The authors describe a rare case of systemic mastocytosis without skin infiltration. The first sy... more The authors describe a rare case of systemic mastocytosis without skin infiltration. The first symptom were episodes of flushing in the face and upper trunk. From the case-history it was assumed that the condition had a several year's benign course, the diagnosis was established in the stage of malignant acceleration of the disease from bone marrow biopsy and liver biopsy. Atypical mastocytes displayed metachromasia with toluidine blue and positive naphthol-AS-D chloroacetate esterase. Symptomatic treatment with sodium cromoglycate reduced temporarily the frequency of flushing episodes, but it was not possible to arrest the increase of the mastocyte mass by cytostatic treatment.
Anticoagulant treatment with coumarins is due to it unequivocal benefit and relatively low risk i... more Anticoagulant treatment with coumarins is due to it unequivocal benefit and relatively low risk increasingly used for prevention of sudden cerebrovascular attacks, in atrial fibrillation, in the treatment of thromboembolic disease, as part of treatment after replacement of cardiac valves and other diseases. With the increasing number of indications and patients treated with oral anticoagulants the number of haemorrhagic complications is increasing. The submitted case-history demonstrates an uncommon haemorrhagic complication, retroperitoneal haematoma associated with a neurological symptomatology in a 59-year-old patient who had prolonged anticoagulant treatment with monocoumarin with permanent non-rheumatic atrial fibrillation, a history of an anteroseptal myocardial infarction with an aneurysm and apical thrombus, polycythemia and chronic venous insufficiency. In addition to anamnestic data and the clinical picture the final establishment of the diagnosis was significantly assiste...
The authors examined the thrombocyte aggregation in 10 controls and 17 patients with the diagnosi... more The authors examined the thrombocyte aggregation in 10 controls and 17 patients with the diagnosis of primary hypothyroidism before and after 2 months substitution treatment with levothyroxine. They recorded a significantly reduced intensity of the aggregation response in untreated patients as compared with controls after adrenaline (p < 0.01), ADP (p < 0.01) but not after ristocetin. Impaired thrombocyte aggregation was observed in 11 of 17 patients, i.e. in 65%. After treatment the thrombocytopathy improved in 7 of 11 patients (63%), in four it persisted. Except one female patient the thrombocytopathy improved in all patients with manifest hypothyroidism. In patients with the latent form of hypothyroidism probably an independent coincidence of elevated TSH levels and impaired thrombocyte function was involved. The authors did not detect any cases of acquired von Willebrand's disease. In the conclusion the authors mention that impaired thrombocyte aggregation is a frequen...
The authors describe Loeffler's endocarditis and the treatment of this clinical entity. Among... more The authors describe Loeffler's endocarditis and the treatment of this clinical entity. Among diagnostic methods which drew attention to a cardiac affection associated with eosinophilia, non-invasive examination methods were of decisive importance. They comprised conventional electrocardiographic examination, X-ray of the chest and two-dimensional echocardiography.
The levels of some cardiovascular risk factors (lipids, apolipoproteins and fibrinogen) were meas... more The levels of some cardiovascular risk factors (lipids, apolipoproteins and fibrinogen) were measured in groups of Type-2 diabetic patients with lower limb proximal (ileofemoral) and distal (trifurcational) artery macroangiopathy, diagnosed by Doppler ultrasound, and in a group of diabetics without macroangiopathy. The highest mean levels of total and LDL-cholesterol, apolipoprotein B and triacylglycerols were observed in patients with proximal vessel involvement. Significant correlations were found between the thigh/arm index and total cholesterol, LDL-cholesterol, apolipoprotein B and stroke prevalence. On the other hand, a significant correlation was found between ankle/thigh index and fibrinogen. The results of the study suggest that different pathogenetic mechanisms may play a role in the development of ileofemoral and trifurcational vessel disease.
Some hematologic parameters have been measured in 80 patients with Type 2 diabetes mellitus. The ... more Some hematologic parameters have been measured in 80 patients with Type 2 diabetes mellitus. The patients were divided into three groups: (a) proximal (pelvic and femoral) lower limb macroangiopathy; (b) distal (tibial) macroangiopathy; and (c) control group of diabetics without lower limb macroangiopathy. Mean hemoglobin, hematocrit and fibrinogen values were significantly higher in both the proximal and distal macroangiopathy groups in comparison with the controls. On the other hand, mean leucocyte and platelet counts were significantly elevated only in the proximal macroangiopathy group. Significant correlations were observed in univariate and multivariate analyses between blood fibrinogen concentration and pressure indices expressing severity of lower limb macroangiopathy (ankle/thigh, ankle/arm). In summary, increased levels of hematologic parameters contributing to the increase of whole blood viscosity were observed in Type 2 diabetics with arteriosclerosis obliterans. The obs...
