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Biomedical subjects

A M Tuncer

Publications and source records attributed to A M Tuncer.

At least 19 recordsLinked to original sources

Evaluation of coagulation in pediatric bone marrow transplantation patients.

A hypercoagulable state is frequently described in adult patients undergoing bone marrow transplantation (BMT). In this study, the coagulation profile of 29 children was prospectively investigated in the pre- and post-transplant period. A significant rise in the activated partial thromboplastin time (aPTT) values was detected on days 7 and 14 after transplantation. Moreover, an increase in the d-dimer level was also notable, regardless of the clinical condition of the patients. The other coagulation parameters investigated (i.e. protein S, protein C, anti-thrombin III, factor VIII, von Willebrand factor, and prothrombin time) remained essentially unchanged. However, hyper-fibrinogenemia was observed in all patients with chronic myeloid leukemia (CML) (n=5) before and after transplantation. In summary, in the present study pediatric bone marrow transplantation patients did not show a hyper-coagulable state after marrow infusion. However, a significant rise in PTT and d-dimer values were noted.

Adolescent↗

Effects of G-CSF and high-dose methylprednisolone on peripheral stem cells, serum IL-3 levels and hematological parameters in acute lymphoblastic leukemia patients with neutropenia: a pilot study.

Several agents, used either alone or in combination, have been shown to boost absolute numbers of PMLs and CD34+ stem cells in PB. In this study, we compared the effects of three different treatments, G-CSF, HDMP, and G-CSF + HDMP, for neutropenic patients (absolute PML count < 0.5 x 10(9)/l) who were on maintenance therapy for ALL with a control group who received no treatment. Hematological parameters, PB-CD34+33- and -CD34+ HLA-DR- stem cell numbers, and serum IL-3 levels were measured prior to, and a week after, the first day of treatment. WBC and absolute PML counts were significantly increased compared to pretreatment values in all treatment groups. However, peripheral CD34+ 33- and CD34+ HLA-DR stem cell numbers and serum IL-3 levels were increased significantly only in the G-CSF group. There was also a significant increase in serun IL-3 levels in the G-CSF + HDMP group. This study suggests that G-CSF may induce an increase in peripheral stem cell numbers, and that it supports hemopoietic recovery by increasing IL-3 in patients with chemotherapy-induced neutropenia.

Adolescent↗

CD34/CD117 co-expression in childhood acute leukemia.

CD117 protein is expressed by the primitive CD34 positive haemopoietic stem cells and also demonstrated on the blasts of 30-100% of AML cases, but rarely on lymphoblasts. Therefore several investigators have used CD117 expression to exclude lymphoblastic origin of blasts. However, conflicting results exist in the literature. We investigated CD34 and CD117 status at initial presentation of 232 children with acute leukemia. CD34 was commonly expressed in all types of acute leukemias, whereas CD117 molecule seemed to be a more specific marker for leukemia of myeloid origin being demonstrated on > 5% of blasts in 60 out of 73 cases of AML patients, but rarely detected in ALL (9/140 patients). Moreover, co-expression of CD34/CD117 was extremely rare on lymphoblasts with only 3/140 ALL patients demonstrating > 5% co-expression of CD34 and CD117, and therefore we suggest that it should be used in the exclusion of ALL.

Adolescent↗

The importance of cell size and surface marker analysis in childhood acute myeloblastic leukemia.

In order to evaluate the prognostic significance of cell size and surface marker expression, we evaluated 33 children with newly diagnosed acute myeloblastic leukemia by flow cytometry. We determined: the percentage of small, middle and large cells; large to small cell ratios (LS); large plus middle to small cell ratios (LMS); the percentage of surface markers expressed by each group of cell; the ratios of surface marker percentages expressed by the large blasts to that expressed by small blasts (LS for surface markers); and large plus middle blasts to that by small blasts (LMS for surface markers). For 'early prognosis', patients who could and could not achieve remission (n = 23 and 10) and for late prognosis, the patients who deceased or relapsed within the first 12 months of the treatment (n = 24) and who survived for more than 12 months (n = 9) were compared, in two classifications. CD3 percentages of the small cells of alive patients were significantly higher than that of dead or relapsed patients. LMS for CD3 and CD20 and LS for CD20 were higher in dead relapsed patients than that of alive patients. The total percentage of CD14 was significantly higher in dead relapsed patients than it was in the alive patients and CD3 was significantly higher in the group of patients who achieved remission than that of the patients who could not achieve remission. It was striking that, expression of CD3, CD7, CD22, CD33, CD14, CD15, CD34 increased or decreased as to cell size, whatever the prognosis. CD10, CD20 and CD13 were expressed on the large cells of the patients who could not achieve remission or died relapsed. We showed that, the blast cell size, individually does not have any prognostic significance in childhood AML and the prognostic significance of surface markers not only depends on their presence or absence but also on their relative configuration of expression by the blasts with different size.

