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Biomedical subjects

Z Rolović

Publications and source records attributed to Z Rolović.

At least 19 recordsLinked to original sources
PubMed2005

[Initial 111In-platelet kinetics: indicator of platelet sequestration/destruction site or quality control of platelet labelling?].

Taking into consideration the existing disagreement in the literature, the aim of this paper was to estimate the value of the initial kinetics of autologous platelets labelled with 111In-oxinate, performed during the first 20 minutes after their intravenous injection. Two hypothesis were tested: 1. Initial 111In-platelet kinetics indicates the platelet sequestration site (in patients with normal mean platelet life span)/destruction site (in patients with shortened mean platelet life span), 2. Initial 111In-platelet kinetics indicates the quality of platelet separation and labelling procedure. We performed initial labelled platelet kinetics in thrombocytopenic patients (in order to test the first hypothesis) as well as in control (healthy) subjects (in order to test the second hypothesis). Thirty-nine persons were investigated: 33 with thrombocytopenia: 25 with shortened mean platelet life span, caused by chronic im mune thrombocytopenic purpura (ITP), eight with normal platelet life span and thrombocytopenia caused by myelodysplastic syndrome (MDS), six healthy, control subjects (C). In all 39 persons platelet blood count on the day of platelet labelling was determined, autologous platelet labelling with 111In-oxinate was performed, general and differential yields of platelet labelling (GYL and DYL), as well as mean labelled platelets life span were determined. Besides that, initial labelled platelets kinetics was performed with initial 111In-platelets accumulation in the liver (IPAL) calculation, as well as the late platelet kinetics for platelet sequestration index and platelet sequestration/destruction site determination. We obtained two types of initial labelled platelets kinetics (not only in the patients with shortened platelet life span, but also in the subjects with normal labelled platelets life span), which differed in the IPAL value and in the ratio of the liver and the heart radioactivity: IPAL < 20% and IPAL>20%. We found statistically significant difference in GYL and DYL between the two groups: IPAL<20% and IPAL > 20%. Both yields were higher in IPAL<20% group. There was no significant difference between the two IPAL groups in the platelet blood count, labelled platelet life span, sequestration index and sequestration site. No correlation could be found between IPAL on one side and platelet blood count, sequestration index, and sequestration site on another. We concluded that initial labelled platelet kinetics could not indicate the platelet sequestration/destructon site (which is accomplished by the late labelled platelets kinetics), but nevertheless, it is very sensitive and useful method of platelet separation and labelling quality control. While in vitro quality control parameters (GYL and DYL) indicate the quality of only one part of this procedure, initial labelled platelet kinetics reflects discrete platelet function disturbance that might happen from the moment of blood sample collection till the labelled platelets intravenous injection.

Adult↗
PubMed2005

[Prediction of the splenectomy efficacy in chronic immune thrombocytopenic purpura].

The aim of this investigation was to estimate the possibility of predicting the splenectomy response in patients with chronic immune thrombocytopenic purpura (ITP). The patients' age, sex, megakaryocytes abundance, platelet blood count, production, life span, sequestration/destruction site were considered as possible predictive factors. Thirty-four ITP patients (23 female and 11 male) aged from five to 83 years were investigated. Platelet blood count ranged from 4 to 106 x 10(9)l (mean value was 43 x 10(9)/l). Megakaryocyte abundance was determined in 19/34 ITP patients. Megakaryocytes were numerous in 11/19, present in 7/19 ITP patients and in one patient low megakaryocyte number was registered. In all 34 ITP patients autologous platelet labelling with 111In-oxinate was performed and labelled platelets were reinjected to the ITP patients. This enabled platelet life span, production, sequestration index and sequestration/destruction site determination. Platelet life span ranged from 0,4-5 days (mean value was 1 day). Mean value for platelet production index was 1,1. Platelet sequestration/destruction site in 16 ITP patients was the spleen, and in two it was the liver. Mixed platelet sequestration/destruction site (the liver and the spleen) was registered in 7 ITP patients, while predominantly splenic sequestration/destruction was present in 9 ITP patients. All 34 ITP patients were later submitted to splenectomy, which is a therapeutic option in ITP. Splenectomy result was favorable in 28/34 ITP patients while it was unfavorable in 6/34 (17,6%). Highly significant correlation was noticed between the splenectomy result and platelet sequestration site (p < 0.01). On the other hand, there was no correlation between the splenectomy result on one side, and patient's age, sex, megakaryocyte abundance, platelet production, life span and blood count on the other. Splenectomy result was favorable in all ITP patients with splenic sequestration/detruction of labelled platelets. It was unfavorable in ITP patients with hepatic sequestration of labelled platelets. In ITP patients with mixed platelet sequestration (hepatic and splenic) there were more unfavorable than favorable splenectomy results. Non-invasive method of platelet labelling and platelet sequestration/ /destruction site determination makes easier the clinicians' and ITP patients' decision for the splenectomy in the case when the spleen is the only sequestration site of the labelled platelets, and against the splenectomy, when exclusively hepatic platelet sequestration/destruction is registered.