An episode of gastroenteritis triggered severe necrosis of all extremities in a previously asympt... more An episode of gastroenteritis triggered severe necrosis of all extremities in a previously asymptomatic male. Hepatic and renal involvement were also manifest, while the hematological picture was one of thrombotic microangiopathic hemolytic anemia. Antiphospholipid antibodies were negative. He responded well to a combination of plasma exchange, anticoagulation (heparin), parenteral steroids, and antibiotics, as well as vasodilators (prostacycline) and hyperbaric oxygen, but died because of a cerebral hemorrhage. The differential diagnosis included thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome, or seronegative catastrophic antiphospholipid (Asherson's) syndrome. The dangers of administering such a combination of therapies with anticoagulation, as well as vasodilatation (prostacycline) and hyperbaric oxygen, are highlighted by the case report and emphasized.
An episode of gastroenteritis triggered severe necrosis of all extremities in a previously asympt... more An episode of gastroenteritis triggered severe necrosis of all extremities in a previously asymptomatic male. Hepatic and renal involvement were also manifest, while the hematological picture was one of thrombotic microangiopathic hemolytic anemia. Antiphospholipid antibodies were negative. He responded well to a combination of plasma exchange, anticoagulation (heparin), parenteral steroids, and antibiotics, as well as vasodilators (prostacycline) and hyperbaric oxygen, but died because of a cerebral hemorrhage. The differential diagnosis included thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome, or seronegative catastrophic antiphospholipid (Asherson's) syndrome. The dangers of administering such a combination of therapies with anticoagulation, as well as vasodilatation (prostacycline) and hyperbaric oxygen, are highlighted by the case report and emphasized.
Rozhledy v chirurgii : měsíčník Československé chirurgické společnosti, 1997
The authors describe the case-history of an 18-year-old patient with an extensive venous mesenter... more The authors describe the case-history of an 18-year-old patient with an extensive venous mesenteric thrombosis. The case proved fatal despite repeated surgery as a result of relapsing gangrene of the small intestine with diffuse stercoral peritonitis. Thrombosis of the mesenteric veins is a rare disease and accounts only for 4 to 10% of all acute intestinal episodes. The cause of the disease is either idiopathic but more frequently it is associated with various types of coagulopathy. In this context the authors discuss etiological factors, symptoms, diagnosis as well as possible treatment of acute mesenteric venous thrombosis.
Recombinant human erythropoietin is widely used to treat anemia associated with cancer and with t... more Recombinant human erythropoietin is widely used to treat anemia associated with cancer and with the myelosuppressive effects of chemotherapy, particularly platinumbased regimens. Erythropoietin is the principal regulator of erythroid cell proliferation, differentiation, and apoptosis. Recently, the antiapoptotic and proliferative effects of erythropoietin on nonhematopoietic cells were also established. We now show the effect of erythropoietin treatment on the response of A2780 and SKOV3 ovarian carcinoma cell lines to photodynamic therapy (PDT) using hypericin. SKOV3 exhibited an increased resistance to hypericin when cells were treated with erythropoietin. This resistance was reversed by treatment of SKOV3 cells with the specific Janus kinase 2 kinase inhibitor AG490 or the tyrosine kinase inhibitor genistein. These results support a role for the specific erythropoietin-induced Janus kinase 2/STAT signal transduction pathway in PDT resistance. Evidence of erythropoietin signaling was obtained by the demonstration of Akt phosphorylation in both A2780 and SKOV3 cells. Erythropoietin-treated SKOV3 cells exhibited decreased apoptosis induced by hypericin, an effect that was blocked by the phosphoinositide 3-kinase/Akt inhibitor wortmannin. These results may have important implications for ovarian cancer patients undergoing PDT and receiving erythropoietin. [Mol Cancer Ther
Background: Inherited disorders of fibrinogen are rare and affect either the quantity (hypofibrin... more Background: Inherited disorders of fibrinogen are rare and affect either the quantity (hypofibrinogenaemia and afibrinogenaemia) or the quality of the circulating fibrinogen (dysfibrinogenaemia). Extensive allelic heterogeneity has been found for all three disorders: in congenital afibrinogenaemia .30 mutations, the majority in FGA, have been identified in homozygosity or in compound heterozygosity. Several mutations have also been identified in patients with hypofibrinogenaemia; many of these are heterozygous carriers of afibrinogenaemia null mutations. Objective: To report the case of a patient from Slovakia diagnosed with hypofibrinogenaemia characterised by fibrinogen concentrations of around 0.7 g/l. Results: The patient was found to be heterozygous for a novel missense mutation W253C (W227C in the mature protein) in the C-terminal globular domain of the fibrinogen c chain. Co-expression of the W253C FGG mutant cDNA (fibrinogen Bratislava) in combination with wild-type FGA and FGB cDNAs showed that fibrinogen molecules containing the mutant c chain can assemble intracellularly but are not secreted into the media, confirming the causative nature of the identified mutation. Conclusions: Current analysis of fibrinogen Bratislava indicates that the domains important for the processes of hexamer assembly and hexamer secretion should not be considered as strictly restricted to one or other fibrinogen chain.
