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Biomedical subjects

P Cieslar

Publications and source records attributed to P Cieslar.

At least 19 recordsLinked to original sources
PubMed2006

[High dose therapy with autologous stem cell transplantation in patients with Hodgkin's lymphoma: long-term follow-up in patients treated in one center].

BACKGROUND: Majority of patients with Hodgkin's Lymphoma (HL) can be cured by first line therapy. The high dose therapy (HDT) with autologous stem cell transplantation (ASCT) is the option which can be used in the situation when the conventional therapy failed. METHODS AND RESULTS. Beginning 1994 till 2005 84 pts with HL who did not respond the conventional chemotherapy underwent 105 HDT procedures with ASCT. The median age at the time of HDT was 30.5 years. The reason for salvage therapy followed by HDT with ASCT was the failure to achieve 1st complete remission-- CR (n 16) or the subsequent relapse or progression (n 68). The disease status at the time of HDT after conventional salvage chemotherapy was assessed as chemosensitive in 65 pts (77.4%) and chemoresistant in 19 pts (22.6%). The most frequent HDT regimen used was BEAM (82 HDT), 22 pts entered into the tandem HDT program. Bone marrow only was used as the source of progenitor cells in 4 ASCT, peripheral blood progenitor cells (PBPC) only were used in 85 ASCT and the combination of both in 16 ASCT. The disease status after the HDT with ASCT was assessed (77 pts were qualifiable) as CR in 39 pts (50.6%), PR in 31 (40.3%) and as stable disease or progression in 7 pts (9.1%). Treatment related mortality in HDT with PBPC was 3.9%. The median follow up is 5.3 years. The five year probability of event free survival (EFS) is 43.1% and overall survival 53.2%. The EFS and OS probability respectively for the chemosensitive patients was 48.6% and 62.9% respectively. The status at HDT and the results after it have prognostic significance. There were observed 39 deaths and 26 of them were caused by disease progression. Secondary tumor was observed in 5 pts and in all of them it caused the death. CONCLUSIONS: The HDT with ASCT allows the long-term survival without disease progression in about a half of the patients with reasonable toxicity.

Adult↗
PubMed2003

Image analysis of blood platelets adhesion.

Adhesion of blood platelets is one of the major events in haemostatic and thrombotic processes. We studied adhesion of blood platelets on fibrinogen and fibrin dimer sorbed on solid support material (glass, polystyrene). Adhesion was carried on under static and dynamic conditions and measured as percentage of the surface covered with platelets. Within a range of platelet counts in normal and in thrombocytopenic blood we observed a very significant decrease in platelet adhesion on fibrin dimer with bounded active thrombin with decreasing platelet count. Our results show the imperative use of platelet poor blood preparations as control samples in experiments with thrombocytopenic blood. Experiments carried on adhesive surfaces sorbed on polystyrene showed lower relative inaccuracy than on glass. Markedly different behaviour of platelets adhered on the same adhesive surface, which differed only in support material (glass or polystyrene) suggest that adhesion and mainly spreading of platelets depends on physical quality of the surface. While on polystyrene there were no significant differences between fibrin dimer and fibrinogen, adhesion measured on glass support material markedly differed between fibrin dimer and fibrinogen. We compared two methods of thresholding in image analysis of adhered platelets. Results obtained by image analysis of spreaded platelets showed higher relative inaccuracy than results obtained by image analysis of platelets centres and aggregates.

Blood Platelets↗
PubMed2000

[Prognostic factors and markers of activity in multiple myeloma (results of the Cooperative Group for Diagnosis and Treatment of Multiple Myeloma)].