Adolescent↗
PubMed2004

Myelofibrosis in primary myelodysplastic syndromes: clinical and biological significance.

In a retrospective study of 236 patients with primary myelodysplastic syndromes (MDS), 130 cases (55.1%) revealed myelofibrosis in bone marrow biopsies. It was observed that fibrosis mostly occurs focally or patchy, and collagen deposits were found very rarely (only four patients). The histopathology of bone marrow biopsies revealed several differences between fibrotic and non-fibrotic MDS: cellularity is significantly higher, dysmegakaryopoiesis is more pronounced, plasmocytes and mast cells are more often increased, and disturbance of marrow topography (particularly of the MK- and G-line) can be found more frequently in MDS with myelofibrosis. Reticulin fibrosis occurred in all subtypes of MDS; however, there was a higher incidence in chronic myelomonocytic leukemia. The frequency of abnormal growth of GM-progenitors was significantly higher in the MDS cases with myelofibrosis, compared to the cases without fibrosis. Clinical data showed significantly higher WBC, more frequent presence of immature granulocytes, and higher percentage of myeloblasts in peripheral blood and bone marrow in MDS with myelofibrosis compared to cases without myelofibrosis. Life expectancy was reduced to 13 mo, compared with 35 mo in MDS without fibrosis (p=0.00055). Time to leukemic transformation was 32 mo in MDS with fibrosis, compared with >56 mo in MDS without fibrosis (p=0.015). Myelofibrosis therefore seems to herald a poor prognosis.

Adult↗
PubMed2002

Biological and clinical significance of clonogenic assays in patients with myelodysplastic syndromes.

Biological and clinical significance of growth pattern of hematopoietic progenitors were investigated in 117 patients with primary myelodysplastic syndromes (MDSs) at referral. Abnormal (i.e., "leukemic" or absent) growth of GM colonies (CFU-GM) and GM clusters was found in 47% of patients with "advanced" MDS (RAEB, RAEB-t, and CMML) and in 15% of "low-risk" (RA/RARS) patients. In vitro erythropoiesis was decreased in most of the patients, with significantly lower number of BFU-E in "advanced" MDS than in RA/RARS patients. Megakaryocyte progenitors (CFU-MK) were very low or absent in almost all the patients, regardless of the FAB type. Significant correlation was demonstrated between the number of BFU-E and hemoglobin concentration and between number of CFU-MK and platelet count. Growth capacity of GM progenitors appears to be in proportion to "myeloproliferative" capacity of the malignant clone. T-cell depletion had no influence on growth capacity of hematopoietic progenitors, nor did colony growth respond in a dose-dependent manner to different concentrations of LCM. Growth capacity of MDS hematopoietic progenitors was independent of Bournemouth score, of the presence and type of cytogenetic abnormality, and of the expression of CD95 and caspase-3 antigens on bone marrow cells. However, in patients with "abnormal" growth of GM progenitors, CD34 antigen expression was significantly higher than in patients with "normal" growth. "Abnormal" GM growth was found to be independently predictive regarding the survival and the risk for AML development. In contrast, the prognostic value of erythroid and megakaryocyte cultures was found to be limited.

Adolescent↗
PubMed2000

Recurrent venous thrombosis in a patient with chronic lymphocytic leukemia and acquired protein S deficiency.

A patient with chronic lymphocytic leukemia and an undetectable plasma level of protein S (PS), associated with recurrent venous thrombosis, is described. The laboratory investigation revealed the concomitant presence of an inhibitor directed to PS and a monoclonal protein in the patient's plasma. After treatment with prednisone and cyclophosphamide both the inhibitor to PS and the monoclonal component disappeared.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Megakaryocytopoiesis in refractory chronic immune thrombocytopenia.

