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Biomedical subjects

U Ertem

Publications and source records attributed to U Ertem.

At least 19 recordsLinked to original sources

Serum levels and differential expression of CD44 in childhood leukemia and malignant lymphoma: correlation with prognostic criteria and survival.

BACKGROUND: The CD44, a cell surface proteoglycan, participates in a variety of function including tumor dissemination and metastasis. However, there are no available data on the prognostic significance of CD44 expression of tumor tissue correlated with serum sCD44 level in childhood leukemias and lymphomas. METHODS: Serum levels and leukemic cell tumor tissue expression of CD44 were detected in 54 children with acute leukemia and malignant lymphoma. Serum samples were obtained from all patients before treatment and during remission. Twelve age-matched healthy children were included as a control group. RESULTS: The serum CD44 levels were significantly higher in patients with Hodgkin's disease (HD), non-Hodgkin's lymphoma (NHL), Burkitt's lymphoma (BL) and acute lymphoblastic leukemia (ALL) than those in the control group. The median values were 1627.0, 1336.0, 1318.5, 1730.4, 902.7 ng/mL, respectively, and P<0.001, P<0.01, P<0.01, P<0.05 in comparisons, respectively. However, there was no significant difference between acute myeloid leukemia (AML) and the control group (median values: 900.3 and 902.7 ng/mL, respectively, P>0.05). Serum sCD44 levels significantly declined in HD, NHL and ALL patients who were in complete remission (median values: 684.0, 573.8 and 1101.1 ng/mL, respectively, P<0.05 in each comparison). Patients with HD had higher levels of serum sCD44 and correlated well with higher erythrocyte sedimentation rate (ESR), B-symptoms and advanced-stage disease (P<0.05, P<0.05 and P<0.01, respectively). Expression of CD44 was significantly high in patients with HD and NHL who were in advanced stages of disease. High serum CD44 level was also associated with high tumor tissue expression of CD44 in patients with HD and BL. In addition, patients with higher levels of serum sCD44, had a poorer outcome and survival than those with lower sCD44 levels in HD and NHL groups. CONCLUSIONS: A high serum sCD44 level and/or tumor tissue expression at diagnosis is associated with poor prognostic criteria and/or unfavorable outcome in childhood leukemias and lymphomas.

Adolescent↗

Natural killer cell numbers and cytotoxic activity in pediatric Hodgkin disease.

In this study peripheral blood natural killer (NK) cell activity was evaluated in 17 pediatric cases with Hodgkin disease (HD) (9 untreated, 8 in remission) and 20 age-matched healthy children. Peripheral blood CD16 and CD56 molecule expressions were also examined. No difference related to NK cell numbers and cytotoxic activity was detected at either stage of the disease. In cases in which long-term remission has been achieved (> or = 5 years) NK cell activity was slightly but not significantly increased in parallel with remission duration. Finally, no relation between NK cell activity and the etiology, prognosis, and severity of the disease has been established in children with HD.

Adolescent↗

High prevelance of chronic magnesium deficiency in T cell lymphoblastic leukemia and chronic zinc deficiency in children with acute lymphoblastic leukemia and malignant lymphoma.