BACKGROUND: Multiple myeloma (MM) is mostly fatal neoplastic disorder, however, the median survival of 30-40 months does not adequately express the wide spectrum courses of the disease. Therefore better prognostic factors are needed. METHODS AND RESULTS: We analyzed the value of both standard clinical features and cytokines for differential diagnosis, assessment of myeloma activity, prediction of overall survival and duration of remission in a group of 124 patients with MM and in 156 with various monoclonal gammapathies, respectively. The initial levels of Ca2+, LD, Hb, albumin, IL-6, PO4- and creatinine were useful for differentiation of monoclonal gammapathy of undetermined significance from MM. Serum IL-6 correlated with the stage and activity of MM, sIL-6R levels were significantly higher only in stage III and in newly diagnosed myeloma. We did not found the correlation between IL-6 and CRP levels. The usefulness of some standard features for prediction of survival was confirmed (Ca2+, Hb, clinical stage and subclassification A/B according to Durie-Salmon, SB2M > 4 mg/ml, creatinine, LD, ALP) as well as sIL-6R serum level determined both at time of diagnosis and during the course of disease. The prognosis of patients with reversible renal failure and those with intact renal function was not significantly different. Among other features, only serum sIL-6R, measured at time of diagnosis or during the course of disease, had significant predictive value for the assessment of duration of event-free survival in patients with MM. CONCLUSION: Due to short follow-up possible association of high levels of IFN-gamma with better prognosis of MM could not be stated.

Adult↗
PubMed1999

[Monitoring markers of bone turnover in multiple myeloma].

PURPOSE: To assess the efficacy of bone turnover markers monitoring for prediction of overall survival and event-free survival in patients with multiple myeloma. To determine the value of initial measurement for differential diagnosis and evaluation of myeloma stage and activity. METHODS AND RESULTS: We evaluated 79 consecutive, previously untreated patients with myeloma and 24 with monoclonal gammopathy of undetermined significance. Urine excretion rates of pyridinoline (PYR) and deoxypyridinoline (DPYR) as markers of bone resorption and serum osteocalcin (OC) as marker of bone formation were measured at diagnosis and further repeatedly during the course of disease. High-performance liquid chromatography (HPLC) was used to measure urinary excretion rates of PYR and DPYR, serum OC levels was analysed using RIA method. Significant correlation was found between PYR and DPYR levels (p < 0.001) and between DPYR and OC (p < 0.05). Significantly higher urine PYR and DPYR (p < 0.001 and p < 0.01, respectively), but not serum OC, were found in myeloma comparing MGUS. In patients with MM PYR and DPYR levels were significantly higher in stage III vs. I and II (p < 0.01), the correlation with disease activity was not found. The grade of bone involvement according to RTG (osteolysis, osteoporosis, absence of bone lesions) was not reliable as a prognostic factor in our study. Univariate overall survival analysis showed prognostic significance for initial PYR (p < 0.05) but not for DPYR and/or OC. Rapid decrease of PYR (after 1 month of chemotherapy) was associated with the shortest median survival (608 days), however, significant difference was observed only comparing the patients in which PYR decreased 12 months after start of chemotherapy. In the univariate analysis increase of DPYR was the only variable significant for event-free survival (p < 0.05), increase of PYR tend to be significant (p < 0.1). CONCLUSIONS: We confirmed possible contribution of pyridinium cross-links for differential diagnosis of MM and MGUS and the correlation with advanced stage of MM. Initial measurement of PYR and monitoring of both PYR and DPYR during the course of myeloma could be helpful for prediction of overall survival and event-free survival. According to our experience OC is not useful for diagnosis, assessment of disease stage and activity and prediction of survival of patients with MM.

Adult↗
PubMed1998

[Progression of multiple myeloma during treatment with recombinant G-CSF and absence of G-CSF and IL-6 cell surface receptors on malignant cells].

Recombinant human hematopoietic growth factors are widely used in the treatment of multiple myeloma (MM) especially due to the increasing role of autologous blood stem cell transplantation (ABSCT). We report a patient with MM in whom rapid extramedullary progression of disease was observed during stem cell mobilization with G-CSF. In 56-year-old man with relapsing IgG lambda MM myeloablative therapy with ABSCT was planned 2 years after diagnosis. G-CSF is increasing doses was used for mobilization. Ten days after the start of G-CSF therapy 2 extramedullary (subcutaneous) myeloma infiltrates appeared. For the second mobilization high dose cyclophosphamide and VP-16 with subsequent G-CSF was used. During the time of chemotherapy tumour infiltrates disappeared, however, after one week of G-CSF treatment rapid progression of disease with the formation of multiple extramedullary infiltrates occurred and the patient died in June 1996. Small pieces of subcutaneous tumour infiltrates were removed at autopsy and immediately frozen in liquid nitrogen. Using the panel of specific antibodies the expression of cytokine receptors (IL-1, 2, 3, 6, 7, 8, 10, SCF, gp130, G-CSF, GM-CSF, EPO) and Fas, Pgp and 24-34 kD multidrug resistance-associated protein were examined. However, no expression of cytokine receptors on tumor cells was found. On the contrary, high positivity of surface MDR associated proteins was observed.