The extent of megakaryocytopoiesis (Mk-poiesis) and clinical outcome are evaluated in 14 patients with severe refractory chronic immune thrombocytopenia (rchr ITP). Three out of 14 patients died due to hemorrhage. The number of bleeding episodes and the number of treatment modalities proved to be both sensitive prognostic survival parameters (p < 0.05). Thirty two corticosteroid responsive chr ITP patients (chr ITPPR), 15 not treated patients (chr ITP(NT)) and 14 healthy volunteers (C) served as a control. There was a significant difference in the platelet count between the study groups (p < 0.05). The number of megakaryocytes and promegakaryoblasts per mm3 of bone marrow were significantly lower in rchr ITP patients (p < 0.05) than in chr ITP(PR) and in chr ITP(NT) group, thus implying an inadequate Mk-poiesis in rITP chr patients. From the data presented here it may be suggested that the inadequate Mk-poiesis is operating in rchr ITP.

Adult↗
PubMed1997

Comparative morphometric study of immunohistochemical versus conventional staining for the evaluation of megakaryocytopoiesis in normal and pathological bone marrow biopsies.

Identification of megakaryocytes by immunohistochemistry may be superior to hematoxylin-eosin (HE) stain method for assessing megakaryocyte size and number in clinical specimens; however, a side-by-side comparison of the two methods has not been reported. In the present study, comparative morphometry using both methods was performed on marrow biopsies of normal individuals, and of patients with myelodysplastic syndrome, chronic myeloid leukemia and immune thrombocytopenia. Morphometric results in the present study showed that precise megakaryocyte size can be calculated in normal and pathologic bone marrow sections by using HE stain if one employs stereological corrections. In contrast, megakaryocyte numbers can be more precisely detected by immunohistochemistry than by HE stain, particularly in myelodysplastic syndrome and chronic myeloid leukemia. Differentiation disturbances and ineffective megakaryocytopoiesis in myelodysplastic syndrome were demonstrated by immunomorphometric analyses.

Adult↗
PubMed1995

In vitro drug sensitivity of leukemic progenitors and P-glycoprotein expression in adult acute myeloid leukemia: correlation with induction treatment outcome.

We have investigated the self-renewal capacity (PE2) and in vitro sensitivity to cytosine-arabinoside (ara-C) and daunorubicine (DNR) of leukemic progenitors (CFU-AML) to determine the significance of these tests for predicting induction treatment outcome in 75 adult acute myeloid leukemia (AML) patients. In addition, in a part of this group of patients (n = 46) we determined the expression of P-glycoprotein (P-gp) immunocytochemically and correlated those results with the therapeutic response. We have evaluated 66 patients who showed the following responses: 28/66 complete remissions (CR), 16/66 resistant leukemias (RL) and 22/66 early deaths (ED). The PE2 value was significantly higher in patients with RL than in patients with CR (p < 0.00375). CFU-AML sensitivity to ara-C and DNR alone was not different between response groups, but the difference in CFU-AML sensitivity to the combination of drugs between patients with CR and RL was not significant, although a trend was noted (p < 0.06). P-gp expression was found in only 1/18 patients who achieved CR but in 9/11 patients with RL and 7/11 patients with ED, which is a highly significant difference (p < 0.0006). We concluded that both PE2 and P-gp expression in AML cells are valuable predictors of therapeutic response in adult AML and should be included in creating the best therapeutic approach to AML patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Decreased plasma proteins, increased total plasma-free amino acids, and disturbed amino acid metabolism in the hereditary severe anemia of the Belgrade laboratory (b/b) rat.

The plasma amino acid pattern has been investigated in severely anemic Belgrade laboratory (b/b) rats. Nonanemic heterozygous (b/+) or normal homozygous (+/+) rats of the same age (six weeks) were used as controls. Decreased plasma proteins, increased total free amino acid, and urea concentrations in plasma associated with increased urea and 3-methylhistidine urinary excretion were found, indicating protein and amino acid metabolic alterations in anemic b/b rats. Plasma alanine, glutamine, tyrosine, and phenylalanine concentrations were increased. The significantly reduced molar ratio between valine+leucine+isoleucine and phenylalanine+tyrosine suggested severe disturbance in the hepatic energy-producing system and derangement of hepatic energy status. Partial or complete reversal of the anemia within 3 days by red blood cell transfusion or within 3 weeks by iron treatment resulted in normalization of tyrosine, alanine, glutamine, and total amino acid concentrations in plasma, as well as of molar ratio between valine+leucine+isoleucine and phenylalanine+tyrosine. This indicated a better oxygen supply to the liver and normalization of the hepatic energy status. These findings suggest that the metabolic disturbances in the b/b rat are the consequence of hypoxia due to the severe anemia.

Alanine↗
PubMed1993

Determining the lifespan of platelets labelled with 111In oxinate--first results.