Adolescent↗

Transferrin receptor on peripheral blood lymphocytes in iron deficiency anaemia.

The effect of iron deficiency anaemia (IDA) on CD71 expression by peripheral blood lymphocytes was studied in 43 children with iron deficiency anaemia. 18 healthy age-matched children were selected as the control group. 11 children with beta-thalassaemia trait were also studied. Lymphocytes bearing CD71 were enumerated by flow cytometric analysis of peripheral blood. At diagnosis, CD71+ peripheral lymphocytes (mean+/-SE) was 5.90+/-0-76% in patients with IDA and 12.60+/-0.98% in healthy controls (P=0.000). In beta-thalassaemia trait patients the peripheral blood CD71+ lymphocytes were 7.80+/-1.20%. In IDA patients there was a statistically significant correlation between the levels of CD71+ peripheral lymphocytes and haemoglobin value (P = 0.000). In 19 patients studied at days 0 and 30 of oral iron therapy, the number of peripheral blood CD71+ lymphocytes was shown to be increased from 5.90+/-0.76% to 12.11+/-1.21%. In severe IDA presence of a limited number of CD71+ peripheral blood lymphocytes indicated that severe IDA should be borne in mind when considering conditions responsible for the suppression of lymphocyte proliferation.

Adolescent↗

Multimedia and children in Turkey.

Multimedia will be regarded as essential tools for children to create their new world. The effects of television on young children's life have been well studied. Television differs, however, from other media, including the movies, in its pervasive impact on children. Children spend more time watching television than any other activity except sleeping. Overall 31% of children spent at least 4 hours a day watching television during weekday and 71.7% during weekend in Turkey. Television's influence on children is a function of the length of time they spend watching and the cumulative effect of what they see. Television may be a cause as well as a solution for many serious childhood problems. Excessive viewing of television has also been linked to aggressive behavior, violence, childhood obesity. On the other hand, television may act as a socializing agent and as a learning tool if the recommendations of American Academy of Pediatrics is learned by pediatricians, parents and broadcasters. The use of home personal computers in urban residence increased from 3.2% in 1993 to 6.5% by January 1998 in Turkey. Around 20% of computer households reported owing a modem. Internet has been using only for 5 years in Turkey. Nearly 40% of computer households also used CD-ROM equipment. The percentage of schools that have a computer laboratory is only 2.64%. On the other hand, multimedia allows students to move away from a uniform education for everyone to assert individual identity, liberalize education and management. It seems likely that, within the next few years, most of the countries with substantial internet infrastructure will use the internet as the major medium for disseminating information, including information on children. To prepare students for such a world demands that educational systems make the best possible use of all knowledge and technologies currently available.

Child↗

A comparison of the effect of high-dose methylprednisolone with conventional-dose prednisolone in acute lymphoblastic leukemia patients with randomization.

In this preliminary study the efficacy of high-dose methylprednisolone (HDMP) during remission-induction chemotherapy was evaluated on 166 children with acute lymphoblastic leukemia (ALL). The St. Jude Total Therapy Study XI protocol with minor modifications was used in this trial. Patients were randomized into two groups. Group A received conventional-dose (2 mg/kg/day orally) prednisolone, and group B received high-dose methylprednisolone (HDMP, Prednol-L, 900-600 mg/m2 orally) during remission-induction chemotherapy. Complete remission was achieved in 97% of the children. For the 80 patients who were followed up for 3 years, median follow-up was 44 (range 5-60) months and the 3-year event-free survival (EFS) rate was 68.5%) overall, 58.6% in group A and 78.4% in group B. The EFS among patients in group B was significantly higher than in group A (p=0.05). When we compared the 3-year EFS of groups A and B in the high-risk groups and high-risk subgroups with white blood cell (WBC) counts > or = 50 x 10(9)/l and age > or = 10 years, the survival rates were 45% versus 77.2%, 33% versus 78% and 45% versus 89%, respectively. During the follow-up of 162 patients, relapses were significantly higher in group A. Bone marrow relapses in 162 patients, and also in a subgroup of patients > or = 10 years of age were significantly higher in group A. These results suggest that HDMP during remission-induction chemotherapy improves long-term EFS, particularly for high-risk patients.