Disease Progression↗
PubMed1998

[Interleukin-6, tumor necrosis factor alpha and their soluble receptors in Bence-Jones nephropathy. Possible role in pathogenesis andthe importance in the determination of prognosis in renal insufficiency].

BACKGROUND: Bence-Jones nephropathy, the most serious form of which is renal failure, is one of the frequent complications in multiple myeloma (MM). Precise pathogenetic mechanism of renal injury remains unclear. Experimental study points to the possible role of some cytokines in the development of this type of nephropathy. We have investigated the levels of interleukin-6 (IL-6), tumour nekrosis factor alpha (TNF-alpha) and their soluble receptors in patients with plasmocytoma. METHODS AND RESULTS: The group comprised 49 patients with plasmocytoma, mostly with MM. Significantly higher levels of IL-6 were found in patients with irreversible renal insufficiency and/or failure (group A-median 13.3 pg/ml, range 3.6-33.3) comparing patients with reversible impairment (group B-median 3.1-range 1.8-38.4) (p < 0.01) and those with normal renal functions (group C-median 2.3-range 0.97-7.41) (p < 0.01). Significant difference was also found between the groups B and C (p < 0.05). Analysis of variance with the use of various factors showed that the correlation between IL-6 and prognosis of renal disease was stronger (p < 0.001) than the correlation between cytokine levels and the clinical phase of MM (p < 0.05). The difference of IL-6 levels between various clinical stages of MM was not significant. The levels of sIL-6R were significantly increased in patients with both reversible and irreversible renal insufficiency comparing the group with unaffected renal functions (p < 0.05 and p < 0.01 respectively). TNF-alpha levels did not differ between all 3 groups of patients, however, significantly increased values of sTNF-R II were observed in group A vs B and group B vs C (p < 0.05). CONCLUSIONS: We conclude, that some cytokines, especially IL-6/sIL-6R, could play an important role in development of renal insufficiency in MM or other monoclonal gammapathies. We suggest that IL-6 levels could be predictive factor for renal insufficiency recovery.

Bence Jones Protein↗
PubMed1997

[The Bernard-Soulier syndrome. A hereditary functional and structural disorder of blood platelets].

BACKGROUND: The authors submit a clinical and laboratory description of a patient with Bernard-Soulier syndrome diagnosed in this country for the first time. The investigation comprises an analysis of haemostatic functions, selected structural indicators and the detailed morphology of thrombocytes. The analysis of defined inborn functional disorders of thrombocytes is a method for studying haemostatic mechanisms. METHODS AND RESULTS: In addition to standard haemostatic methods flow cytometry in used to assess the size of platelets, and using monoclonal antibodies against glycoproteins, their presence on the surface membrane is assessed. Thrombocytic glycoproteins are further analyzed using diagonal electrophoresis on sodium dodecyl sulphate polyacrylamide gel (SDS-PAGE). The authors found medium thrombocytopaenia with the presence of giant thrombocytes which on elecronmicroscopic examination, with the occasional exception of endoplasmic membrane proliferation, do not display structural deviations. The assessed deviation of thrombocyte aggregation after ristocetin, suggesting a defect of the adhesive capacity of thrombocytes, is apparently due to reduction of the surface glycoprotein GPIb, proved by flow cytometry and SDS-PAGE. The drop of glycoprotein GPIb to 20% of normal values suggests a heterozygote type of disorder with a medium grade of haemorrhagic manifestations. CONCLUSIONS: This is the first case of Bernard-Soulier syndrome in the Czech literature. Its analysis provides evidence of the relationship of the adhesive function to the surface glycoprotein GPIb and confirm the effectiveness of the elaborated diagnostic methods.

Aged↗
PubMed1997

[Effect of clodronate in patients with multiple myeloma. Evaluation of specific markers of bone resorption].

