AraC application (p < 0.05) as well as increased levels of plasminogen activator inhibitor activity (PAI) (p < 0.05) and fibrinopeptide A (FPA) antigen (p < 0.05) were observed on day 2. All patients during bone marrow aplasia suffered from infectious complications (7 from sepsis and 5 from fever of undetermined origin). During that period of infection the increased levels of FPA on day 21 (p < 0.05), PAI on days 15 and 21 (p < 0.05) and fibrinogen on day 21 (p < 0.05) as well as decreased values of antithrombin III (p < 0.05) on day 21 and protein C on day 15 (p < 0.05) were measured. t-PA:Ag, plasminogen, alpha 2 antiplasmin and fibrin(ogen) degradation products were within normal throughout infectious complications. None of the patients experienced clinically manifest thrombotic complication. Though the results demonstrate that changes found were not clinically important (even if they were statistically significant), and that haemostasis was compensated as well as that thrombosis was not serious problem, authors recommend routine haemostasis monitoring in acute leukaemia patients, especially at diagnosis, in association with chemotherapy and during infectious complications.

The influence of induction chemotherapy and remission status on haemostasis in patients treated for acute myeloid leukaemia.

Haemostatic parameters were studied in 31 adult patients treated for acute myeloid leukaemia (AML) using the 3 + 7 regimen. Lower values of antithrombin III (AT-III), alpha 2-antiplasmin (alpha 2AP) and plasminogen were observed on days 8 and 14 (P < 0.05). Fibrinopeptide A (FpA) levels were higher at diagnosis (P < 0.05), increased again during chemotherapy on days 4 and 8 and eventually returned to the normal range. Tissue plasminogen activator, plasminogen activator inhibitor, protein C and fibrin(ogen) degradation products were normal throughout the period of observation. Complete remission (CR) was achieved in 19 of 31 patients (61%). In order to compare haemostatic changes in CR patients with those in refractory cases, patients were divided into two groups. In patients with refractory AML (n = 12) AT-III, plasminogen and alpha 2 AP were significantly lower than in those in CR. FpA levels were increased in all patients at diagnosis. This elevation progressed in both groups during chemotherapy (on days 4 and 8) and then normalized only in patients in CR. However, in resistant patients, higher FpA values persisted or even increased further on day 14. The fact that none of our patients suffered from clinically manifest thrombotic complications suggested that haemostasis was well compensated and the observed changes were of no clinical importance, even if they were significant statistically.

[The significance of plasminogen activator inhibitor 2 in patients with hematologic malignancies]. / Význam inhibitoru aktivátoru plazminogenu 2. typu u nemocných s hematologickými nádory.

The authors investigated the incidence of the plasminogen activator inhibitor-2 (PAI-2) in 88 patients with haematological tumours. In four patients (4.5%) an elevated PAI-2 level was found: in patient (no. 1) with non-differentiated leukaemia which developed as a result of transformation of myelodysplastic syndrome, in a female patient (no. 2) with non-differentiated blastic crisis of chronic myeloid leukaemia, in a female patient (no. 3) with acute monocytic leukaemia (M5) and in a pregnant female (patient no. 4) with a malignant lymphogranuloma. In none of the other patients with another type of acute myeloid leukaemia or other haematological tumours PAI-2 was detected. High PAI-2 levels after successful cytostatic treatment and attainment of complete remission reached normal levels, during a relapse high PAI-2 levels were recorded again. The authors assume that the presence of PAI-2 may suggest a monocytic origin of the cells which produce it. They conclude also that its value may reflect the activity of the disease with high levels during presentation or relapse of the disease and a drop or disappearance of PAI-2 after successful treatment and achieved remission.

[Results of studies of indicators of hemostasis in hemodialyzed patients during administration of 1-deamino-8-D-arginine vasopressin]. / Výsledky vysetrení nekterých ukazatelu hemostázy u hemodialyzovaných nemocných pri podání 1-deamino-8-d-arginin vasopresinu.