To gain insight into the mitochondrial gene pool diversity of European populations, we studied mi... more To gain insight into the mitochondrial gene pool diversity of European populations, we studied mitochondrial DNA (mtDNA) variability in 207 subjects from western and eastern areas of Slovakia. Sequencing of two hypervariable segments, HVS I and HVS II, in combination with screening of coding region haplogroup-specific RFLP-markers, revealed that the majority of Slovak mtDNAs belong to the common West Eurasian mitochondrial haplogroups (HV, J, T, U, N1, W, and X). However, a few sub-Saharan African (L2a) mtDNAs were detected in a population from eastern part of Slovakia. In addition, about 3% of mtDNAs from eastern Slovakia encompass Roma-specific lineages. By means of complete mtDNA sequencing we demonstrate here that the Roma-specific M-lineages observed in gene pools of different Slavonic populations (Slovaks, Poles and Russians), belong to Indian-specific haplogroups M5a1 and M35. Moreover, we show that haplogroup J lineages found in gene pools of the Roma and some Slavonic populations (Czechs and Slovaks) belong to new subhaplogroup J1a, which is defined by coding region mutation at position 8460.
An episode of gastroenteritis triggered severe necrosis of all extremities in a previously asympt... more An episode of gastroenteritis triggered severe necrosis of all extremities in a previously asymptomatic male. Hepatic and renal involvement were also manifest, while the hematological picture was one of thrombotic microangiopathic hemolytic anemia. Antiphospholipid antibodies were negative. He responded well to a combination of plasma exchange, anticoagulation (heparin), parenteral steroids, and antibiotics, as well as vasodilators (prostacycline) and hyperbaric oxygen,
The authors describe a rare case of systemic mastocytosis without skin infiltration. The first sy... more The authors describe a rare case of systemic mastocytosis without skin infiltration. The first symptom were episodes of flushing in the face and upper trunk. From the case-history it was assumed that the condition had a several year's benign course, the diagnosis was established in the stage of malignant acceleration of the disease from bone marrow biopsy and liver biopsy. Atypical mastocytes displayed metachromasia with toluidine blue and positive naphthol-AS-D chloroacetate esterase. Symptomatic treatment with sodium cromoglycate reduced temporarily the frequency of flushing episodes, but it was not possible to arrest the increase of the mastocyte mass by cytostatic treatment.
Anticoagulant treatment with coumarins is due to it unequivocal benefit and relatively low risk i... more Anticoagulant treatment with coumarins is due to it unequivocal benefit and relatively low risk increasingly used for prevention of sudden cerebrovascular attacks, in atrial fibrillation, in the treatment of thromboembolic disease, as part of treatment after replacement of cardiac valves and other diseases. With the increasing number of indications and patients treated with oral anticoagulants the number of haemorrhagic complications is increasing. The submitted case-history demonstrates an uncommon haemorrhagic complication, retroperitoneal haematoma associated with a neurological symptomatology in a 59-year-old patient who had prolonged anticoagulant treatment with monocoumarin with permanent non-rheumatic atrial fibrillation, a history of an anteroseptal myocardial infarction with an aneurysm and apical thrombus, polycythemia and chronic venous insufficiency. In addition to anamnestic data and the clinical picture the final establishment of the diagnosis was significantly assiste...
The authors examined the thrombocyte aggregation in 10 controls and 17 patients with the diagnosi... more The authors examined the thrombocyte aggregation in 10 controls and 17 patients with the diagnosis of primary hypothyroidism before and after 2 months substitution treatment with levothyroxine. They recorded a significantly reduced intensity of the aggregation response in untreated patients as compared with controls after adrenaline (p < 0.01), ADP (p < 0.01) but not after ristocetin. Impaired thrombocyte aggregation was observed in 11 of 17 patients, i.e. in 65%. After treatment the thrombocytopathy improved in 7 of 11 patients (63%), in four it persisted. Except one female patient the thrombocytopathy improved in all patients with manifest hypothyroidism. In patients with the latent form of hypothyroidism probably an independent coincidence of elevated TSH levels and impaired thrombocyte function was involved. The authors did not detect any cases of acquired von Willebrand's disease. In the conclusion the authors mention that impaired thrombocyte aggregation is a frequen...