BACKGROUND: In adjuvant therapy of patients with multiple myeloma among others anti-absorption properties of bisphosphonates are used. The objective of the present investigation was to evaluate the effect of long-term oral treatment route clodronate on the bone metabolism in this condition. As markers of bone reabsorption, assessment of pyridinoline and deoxypyridinoline in urine was used. METHODS AND RESULTS: We investigated in an open clinical trial 22 patients with multiple myeloma with bone changes confirmed on X-ray who had a normal calcium and creatinine serum concentration: the control group (A) comprised 13 patients (mean age 59 years, range 38-74 years), the experimental group (B) 9 patients (mean age 54 years, range 42-60 years). The patients in both groups were treated by chemotherapy, to group B concurrently clodronate 3 x 800 mg was administered by the oral route. No statistically significant differences were found between the two groups during the mean follow up period after assessment of the diagnosis (27 vs. 40 months) nor in the clinical stage of the disease. After intervals of 0, 3 and 12 months the excretion of pyridinoline and deoxypyridinoline in urine was assessed by liquid chromatography. At the same time also other parameters of osteoresorption were assessed (urinary calcium and hydroxyproline excretion). At the onset of the investigation the pyridinoline and deoxypyridinoline excretion in groups A and B did not differ statistically (pyr; 120.63 +/- 23.76 vs. 136.23 +/- 22.13 mumol/mmol creatinine. d-pyr: 19.61 +/- 3.65 vs. 22.76 +/- 5.40 mumol/mmol creatinine). After three months in group B a statistically significant drop of excretion of both metabolites was recorded (pyr. to 84.11 +/- 38.67 mumol/mmol creatinine, d-pyr. to 15.23 +/- 6.10 mumol/mmol creatinine). Their significantly reduced excretion persisted also after one year (pyr. 85.52 +/- 60.96 mumol/mmol creatinine, d-pyr. 12.6 +/- 6.56 mumol/mmol creatinine). CONCLUSIONS: Using specific markers, pyridinoline and deoxypyridinoline, the authors proved the favourable effect of long-term administration of clodronate on the bone metabolism in patients with multiple myeloma.

Adult↗
PubMed1996

[Renal involvement in monoclonal gammopathies].

Renal affections are a frequent and clinically important complication of monoclonal gammapathies (MG), in particular of multiple myeloma (MM). The main pathogenetic factor in its development is most probably, despite the participation of other nephrotoxic factors, the action of Bence-Jones protein on the renal parenchyma. Mechanisms of renal affection differ - paraprotein (pp) interferes with tubular functions, precipitates in the cells of the tubular epithelium or in the tubular lumen, is deposited in renal tissue in the form of deposits. The main clinical manifestations include proteinuria, impaired tubular functions and reduced filtration capacity of the kidneys. In 5-10% patients renal failure develops, formerly associated with the unequivocally adverse prognosis of the disease. The change of the therapeutic approach which combines haematological and symptomatic treatment, incl. methods of extracorporeal treatment of the blood, however leads in half the patients to improvement or complete restitution of renal functions. The development of the disease is therefore to a considerable extent determined by the activity of the basic disease and its response to chemotherapy.

Humans↗
PubMed1996

[Disorders of anticoagulation and fibrinolysis in monoclonal gammopathies--another mechanism of paraprotein interference with hemostasis].

We have investigated the possible interaction of paraprotein (pp) with anticoagulation mechanisms and fibrinolysis. Eighty four patients with monoclonal gammapathy (MG) were included to the study, 59 of them with multiple myeloma (MM). In 48.8% cases some defect was found. Decreased levels of antithrombin III (AT III) was observed in 13.3%, protein C (PC) in 18.3% and protein S (PS) in 13.5% of patients. Distribution between the free and the bound PS fraction remained normal. The most frequent abnormality found was the reduction of plasminogen (PLG) activity, which was observed in 35.1% and elevated levels of plasminogen activator inhibitor, detected in 42.3% of cases, respectively. Decreased plasminogen activator activity was observed in only one patient. The relationship between isotype and concentration of paraprotein and frequency of factor levels abnormalities was not found. The incidence of arterial and/or venous thrombosis was higher in patients with laboratory defect in comparison with the unaffected, however, the difference was not statistically significant. In contrast, the incidence of hemorrhagic complications was significantly lower in these patients (p < 0.01), although in most of them simultaneous defect of plasmatic coagulation and/or platelet functions was detected. We suggest, the interaction with both hemostatic and anticoagulation systems could result to "elimination" of inauspicious effect of pp on hemostasis. The impairment of anticoagulation systems and fibrinolysis is another type of paraprotein interference with hemostasis. It is also considered to be another pathogenetic mechanism of secondary deficiency of AT III, PC, PS and PLG.