Magnesium and zinc are the elements having essential roles in regulation of cell growth, division and differentiation. There have been some studies in the literature suggesting an association between the deficiency of these elements and the development of malignant disorders. In this study hair and serum zinc and magnesium levels were investigated in children with acute lymphoblastic leukemia (ALL) and malignant lymphoma (ML) at the time of initial diagnosis. Ten children with T-cell ALL, 10 children with B-precursor ALL, 5 children with Burkitt's Lymphoma (BL), 11 children with Hodgkin's lymphoma (HL), 10 children with non-Burkitt non-Hodgkin's lymphoma (NBNHL) and 12 age and sex matched healthy children as a control group were included in the study. Mean hair magnesium levels in all of the groups of the patients were lower than the levels in the control group but the difference was statistically significant only in the children with T cell ALL comparable to the controls (28.9+/-3.9 microg/g and 87.6+/-18.5 microg/g respectiveley, p<0,05). Mean serum magnesium levels in all the cohorts were not significantly different than those in controls (p>0.05 in each comparison). Mean hair zinc levels in the patients with T-cell, B-precursor ALL, BL, HL, NBNHL were 103.4+/-14.6 microg/g, 100.9+/-7.8 microg/g, 91.1+/-19 microg/g, 72.5+/-9.1 microg/g, 103.2+/-12.2 microg/g respectively. Each of these levels were significantly lower than the mean hair zinc levels of the control group (141.2+/-9.6 microg/g, p<0.05 in each comparison). Although mean serum zinc levels in all of the groups were also decreased, the differences were statistically significant only in the groups with B-precursor ALL, HL and NBNHL (75.9+/-5.29 microg/dl, 68.6+/-7.3 microg/dl, 85.7+/-5.5 microg/dl respectively) when compared with controls (105.1+/-9.9 microg/dl, p<0.05 in each comparison). Hair magnesium and zinc levels showed a positive correlation with each other in all the groups (r congruent with 0.5). No significant difference was found in the mean hair/serum magnesium and zinc levels between malnourished and nonmalnourished patients. In conclusion, regarding the results of our study and previous data in the literature chronic magnesium and zinc deficiency seems to be associated with the development of ALL and malignant lymphoma in a group of patients.

Child↗

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↗

Unusually high frequency of a 69-bp deletion within the carboxy terminus of the LMP-1 oncogene of Epstein-Barr virus detected in Burkitt's lymphoma of Turkish children.

Burkitt's lymphoma (BL) in Turkish children is commonly associated with Epstein-Barr virus (EBV) infection. The C-terminus of the latent membrane protein 1 (LMP-1) of EBV is essential for transformation and the 30-bp deletion detected in this region has been implicated to be associated with a more aggressive malignant phenotype. To understand the molecular mechanisms underlying EBV pathogenesis in BL of Turkish children, we analyzed 30-bp deletion and 33-bp variable repeat regions of the LMP-1 gene from paraffin-embedded tumor tissues of 30 BL patients (mean age 5.9 years). Primer pairs spanning the 30-bp deletion and 33-bp repeat regions were designed for amplification by polymerase chain reaction (PCR). The PCR-amplified products were analyzed by gel electrophoresis, Southern blot hybridization, and DNA sequencing. Twenty-eight (93%) of 30 BL biopsy samples were EBV positive as determined by PCR. Variable copy numbers (ranging from 4.5 to 7) of the 33-bp repeat of LMP-1 gene were detected in these EBV-containing tumor samples. To determine the frequency of the 30-bp deletion of the LMP-1 gene, we sequenced the amplimers encompassing this region. Analyses of DNA sequence of 28 Turkish BLs have disclosed four patterns: the first (32% (9/28)) is identical to B95-8 with no deletion, the second (11% (3/28)) is identical to Asian NPC CAO strain with 30-bp deletion, the third (46% (13/28)) is prevalent in Turkish BLs with a longer deletion (69 bp), and the fourth (11% (3/28)) consists of a mixture of 30-bp and 69-bp deletion. The occurrence of high frequency of the 69-bp deletion appears to have no correlation with the disease site. Mutations found in the CAO strain were also detected in the Turkish BL clustering at the amino acids 322, 334, 338 and 342; whereas mutations specific for Turkish BL were clustered at amino acids 326, 352 and 361. To assess the EBV genotype with the changes in C-terminus of LMP-1 gene, we performed genotyping by PCR to differentiate type A and B strain. All 28 patients were infected by type A EBV. Such a high frequency of the larger size (69 bp) deletion has never been reported. Ascertaining the role of this deletion in BL pathogenesis will require further study.

Amino Acid Sequence↗

Soluble L-selectin increases in the cerebrospinal fluid prior to meningeal involvement in children with acute lymphoblastic leukemia.