Adolescent↗

Dramatic resolution of pleural effusion in children with chronic myelomonocytic leukemia following short-course high-dose methylprednisolone.

High-dose methylprednisolone (HDMP) which can induce--differentiation and -apoptosis of myeloid leukemic cells has been shown to be very effective in the treatment of extramedullary infiltration (EMI) of children with acute myeloblastic leukemia (AML). In the present study 2 children with chronic myelomonocytic leukemia (CMML) who had pleural effusions were given a single daily dose of oral methylprednisolone (20 mg/kg or 30 mg/kg). In addition to dramatic improvement of respiratory symptoms, pleural effusions disappeared in four days in both patients possibly due to apoptotic cell death induced by HDMP treatment. Further studies are needed to determine whether high-dose corticosteroids are also effective on the resolution of pleural effusions associated with other malignant disease.

Adolescent↗

Effect of short-course high-dose methylprednisolone treatment on serum IL-2 levels in children with myelodysplastic syndromes: a pilot study.

Promising results in children with myelodysplastic syndromes (MDS) have been reported with high-dose methylprednisolone (HDMP) as a differentiation inducer, combined with cytotoxic chemotherapy. HDMP treatment has been shown to stimulate some cytokines in patients with acute leukemia. In the present study the effect of HDMP treatment on serum levels of interleukin 2 (IL-2) was evaluated in five children with MDS. Remarkable increases in serum IL-2 levels were observed 3 and 7 days after HDMP (30 mg/kg per day) treatment in three patients with chronic myelomonocytic leukemia (CMML). There was no correlation between the peripheral blood absolute lymphocyte counts and serum IL-2 levels. The results of this preliminary study indicate that the use of short-course HDMP treatment might be beneficial to increase the serum IL-2 level in patients with CMML.

Adolescent↗

Serum TNF-alpha, gamma-INF, G-CSF and GM-CSF levels in neutropenic children with acute leukemia treated with short-course, high-dose methylprednisolone.

High-dose methylprednisolone (HDMP, 20-30 mg/kg/day po) treatment has been shown to increase the number of bone marrow and peripheral blood CD34 positive progenitors and serum granulocyte-macrophage colony-stimulating factor (GM-CSF) levels in patients with ALL and AML. To investigate the effect of HDMP on some other hematopoietic regulatory cytokines, tumor necrosis factor-alpha (TNF-alpha), gamma-interferon (gamma-INF), granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6) were studied by microplate ELISA technique in 15 chemotherapy-induced neutropenic episodes of 14 children with acute leukemia (eight with ALL and six with AML) in whom HDMP was given alone (30 mg/kg/day po) for 4 days. The absolute neutrophil counts increased significantly in all neutropenic episodes on the fourth day of HDMP treatment. The TNF-alpha was 93.5 +/- 161 pg/ml in ALL and 78.3 +/- 61.4 pg/ml in AML before treatment and 76.1 +/- 160 pg/ml in ALL and 19.1 +/- 39.8 pg/ml in AML after treatment. The gamma-INF was 204.1 +/- 210.3 pg/ml in ALL and 130.8 +/- 138.3 pg/ml in AML before treatment and 28.6 +/- 50.5 pg/ml in ALL and 23.3 +/- 20.4 pg/ml in AML after treatment (P<0.05). Serum G-CSF and GM-CSF levels increased in all episodes (100%). The GM-CSF levels increased from 12.2 +/- 10.9 pg/ml to 36 +/- 24.7 pg/ml after treatment in ALL (P<0.05) and from 13.3 +/- 4 pg/ml to 45 +/- 48.1 pg/ml in AML (P<0.05). Serum G-CSF levels increased from 13.3 +/- 11.7 pg/ml to 83.3 +/- 86.8 pg/ml after treatment in ALL (P<0.05) and from 6.6 +/- 12.1 pg/ml to 28.3 +/- 11.3 pg/ml in AML (P<0.05). However, IL-6 levels were undetectable in all patients before and after therapy. These preliminary data suggest that short-course HDMP treatment could decrease serum TNF-alpha and gamma-INF and increase G-CSF and GM-CSF levels.