Adult↗
PubMed1995

[Renal impairment in monoclonal gammapathies. Clinical study].

BACKGROUND: Renal involvement is an important and frequent complication in patient with monoclonal gammapathy (MG), especially in multiple myeloma (MM). Light chain proteinuria produces many renal manifestations, the most serious form is acute renal failure, which occurs in 5-10% of patients with MM. The frequency and form of renal involvement was determined in a group of patients with MG. The disturbances observed were correlated with the concentration and type of paraprotein in serum and urine. METHODS AND RESULTS: We investigated 82 patients, 37 men and 45 women with an average age of 63.5 years. Apart from standard nephrologic tests the aminoaciduria/24 h and urine acidification capacity was determined. In some patients renal biopsy was performed. Proteinuria was observed in 66 cases (80.5%), in 54 of them of Bence-Jones type. Nephrotic syndrome developed in 4 patients, in all cases the renal amyloidosis was present. Renal insufficiency was diagnosed in 39 patients (47.5%), mostly in MM. In 14 cases was renal insufficiency reversible, in 14 remain stable and in 11 progressed during the course of disease. Irreversible progression developed in terminal phase of disease in most cases. Acute renal failure was observed in 6 patients, only in four of them further course of renal disease could be evaluated. In half of these 4 patients the renal failure was reversible. CONCLUSIONS: Higher frequency of proteinuria and renal insufficiency was detected in patients with light chain paraprotein of lambda type, or biclonal kappa+lambda type. Aminoaciduria was diagnosed in 40% of patients, we did not observe complete Fanconi's syndrome. Incompleted form of renal tubular acidosis we diagnosed in 52% of cases without other signs of renal involvement.

Female↗
PubMed1991

[Prognostic factors in non-Hodgkin's malignant lymphoma].

A group of 271 patients with non-Hodgkin's malignant lymphomas from years 1975-1989 was tested using multivariant statistical analysis, from the point of view of the prognostic value their basic clinical and laboratory data. In the group of low grade malignancy lymphomas, the following factors showed a prognostic validity: clinical stage, general status, centrocytic histological subtype, and anaemia. In the group of high grade malignant lymphomas following one were set as prognostically important: general status, clinical stage and age. In particular histological subtypes of low grade malignancy statistically valid difference of survival was not proved, the centrocytic type excluded. However, the difference was found between these types and particular subtypes of high malignancy grade. Based on these results, the Cox's risk model was made, enabling us to define 4 risk groups according to the histological subtype and clinical stage: group A (risk less than 0.5), group B (risk = 0.5-1.0), group C (risk = 1.0-2.0), group D (risk greater than 2.0).

Female↗
PubMed1991

[Hemostasis disorders in monoclonal gammopathies].

The authors investigated haemostatic parameters of 43 patients with monoclonal gammapathy with principal diagnosis of multiple myeloma (MM-35), non-Hodgkin's lymphoma (NHL-3), M. Waldenström (3) and monoclonal gammapathy of undetermined significance (MGUS-2). Primary haemostasis defect was found in 24 patients. With the exception of 2 thrombocytopenic patients, the defect of aggregation, procoagulant activity and retraction is supposed to be caused by paraprotein. The examination of the 14C 5-HT release and TX B2 synthesis in thrombocytes showed, that platelet activation is unaffected and the paraprotein interferes with interactions of thrombocytes or with coagulation system. In plasma coagulation system explicit abnormalities were found only in thrombin time in 12 patients. The more detailed examination disclosed, that the defect resulted from paraprotein interference with fibrin monomer polymerisation. The thrombin proteolytic activity remained unaffected. In 3 patients shortened euglobulin lysis time was observed. Laboratory haemostasis defect was found in 26 patients (60%), however, the bleeding symptoms manifested in 5 cases (11%) only. The analysis of study results showed, that the most important abnormalities leading to overt bleeding are thrombocytopenia or combined haemostasis defect. Isolated laboratory defects remained silent in most cases.

Female↗
PubMed1990

Subclinical course of cholesterol ester storage disease (CESD) diagnosed in adulthood. Report on two cases with remarks on the nature of the liver storage process.