The fibrinolytic activity (FA) evaluated according to the euglobulin clot lysis time was in haemodialyzed patients (3.0 +/- 0.2 arb. u.) lower than in patients with chronic renal failure treated by conservative methods (4.7 +/- 0.6, p less than 0.05) and than in healthy subjects (4.2 +/- 0.4, p less than 0.05). After stimulation by intravenous administration of 1-deamino-8-D-arginine vasopressin the FA in haemodialyzed patients rose to (4.5 +/- 1.6), less than in conservatively treated (14.1 +/- 2.1, p = 0.06) and than in healthy subjects (18.2 +/- 3.9, p less than 0.001). By using specific methods it was proved that the inadequate rise of FA in haemodialyzed patients after stimulation is conditioned by a defect of the release of the plasminogen tissue activator from the vascular wall. Contrary to healthy subjects (7.0 +/- 1.3 vs. 16.7 +/- 2.3 ng/ml, p less than 0.01) is plasma concentration in haemodialyzed subjects (5.3 +/- 0.5 vs. 7.9 +/- 0.8, NS) did not increase significantly. Repeated examinations of some of the haemodialyzed patients revealed that almost 20 months of regular haemodialysis do not lead to further changes of basal (2.9 +/- 0.3 vs. 2.8 +/- 0.2) nor stimulated (4.2 +/- 0.5 vs. 4.8 +/- 0.9) FA. Basal plasma concentrations of the von Willebrand factor were in the dialyzed patients (89.1 +/- 8.8%) higher than in healthy subjects (67.2 +/- 4.4, p less than 0.05). After stimulation the concentration of the von Willebrand factor increased significantly in healthy subjects (99.1 +/- 4.3, p less than 0.01), but not in dialyzed patients (82.9 +/- 3.1, NS), obviously due to the pathological reactivity of their vascular wall. The above findings may be associated with thromboses and atherosclerosis in patients on long-term dialysis.

[The effect of isradipine (Lomir, Sandoz) on coronary insufficiency during the esophageal stimulation stress test]. / Ucinky isradipinu (Lomir, Sandoz) na koronární nedostatecnost pri zátezové jícnové stimulaci.

The new calcium antagonist, the dihydropyridine derivative isradipine (Lomir, Sandoz) is used above all in the treatment of hypertension. During oesophageal stimulation the authors proved its very favourable effect also in patients with coronary insufficiency during exertion. A single oral dose of 7.5 mg of isradipine led in all 14 examined patients to increased tolerance of exertion; in 36% of the patients after administration of the drug coronary insufficiency was no longer found. In the remaining patients the incidence of coronary insufficiency was shifted to higher frequencies. The authors recorded a drop of systolic and diastolic pressure during exertion, during rest as well as during recovery. No undesirable effects nor hypertension were present. The drug is a useful preparation in particular in hypertonic patients with angina on exertion.

[Injections of mitoxantrone, VUFB Praha, in the treatment of acute myeloid leukemia and non-Hodgkin's lymphoma]. / Mitoxantron injekce VUFB Praha v lécbe akutních myeloidních leukémií a nehodgkinovských lymfomu.

Mitoxantrone injections (Mx), VUFB Prague, were administered to 24 patients with acute myeloid leukaemia (AML) and non-Hodgkin lymphoma (NHL). Patients with NHL were treated by monotherapy with Mx or by polychemotherapy in combination with CMOP (cyclophosphamide, mitoxantrone, vincristine, prednisone). To patients with AML Mx was administered 1x during induction treatment as monotherapy, in the remaining nine patients as post-remission treatment or re-induction treatment in combination with medium doses of cytosine arabinoside (IDAC + Mx). A positive therapeutic effect was observed in NHL with a high or medium degree of malignity during primary as well as during secondary treatment. Very good therapeutic results with Mx were achieved in AML in induction, post-remission and even re-induction treatment with a minimal haematological and non-haematological toxicity.

Electrophysiological effects of oral isradipine (Lomir, Sandoz).

Electrophysiological effects of oral isradipine were studied. There are controversial references about the presence of its selective negative chronotropic influence from in vitro and in vivo studies using intravenous route. The authors administered 7.5 mg and 2.5 mg of isradipine orally in two groups of patients. Electrophysiological parameters were measured by use of the transoesophageal atrial pacing prior to the administration and 120 minutes after it. Significant fall in blood pressure was observed in both groups. Changes of atrioventricular nodal parameters such as stimulus-R interval. Wenckenbach point and probable effective refractory period of atrioventricular node showed positive dromotropic effect on artioventricular conduction, but the negative chronotropic action was not proved. On the contrary, the mean sinus cycle length shortened significantly in both groups and the maximal sinus node recovery time decreased after isradipine. The extent of changes of both sinus and atrioventricular nodal parameters is similar and is not consistent with selective effect of isradipine on sinus node.