Adolescent↗

Morphologic evidence of apoptosis in childhood acute myeloblastic leukemia treated with high-dose methylprednisolone.

We have previously demonstrated that various subtypes of AML children respond to high-dose methylprednisolone (HDMP; 20-30 mg/kg/day) which could induce in vivo differentiation of myeloid leukemic cells to mature granulocytes. In this study we have evaluated whether apoptosis occurs in AML cells of patients treated by HDMP using morphological criteria. For light and electron microscopic examination bone marrow aspirates were obtained four days and two weeks after methylprednisolone (30 mg/kg/day) treatment from two children with newly diagnosed AML (AML-M3 and AML-M4). In both patients maturation of leukemic cells has previously been reported four days (in patient with AML-M3) and two weeks (in patient with AML-M4) after HDMP treatment. Electron microscopy revealed the characteristic ultrastructural changes of various stages of apoptosis four days after HDMP treatment in a case with AML-M3. Morphologic evidence of apoptosis induced by HDMP were also detected on Wright-stained and toluidine blue stained semithin sections of BM preparations in a patient with AML-M4 and AML-M3 respectively. These findings suggest that HDMP which could induce in vivo terminal differentiation in myeloid leukemic cells is also able to induce apoptosis in patients with AML. The possibility of HDMP-induced apoptosis should be evaluated in a larger series of patients with AML and other types of malignant tumors.

Apoptosis↗

The effect of short-course high-dose corticosteroid therapy on peripheral blood CD34+ progenitor cells in children with acute leukemia.

High-dose methylprednisolone (HDMP) treatment has been shown to induce the differentiation of myeloid leukemic cells to mature granulocytes in patients with acute promyelocytic leukemia and other subtypes of acute myeloblastic leukemia (AML). HDMP administration has also been shown to accelerate the recovery of leukocytes and increase bone marrow hematopoietic CD34+ progenitor cells in patients with acute lymphoblastic leukemia (ALL). In the present study, we evaluated the effect of short-course (4-day) HDMP treatment on peripheral blood (PB) CD34+ cells in patients with acute leukemia (AL). Fourteen children with AL who were receiving maintenance therapy were enrolled in this study. Methyl-prednisolone was given orally as a single daily dose of 30 mg/kg for only 4 days to nine children (three AML, six ALL) in whom chemotherapy-induced leukopenia (< 2 x 10(9)/L) was observed. Circulating CD34+ progenitor cells were determined by flow cytometry before (day 0) and 4 and 7 days after HDMP treatment. On days 4 and 7 after initiation of HDMP treatment, the number of PB CD34+ cells increased significantly (p < 0.05). Hematopoietic CD34+ progenitor cells were also determined in five patients with AL (two AML, three ALL) and chemotherapy-induced leukopenia who did not receive HDMP. The number of CD34+ cells was found to be significantly (p < 0.05) higher in the patients who received HDMP than in those who did not. Along with PB CD34+ progenitor cells, white blood cells (WBC), polymorphonuclear cells (PMN), and monocytes also increased significantly (p < 0.05) in patients treated with short-course HDMP. In conclusion, short-course HDMP treatment can be used to shorten the chemotherapy-induced leukopenic period in patients with AL, possibly by increasing the number of hematopoietic progenitor cells. Further studies are needed to evaluate the effect of this treatment on leukopenic patients with other malignancies.

Adolescent↗

High-dose methylprednisolone, low-dose cytosine arabinoside, and mitoxantrone in children with myelodysplastic syndromes.