The authors describe Loeffler's endocarditis and the treatment of this clinical entity. Among... more The authors describe Loeffler's endocarditis and the treatment of this clinical entity. Among diagnostic methods which drew attention to a cardiac affection associated with eosinophilia, non-invasive examination methods were of decisive importance. They comprised conventional electrocardiographic examination, X-ray of the chest and two-dimensional echocardiography.
The levels of some cardiovascular risk factors (lipids, apolipoproteins and fibrinogen) were meas... more The levels of some cardiovascular risk factors (lipids, apolipoproteins and fibrinogen) were measured in groups of Type-2 diabetic patients with lower limb proximal (ileofemoral) and distal (trifurcational) artery macroangiopathy, diagnosed by Doppler ultrasound, and in a group of diabetics without macroangiopathy. The highest mean levels of total and LDL-cholesterol, apolipoprotein B and triacylglycerols were observed in patients with proximal vessel involvement. Significant correlations were found between the thigh/arm index and total cholesterol, LDL-cholesterol, apolipoprotein B and stroke prevalence. On the other hand, a significant correlation was found between ankle/thigh index and fibrinogen. The results of the study suggest that different pathogenetic mechanisms may play a role in the development of ileofemoral and trifurcational vessel disease.
Some hematologic parameters have been measured in 80 patients with Type 2 diabetes mellitus. The ... more Some hematologic parameters have been measured in 80 patients with Type 2 diabetes mellitus. The patients were divided into three groups: (a) proximal (pelvic and femoral) lower limb macroangiopathy; (b) distal (tibial) macroangiopathy; and (c) control group of diabetics without lower limb macroangiopathy. Mean hemoglobin, hematocrit and fibrinogen values were significantly higher in both the proximal and distal macroangiopathy groups in comparison with the controls. On the other hand, mean leucocyte and platelet counts were significantly elevated only in the proximal macroangiopathy group. Significant correlations were observed in univariate and multivariate analyses between blood fibrinogen concentration and pressure indices expressing severity of lower limb macroangiopathy (ankle/thigh, ankle/arm). In summary, increased levels of hematologic parameters contributing to the increase of whole blood viscosity were observed in Type 2 diabetics with arteriosclerosis obliterans. The obs...
An episode of gastroenteritis triggered severe necrosis of all extremities in a previously asympt... more An episode of gastroenteritis triggered severe necrosis of all extremities in a previously asymptomatic male. Hepatic and renal involvement were also manifest, while the hematological picture was one of thrombotic microangiopathic hemolytic anemia. Antiphospholipid antibodies were negative. He responded well to a combination of plasma exchange, anticoagulation (heparin), parenteral steroids, and antibiotics, as well as vasodilators (prostacycline) and hyperbaric oxygen, but died because of a cerebral hemorrhage. The differential diagnosis included thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome, or seronegative catastrophic antiphospholipid (Asherson's) syndrome. The dangers of administering such a combination of therapies with anticoagulation, as well as vasodilatation (prostacycline) and hyperbaric oxygen, are highlighted by the case report and emphasized.
An episode of gastroenteritis triggered severe necrosis of all extremities in a previously asympt... more An episode of gastroenteritis triggered severe necrosis of all extremities in a previously asymptomatic male. Hepatic and renal involvement were also manifest, while the hematological picture was one of thrombotic microangiopathic hemolytic anemia. Antiphospholipid antibodies were negative. He responded well to a combination of plasma exchange, anticoagulation (heparin), parenteral steroids, and antibiotics, as well as vasodilators (prostacycline) and hyperbaric oxygen, but died because of a cerebral hemorrhage. The differential diagnosis included thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome, or seronegative catastrophic antiphospholipid (Asherson's) syndrome. The dangers of administering such a combination of therapies with anticoagulation, as well as vasodilatation (prostacycline) and hyperbaric oxygen, are highlighted by the case report and emphasized.
Rozhledy v chirurgii : měsíčník Československé chirurgické společnosti, 1997
The authors describe the case-history of an 18-year-old patient with an extensive venous mesenter... more The authors describe the case-history of an 18-year-old patient with an extensive venous mesenteric thrombosis. The case proved fatal despite repeated surgery as a result of relapsing gangrene of the small intestine with diffuse stercoral peritonitis. Thrombosis of the mesenteric veins is a rare disease and accounts only for 4 to 10% of all acute intestinal episodes. The cause of the disease is either idiopathic but more frequently it is associated with various types of coagulopathy. In this context the authors discuss etiological factors, symptoms, diagnosis as well as possible treatment of acute mesenteric venous thrombosis.