[Disorders of fibrinolysis and thrombophilic states, risk factors and possibilities of dietary effects]. / Poruchy fibrinolýzy u trombofilních stavu, jejich rizikové faktory a moznost ovlivnení dietou.

An inadequate efficiency of the fibrinolytic system was revealed in 50-60% of subjects suffering young age from venous thrombosis or myocardial infarction. In a group of 27 patients with the history of deep venous thrombosis of the idiopathic type the authors revealed a significant relationship between the elevated body weight and inadequate fibrinolysis manifested by a reduced fibrinolytic capacity and excess inhibitor of plasminogen activator and its inadequate decline after desmopressin infusion (DDAVP). In a group of 29 patients, who had suffered a myocardial infarction when young, the authors revealed a significant association between reduced fibrinolytic capacity and elevated body weight, hypertriglyceridaemia and increased immunoreactive insulin secretion after a glucose load. In half the investigated subjects it proved possible to improve the reduced fibrinolytic capacity by a low energy diet.

[Changes in hemostasis in blood donors on the Fenwal CS 3000 separator]. / Sledování zmen hemostázy u dárcu na separátoru FENWAL CS 3000.

During thrombocytophereses on a blood cell FENWAL CS 3000 separator in one group of donors the anticoagulant solution ACD-A recommended by the manufacturer was used, in the other group of donors ACD-A with heparin was used. The authors give an account of the changes in some parameters of haemostasis in these donors on the separator incl. examination of fibrinopeptide A which is the most sensitive indicator of clotting activity during separation. Heparin administration prevented a rise of fibrinopeptide A and did not lead to a reduced platelet yield.

[The effect of HLA alloimmunization and other factors on the effectiveness of thrombocyte concentrates]. / Vliv HLA aloimunizace a dalsích faktoru na úcinnost trombokoncentrátu.

Sixteen patients with severe thrombocytopenia and secondary bone marrow inhibition were given 81 thrombocyte concentrates. In 55.6% platelet transfusions led to an adequate posttransfusion rise of platelets, in 44.4% of thrombocyte transfusions the increase of platelets was not satisfactory. The cause of the inadequate posttransfusion rise of platelets in 19.4% were antibodies against HLA antigens. In addition to other known factors which influence the rise of platelets a significant relationship was revealed between administration of Amphotericin B, broad spectrum bactericide antibiotics and the body temperature. To improve substitution of thrombopenic patients by platelet concentrates the authors recommend to create a national register of HLA typed donors.

[Pure red cell aplasia in chronic lymphatic leukemia. Successful treatment using immunosuppression]. / Cistá aplázie erythropoézy u chronické lymfatické leukémie. Uspesná lécba imunosupresí.

The authors describe two cases of chronic lympocytic leukaemia complicated by pure red cell aplasia of autoimmune origin. The first patient achieved complete recovery of erythropoiesis after short-term immunosuppression by means of cyclophosphamide and prednisone. The second patient did not respond to the same combination of immunosuppressive drugs and remission was achieved by administration of antithymocyte globulin. In the discussion the authors deal with contemporary knowledge of the pathogenesis of autoimmune erythroblastopenia and mechanismus of action of antithymocyte globulin.

[Treatment of myelodysplastic syndrome using continual subcutaneous infusion of low doses of cytosine arabinoside]. / Lécba myelodysplastického syndromu kontinuální podkozní infúzí nízkých dávek cytosin arabinosidu.

The authors summarize their experience with the administration of small doses of cytosine arabinoside continuously by subcutaneous infusion in 13 patients with myelodysplastic syndrome. Alcysten Spofa was administered in doses of 20 mg/sq.m per day for 5-17 days in one cycle. A total of 26 therapeutic cycles were administered. Favourable responses were obtained in four patients, partial results were achieved in two patients; in seven instances treatment produced no response. The authors compare also the results obtained in this group with a previous group of 11 patients treated with small doses of cytosine arabinoside, which was administered intermittently, i.e. twice a day by the subcutaneous route. Continuous administration did not produce more favourable therapeutic results, it caused however a larger number of infections and haemorrhagic complications as compared with intermittent administration. The authors recommend administration of small doses of cytosine arabinoside in patients with prognostically adverse types of myelodysplastic syndrome - intermittently 10 mg subcutaneously twice a day for 14-21 days.