High-dose methylprednisolone (HDMP) has been shown to induce differentiation of myeloid leukemic cells with a remarkable antileukemic effect in children with various subtypes of acute myeloblastic leukemia (AML), therefore we used HDMP in the treatment of four children with myelodysplastic syndrome (MDS). Two patients had refractory anemia with an excess of blasts in transformation (RAEB-t) with extramedullary infiltration (EMI), one had chronic myelomonocytic leukemia with pleural effusion, and one had RAEB. HDMP was administered orally at a single dose of 20-30 mg/kg/day combined with low-dose cytosine arabinoside (LD Ara-C) (10 mg/m2, 12-hourly s.c.) for 2 weeks. The treatment continued with mitoxantrone (10 mg/m2, i.v.) and Ara-C (5 mg/kg, i.v.) once a week for four doses followed by maintenance chemotherapy. All patients achieved hematologic remission 2-4 weeks after initiation of treatment. Extramedullary infiltration disappeared in all cases within 2 weeks to 3 months after initiation of therapy. With the exception of two patients who relapsed 6 and 24 months after remission, treatment could be stopped in others who remained in remission for 36 months without evidence of EMI; 6 months later one of them developed myelodysplastic relapse (RAEB). No side effects related to HDMP treatment were noted, but hyperleukocytosis developed in two patients who initially had high WBC counts. We suggest that the addition of HDMP with or without LD Ara-C to cytotoxic chemotherapy offers a promising alternative in cases not considered suitable for bone marrow transplantation.

Adolescent↗

The effect of high-dose methylprednisolone combined chemotherapy on CD34-positive cells in acute lymphoblastic leukemia.

The expression of CD34 antigen on the surface of bone marrow cells during remission induction was studied in 27 selected acute lymphoblastic leukemia (ALL) patients who were CD34 negative at presentation and were stratified to receive high-dose methylprednisolone (30 mg/kg/day po) or conventional-dose prednisolone (2 mg/kg/day po). Patients received either induction with L-Asparaginase, vincristine (VCR), and high-dose methylprednisolone [HDMP, 30 mg/kg/day po for 1 week, 20 mg/kg/day po for 1 week, and 20 mg/kg/day po every other day for 2 more weeks (20 patients)], or identical induction in which HDMP was replaced by prednisolone 2 mg/kg/day by mouth for 4 weeks (8 patients). Bone marrow cells from all patients were studied 1,2, and 4 weeks after initiation of treatment for expression of the CD34 antigen using a three-step indirect immunoperoxidase staining technique. In the 20 patients with ALL who received HDMP the percentage of normal bone marrow cells expressing CD34 was significantly higher (p < 0.05) than in the 8 patients who did not receive HDMP. The mean percentage of CD34-positive bone marrow cells during the fourth week was 17.2% in patients with ALL who received HDMP, whereas patients who received 2 mg/kg prednisolone per day had only 6.1% CD34 cells in the marrow. Absolute polymorphonuclear leukocyte (pmnl) count was also significantly higher in the patients who received HDMP in the second and third week of therapy [(absolute pmnl count was 2197.7/mm3 in the second week and 4091.8/mm3 in the fourth week in the patients who received HDMP compared to 974.4/mm3 and 1556.5/mm3 in the patients who did not receive HDMP) (p < 0.05)].(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Hyperglycemia, ketoacidosis and other complications of L-asparaginase in children with acute lymphoblastic leukemia.

We show Escherichia coli derived L-asparaginase complications observed in 14 of 136 acute lymphoblastic leukemia patients during remission induction therapy according to St. Jude Children's Hospital Total XI Protocol. We observed hyperglycemia in six patients; two of them had accompanying ketoacidosis. One of the cases with ketoacidosis had peritonitis and pancreatitis. Central nervous system symptoms such as convulsions and depression with personality changes (in one case) were observed in four of these six hyperglycemic patients. Intracranial bleeding and ischemic infarction were shown in cranial computed tomographies in two cases. Hypersensitivity reactions were observed in seven patients. Patients were randomly assigned into two groups and treated with conventional dose steroids or high dose methylprednisolone. Although the frequency of hypersensitivity reactions were lower in the high dose methylprednisolone group, one patient in this group had an anaphylactic reaction. These findings once again high-light L-asparaginase complications which are not dose dependent and can be life threatening.

Acidosis↗