Recombinant human erythropoietin is widely used to treat anemia associated with cancer and with t... more Recombinant human erythropoietin is widely used to treat anemia associated with cancer and with the myelosuppressive effects of chemotherapy, particularly platinumbased regimens. Erythropoietin is the principal regulator of erythroid cell proliferation, differentiation, and apoptosis. Recently, the antiapoptotic and proliferative effects of erythropoietin on nonhematopoietic cells were also established. We now show the effect of erythropoietin treatment on the response of A2780 and SKOV3 ovarian carcinoma cell lines to photodynamic therapy (PDT) using hypericin. SKOV3 exhibited an increased resistance to hypericin when cells were treated with erythropoietin. This resistance was reversed by treatment of SKOV3 cells with the specific Janus kinase 2 kinase inhibitor AG490 or the tyrosine kinase inhibitor genistein. These results support a role for the specific erythropoietin-induced Janus kinase 2/STAT signal transduction pathway in PDT resistance. Evidence of erythropoietin signaling was obtained by the demonstration of Akt phosphorylation in both A2780 and SKOV3 cells. Erythropoietin-treated SKOV3 cells exhibited decreased apoptosis induced by hypericin, an effect that was blocked by the phosphoinositide 3-kinase/Akt inhibitor wortmannin. These results may have important implications for ovarian cancer patients undergoing PDT and receiving erythropoietin. [Mol Cancer Ther
Background: Inherited disorders of fibrinogen are rare and affect either the quantity (hypofibrin... more Background: Inherited disorders of fibrinogen are rare and affect either the quantity (hypofibrinogenaemia and afibrinogenaemia) or the quality of the circulating fibrinogen (dysfibrinogenaemia). Extensive allelic heterogeneity has been found for all three disorders: in congenital afibrinogenaemia .30 mutations, the majority in FGA, have been identified in homozygosity or in compound heterozygosity. Several mutations have also been identified in patients with hypofibrinogenaemia; many of these are heterozygous carriers of afibrinogenaemia null mutations. Objective: To report the case of a patient from Slovakia diagnosed with hypofibrinogenaemia characterised by fibrinogen concentrations of around 0.7 g/l. Results: The patient was found to be heterozygous for a novel missense mutation W253C (W227C in the mature protein) in the C-terminal globular domain of the fibrinogen c chain. Co-expression of the W253C FGG mutant cDNA (fibrinogen Bratislava) in combination with wild-type FGA and FGB cDNAs showed that fibrinogen molecules containing the mutant c chain can assemble intracellularly but are not secreted into the media, confirming the causative nature of the identified mutation. Conclusions: Current analysis of fibrinogen Bratislava indicates that the domains important for the processes of hexamer assembly and hexamer secretion should not be considered as strictly restricted to one or other fibrinogen chain.
To gain insight into the mitochondrial gene pool diversity of European populations, we studied mi... more To gain insight into the mitochondrial gene pool diversity of European populations, we studied mitochondrial DNA (mtDNA) variability in 207 subjects from western and eastern areas of Slovakia. Sequencing of two hypervariable segments, HVS I and HVS II, in combination with screening of coding region haplogroup-specific RFLP-markers, revealed that the majority of Slovak mtDNAs belong to the common West Eurasian mitochondrial haplogroups (HV, J, T, U, N1, W, and X). However, a few sub-Saharan African (L2a) mtDNAs were detected in a population from eastern part of Slovakia. In addition, about 3% of mtDNAs from eastern Slovakia encompass Roma-specific lineages. By means of complete mtDNA sequencing we demonstrate here that the Roma-specific M-lineages observed in gene pools of different Slavonic populations (Slovaks, Poles and Russians), belong to Indian-specific haplogroups M5a1 and M35. Moreover, we show that haplogroup J lineages found in gene pools of the Roma and some Slavonic populations (Czechs and Slovaks) belong to new subhaplogroup J1a, which is defined by coding region mutation at position 8460.
An episode of gastroenteritis triggered severe necrosis of all extremities in a previously asympt... more An episode of gastroenteritis triggered severe necrosis of all extremities in a previously asymptomatic male. Hepatic and renal involvement were also manifest, while the hematological picture was one of thrombotic microangiopathic hemolytic anemia. Antiphospholipid antibodies were negative. He responded well to a combination of plasma exchange, anticoagulation (heparin), parenteral steroids, and antibiotics, as well as vasodilators (prostacycline) and hyperbaric oxygen,
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