Use of radionuclides in the diagnosis of thromboembolism of venous origin: its potential and limitations. A review.

The review discusses the potential and limitations of radionuclide (RN) techniques of examination in diagnosing thromboembolic disease of venous origin. The advantages and drawbacks of perfusion pulmonary scintigraphy as the most commonly used method are weighed especially with a view to the diagnosis of pulmonary embolism (PE). The need for a combined examination including inhalation scintigraphy and chest X-ray is underlined. The criteria for interpreting results of RN techniques of examination in assessing the presence of PE are defined. Of the methods used in the diagnosis of venous thrombosis, the benefits and limitations of the fibrinogen uptake test (FUT) and radionuclide venography (RNV) are pointed out. When comparing RNV with X-ray phlebography, the authors found a low sensitivity in the crural area (54%) and, on the contrary, a 100% agreement in the areas of iliac veins and the vena cava inferior.

[Treatment of medium and highly malignant non-Hodgkin's lymphoma with combined chemotherapy using methotrexate, adriamycin, cyclophosphamide, vincristine, prednisone and bleomycin (protocol MACOP-B)]. / Lécba stredne a vysoce maligních nehodgkinských lymfómu kombinovanou chemoterapií metotrexátem, adriamycinem, cyklofosfamidem, vinkristinem, prednisonem a bleomycinem (protokol MACOP-B).

Combined chemotherapy, protocol MACOP-B, was administered to 21 patients with non-Hodgkin lymphoma (NHL) with a medium or high grade of malignity, clinical stage II-IV. Complete remission was achieved in 17 patients (81%), in one instance partial remission was induced. One patient died from a cardiovascular and one from a thromboembolic complication during treatment. In one patient the results were not evaluated. Three patients developed severe granulocytopenia which called for reduction or delay of treatment and a septic condition developed. In addition to myelosuppression the main complications were stomatitis and mycosis. No death caused by infectious or haemorrhagic complications was recorded. The described chemotherapy is recommended in particular in immunoblastic lymphomas, diffuse lymphomas from cleaved and non-cleaved cells and diffuse lymphomas with mixed cellularity.

[Comparison of radionuclide venography with roentgen phlebography]. / Srovnání radionuklidové venografie s rtg-flebografií.

The authors evaluated a group of 78 patients where in addition to radionuclide venography (RNV) also X-ray phlebography was used (RTGF) within a time interval of not more than 72 hours. The results of 102 examinations were compared, 276 areas were correlated at six different sites. Agreement was recorded in 249 instances (90%), a false negative finding in 23 (8%) and a false positive finding in 4 (2%). Sensitivity was low in the area of the calf (55%), high in the femoral area, iliac area and in the area of the inferior vena cava (92-100%). The specificity was in all areas, incl. the calf, relatively high (94-100%). The investigation revealed the disadvantages of RNV--a low reliability in the area of the calf, the impossibility to detect small and parietal thrombi, the inability to assess the "activity and age" of the thrombus, the more difficult interpretation in insufficiency of venous perforators, and advantages of RNV--a great reliability at higher parts of the venous system and after administration of radiopharmaceutical preparations (RF) into peripheral veins, the possibility of simultaneous examination of pulmonary perfusion without further administration of RF, a low failure rate of intravenous administration of RF (less than 2%); RF do not irritate the venous endothelium and therefore thrombosis cannot develop; in case of paravenous escape of RF local inflammations do not develop, the radiation load is low, there is a small probability of allergic reactions, the method is non-invasive, it can be frequently repeated and used for the follow-up of treatment.

[Plasma proteins and other substances in membrane plasmapheresis. Relation to possibilities and limitations of this therapeutic method]. / Sledování plazmatických bílkovin a dalsích látek pri membránové plazmaferéze. Vztah k moznostem a omezením této lécebné metody.