An extremely benign variant of cholesterol ester storage disease (CESD) was diagnosed in two female patients aged 43 and 56 years. In one of them the course was entirely subclinical until a stroke at the age of 47, most probably a complication of secondary hyperlipoproteinaemia. The diagnosis was made accidentally in vivo during extensive examination for concomitant monoclonal gammapathy. The other patient (aged 56), still displays a fairly stable course with minor dyspeptic symptoms. The clinical findings in both patients were confined to moderate well tolerated hepatomegaly, hyperlipoproteinaemia of IIb type and xanthelasmata. Acid lipase activity was markedly deficient in peripheral leukocytes and cultured fibroblasts. These cases represent a rare adult variant the existence of which should be borne in mind in the differential diagnosis of chronic liver disease in advanced age and of hyperlipoproteinaemic states. The diagnostic criteria for the routine clinicopathological steps are summarized with emphasis on a special lipopigment deposition pattern, encompassing inhibition and modification of lipofuscin generation in hepatocytes and an excess of ceroid production in both portal and intralobular histiocytes. The varied ultrastructural appearance of the lysosomal limiting membrane complex is described.

Acetylesterase↗
PubMed1990

[Glanzmann thrombasthenia--a defect in the surface membrane of platelets].

The authors present a clinical description, detailed platelet function analysis, and certain biochemical parameters in two siblings with Glanzmann thrombasthenia (G. t.). The isolated occurrence of this disorder in the family corresponds with its autosomal recessive inheritance. In both cases blood platelets completely failed to aggregate. In contrast, the platelet interaction with ristocetin, reflecting their ability to adhere to the subendothelium, the so-called "shape change", the storage granule contents and their release and arachidonic acid metabolism were unaffected. Further, the aggregation abnormality was accompanied by marked procoagulant activity and clot retraction defects; these functions, similarly as aggregation, are implemented on the platelet surface. The analysis of blood platelet proteins, using two dimensional polyacrylamide electrophoresis, confirmed the absence of glycoprotein GP IIb and IIIa and a decrease of the fibrinogen content. The analysis of these findings in G. t. led to the contemporary concept that GP IIb and IIIa on the platelet surface act as receptors for platelet aggregation.

Adult↗
PubMed1989

[Treatment of chronic proliferative glomerulonephritis using acetylsalicylic acid and dipyridamole].

Fourteen patients with chronic proliferative glomerulonephritis were given for the period of one year 400 mg acetylsalicylic acid and 225 mg dipyridamole per day. During this treatment the thrombocyte aggregation became normal, however, the mean reduction of antiheparin plasma activity was not statistically significant. Normal synthesis of renal prostacyclin declined significantly as a result of treatment, while the renal thromboxane A2 synthesis remained normal even during treatment. Treatment did not influence proteinuria. The mean annual decline of glomerular filtration was greater during the investigation period than the mean annual decline in previous years, the difference was, however, only at the borderline of statistical significance. The authors did not prove a favourable effect of this treatment in patients with chronic proliferative glomerulonephritis.

Adult↗
PubMed1989

[Holter monitoring of patients treated with cytostatic agents].

After cytostatic treatment severe arrhythmias, the development of angina pectoris and even the development of acute myocardial infarction and sudden death were observed. Therefore we made in 42 patients with malignant haematological disease treated with cytostatics 96 Holter monitorings of the electrocardiographic signal. The monitoring was made during the administration of cytostatics as well as during the time interval between the administration of combinations of cytostatics. In both instances (during the administration and during the interval between administration) we recorded a surprisingly high, mean all-day as well as maximal, heart rate. In the group monitored during administration of chemotherapeutic drugs we observed 5-8 hours after administration of cytostatics serious ventricular arrhythmias [incl. ventricular tachycardia], denivelization of the ST segment, paroxysms of supraventricular tachycardia. In the group monitored during the interval between administration of cytostatics the sick-sinus syndrome was recorded, as well as a passive nodal rhythm, disorders of the intraventricular conduction. The described changes are explained by the release of vasoactive substances after administration of cytostatics, by a change of the transmembrane calcium transport leading to an increased excitability of the heart muscle and possibly to coronary spasms and direct irreversible damage of the conduction system.

Adult↗