The paper presents the new method of platelet labelling, quality control of separation and labelling, as well as the investigation of the 111In oxinate labelled platelets lifespan. Among the 23 investigated persons, there were 4 hematologically healthy persons and 19 ITP patients. Homologous and autologous labellings were done in one and 22 persons, respectively. Determination of the platelet lifespan in healthy subjects enabled the estimation of "in vitro" procedures of separation and labelling, as well as "in vivo" behaviour of the labelled platelets. Our results show that 111In oxinate labelled platelets have normal lifespan (8.9 +/- 0.6 days), which means that the procedure of separation and labelling does not damage them. In the ITP patients the platelet lifespan is shortened (0.4-4.6 days), which confirms the mechanism of thrombocytopenia. In the subject where homologous labelling had been done, we found out the existence of sensibilisation toward the donor platelets, which lead to the correction of therapy.

Adolescent↗
PubMed1991

Abnormal megakaryocytopoiesis in the Belgrade laboratory rat.

The Belgrade laboratory (b/b) rat has a hereditary hypochromic microcytic anemia because of defective transmembrane iron transport into erythroblasts. The present study was prompted by our previous work in which we showed that the b/b rat has hypomegakaryocytic thrombocytopenia associated with increased megakaryocyte size. To define the basic mechanism underlying this abnormality in the b/b rat we have studied both megakaryocytopoiesis and granulopoiesis in anemic b/b rats, chronically transfused b/b rats, iron-treated b/b rats, and controls. We have found decreased concentrations of megakaryocyte and granulocyte progenitors in the marrow of b/b rats. Full correction of the severe anemia by chronic transfusion resulted in normalization of megakaryocyte progenitors, small acetylcholinesterase positive cells, megakaryocyte size, and platelet counts, along with granulocyte progenitors. In contrast, the partial correction of anemia obtained by iron treatment resulted in improvement, but not normalization, of these parameters. These findings indicate that abnormal megakaryocytopoiesis in the b/b rat can be best interpreted as a consequence of hypoxia because of the severe anemia. Because we have recently shown that the number of erythroid progenitors in b/b rats is also low, we propose that abnormal megakaryocytopoiesis in this animal is a reflection of an acquired stem cell disorder induced by the prolonged hypoxia resulting from the severe anemia.

Anemia, Hypochromic↗
PubMed1990

Megakaryocytopoiesis in experimentally induced chronic normobaric hypoxia.

It was recently proposed that prolonged hypoxia produces hypomegakaryocytic thrombocytopenia by reducing the pool of committed megakaryocyte progenitor cells at the expense of a greatly expanded erythroid progenitor pool. In order to test this hypothesis we have studied the relationship between megakaryocytopoiesis, erythropoiesis, and granulopoiesis at the level of progenitor cells (megakaryocyte colony-forming unit, CFU-Mk; erythroid CFU, CFU-E; erythroid burst-forming units; BFU-E; and granulocyte-macrophage CFU, CFU-GM) in the marrow of rats exposed for 4 weeks to normobaric hypoxia. We have found that hypomegakaryocytic thrombocytopenia was accompanied by decreased CFU-Mk, increased CFU-E, and a normal number of BFU-E and CFU-GM. These results support the hypothesis that prolonged hypoxia reduces the precursor cell commitment to differentiate into the megakaryocyte series by enhancing demand for differentiation into the erythroid cell line. However, the underlying mechanism needs further investigation.

Animals↗
PubMed1989

Chronic myeloid leukemia associated with pure red cell aplasia and terminating in promyelocytic transformation.

After intermittent treatment with busulphan over a 7-year period for chronic myeloid leukemia (CML) in chronic phase, a 39-year-old female developed leukocytosis in association with pure red cell aplasia (PRCA). Bone marrow examination confirmed erythroid aplasia, and culture revealed a total absence of erythroid progenitor cells. The patient then was treated with azathioprine, corticosteroids, cyclophosphamide, plasma exchange, and cyclosporin A, but she remained erythroblastopenic and transfusion dependent for more than a year, at which time a promyelocytic transformation supervened. The authors propose that this sequence of events, hitherto unreported, is a manifestation of the multistep progression of CML.

Adult↗
PubMed1989

Primary wound closure in haemophiliacs undergoing dental extractions.

215 teeth were extracted in 62 haemophiliacs following a single infusion of factor VIII supplemented with antifibrinolytics. Tooth sockets were packed with Sorbacel gauze soaked with an antifibrinolytic. 1 group was sutured and the other left open. Primary closure of the extraction wound did not show direct effect on haemostasis. However, the size of the clot showed a statistically significant difference between the primary closure and open wound groups. The authors conclude that primary closure of the extraction wound protects the blood clot, makes the postoperative period more comfortable for patients and may subsequently decrease the risk of postoperative bleeding.

Administration, Topical↗