The authors investigated the effectiveness of therapeutic membrane plasmapheresis and its influence on plasma concentrations of 17 proteins, cholesterol, triacylglycerols, urea, creatinine and uric acid. To this end they made 30 operations on monitors A 2008 PF with filters Plasmaflux P 2, where they exchanged one volume of plasma and replaced it with isooncotic albumin. They assessed the plasma concentrations of the investigated substances before, in the course of and after the operation, estimated sieving coefficients during the 15th and 90th minute and the clearance. Under conditions in vivo they confirmed that the sieving coefficients of the investigated substances approach the value of "1" and the clearance of the filtration rate, i.e. that the investigated substances pass easily through the plasmafilter and that plasmapheresis removes the substances non-selectively. They demonstrated that the assessment of plasma concentrations alone can lead to underestimation of the effectiveness of the operation. Assessment of sieving coefficients and clearance makes more adequate evaluation of the effectiveness of the procedure possible. Assessment of sieving coefficients and clearance made it obvious that plasma concentrations do not depend only on the amount of substance removed by plasmapheresis but also on other factors which must be investigated. The authors' findings support efforts to introduce methods for the selective removal of pathogenetic substances.

[Intensive post-remission therapy of acute myeloid leukemia with high doses of cytosine arabinoside]. / Intenzívní postremisní terapie akutních myeloidních leukémií vysokými dávkami cytosin arabinosidu.

The results are estimated of treatment for acute myeloid leukaemia using intensive post-remission therapy with high doses of cytosine arabinoside (HiDAC). Two women and four men aged 18-34 years were treated with HiDAC. None of them had been given maintenance or boost chemotherapy any more at the time. The patients were rated for the duration of granulocytopenia and thrombocytopenia for the incidence of non-haematological complications and for the duration and quality of survival. The preliminary results are promising and in keeping with those reported by similar clinical centres abroad, namely that maintenance therapy should be phased out in the presence of intensive post-remission treatment.

[Personal experience with implementation of the nationwide program in cardiology in the West Bohemia Region]. / Nase zkusenosti s plnením celospolecenského programu v oblasti kardiologie v Západoceském kraji.

The authors submit experience regarding the implementation of the cardiovascular programme in the West Bohemian region. The implementation of the programme is pretentious as regards staff as well as investments and treatment. In these spheres reasons must be sought why the cardiovascular programme is not always implemented, as required by the authorities and our medical responsibility.

[Initial experience with autologous thrombocytes labeled with 111indium-oxine]. / První zkusenosti s autologními trombocyty znacenými 111indium-oxinem.

The authors elaborated their own modification of the separation and labelling of autologous thrombocytes by means of 111indium-oxine which can be implemented in Czechoslovak departments of nuclear medicine with standard equipment. A total of 123 separations and labellings were made and 85 administrations to patients. The effectiveness of labelling by the described method was 79.5 +/- 6.9%, the separation yield of thrombocytes with regard to complete blood 44.3 +/- 13.8%. The aggregating capacity of the labelled platelets assessed in vitro after ADP stimulation (adenosine diphosphate) was 39.5 +/- 10.1% difference in optic density of platelet rich and platelet poor plasma which is evidence of the preserved viability of thrombocytes. "Recovery" during the 120th minute after administration of normal suspensions was 62.2 +/- 17.9%, the survival time of labelled thrombocytes 8.2 +/- 0.74 days. In patients with idiopathic thrombocytopenic purpura the "recovery" was 49.4 +/- 18%, the survival period 2.9 +/- 1.8 days. In patients after transplantation of the kidney complicated by acute rejection there was an increased accumulation of labelled platelets in the area of the kidney (count rate index 2.32 +/- 0.45). In normally functioning transplanted kidneys the count rate index was 1.42 +/- 0.06. On their own material the authors demonstrate other possibilities of clinical application of scintigraphy by means of labelled autologous platelets (a method hitherto not described in the Ccezhoslovak literature) for the detection of intracardial and arterial thrombosis.

[Frequency of carcinoma in thyroid cysts]. / Frekvence karcinomu v tyroidálních cystách.

The view that cystic thyroid nodes are as a rule benign is disproved by reports from the recent literature which quote an incidence of 17-32% of malignancies in conjunction with thyroid cysts. In 66 patients, investigated by the authors, with thyroid lesions confirmed on biopsy four suffered from thyroid carcinoma (two follicular, one papillary and one solid to anaplastic), i.e. a malignancy in 6%. In the literature it is recommended to follow up on a long-term basis patients with cysts which after thin-needle biopsy do not recede adequately or refill. Biopsies must be repeated, as the cytological yield of biopsies in these instances is not as reliable as in solid nodes. A haemorrhagic appearance of the bioptic specimen and anamnestic data on previous irradiation in the head or neck area are also considered risk factors.