Soluble L-selectin was determined in the CSF samples of 20 children with CNS leukemia at the time they had blasts in CSF and/or clinical findings of CNS involvement; 17 CSF fluid samples were obtained from 17 of these 20 children, 29-91 days before the appearance of CSF cytological and/or clinical findings of CNS involvement; while 15 CSF samples were withdrawn from among the same group of children, after treatment of meningeal leukemia. In addition, CSF sL-selectin was also assayed in 17 children with ALL, who remained in complete remission at least for a year and, as controls, in 12 children without malignant or meningeal disorders. There was no significant difference in CSF sL-selectin levels between the children with ALL without evidence of meningeal involvement and the controls (1.34 +/- 0.21 ng/ml, 1.46 +/- 0.18 ng/ml respectively, p > 0.05). However, in children with CNS leukemia, not only at the time CNS involvement was diagnosed, but also 29-91 days before the diagnosis of CNS leukemia, the concentrations of the CSF sL-selectin (12.41 +/- 2.14 ng/ml, 7.70 +/- 1.60 ng/ml respectively) were significantly higher than those in controls (p < 0.001 and p < 0.01 respectively). After treatment and disappearance of the blasts in CSF, sL-selectin was found to be decreased and even normalized in the majority of children who had meningeal involvement (2.87 +/- 2.14 ng/ml). In 5 children, the CSF sL-selectin remained high, after the blasts in CSF had disappeared and CNS leukemia recurred within 3 months in 4 of these 5 children. In conclusion, assay of sL-selectin in CSF seems to be a good diagnostic tool in the detection of CNS involvement in children with ALL. This method may also be used as an indicator, in prediction of the CNS leukemia, which is going to develop.

Adolescent↗

Coexistence of life threatening chemotherapy related leukoencephalopathy, saggital sinus thrombosis and multiple organ failure in a child with acute lymphoblastic leukemia: an unusual case with clinical recovery.

A nine-year old girl with T cell acute lymphoblastic leukemia (ALL) had acute severe neurologic complications at the end of the remission-induction chemotherapy course. Thirty-six hours following triple intrathecal (IT) therapy and intravenous (IV) administration of L-asparaginase (L-asp), tetraplegia developed and she became unconscious. She had bouts of hypertension and persistent tachycardia unresponsive to digitalis therapy. Magnetic resonance imaging (MRI) showed multiple brain white matter hyperintensities and filling defects in the saggital sinus, suggesting thrombosis. Over the 40 days, in addition to her neurologic compromise she also had transient diabetes mellitus, severe hyperlipidemia, hypoproteinemia and edema, liver and heart failure and staphylococcus aureus sepsis with prolonged bone marrow depression. Despite, coexistence of all these chemotherapy related complications, her neurologic functions and multiple organ failure improved gradually. After a 70 days' period of interruption, chemotherapy was resumed and continued without any further complications. Although, the etiology of her extensive sensitivity to some drugs remains unclear, we believe that it is important to document these unusual events in this child.

Antineoplastic Combined Chemotherapy Protocols↗

Production of granulocyte colony stimulating factor, granulocyte macrophage colony stimulating factor, and tumor necrosis factor alpha during remission and infections in patients with acute leukemia.

We measured circulating serum levels of granulocyte colony stimulating factor (G-CSF), granulocyte macrophage colony stimulating comparable to the levels of these factors in 12 children with acute febrile infections without malignancy or hematological disorders and 15 age matched healthy controls. There were significantly elevated levels of G-CSF, GM-CSF and TNF alpha, in 12 children with infections without leukemia, as compared with controls. Also in 18 leukemic children with infections serum G-CSF and TNF alpha levels were significantly higher than those in the leukemic children without infection and healthy controls, whereas no significant difference was noted in the GM-CSF levels in these groups. Although elevation in TNF alpha levels in response to infections were similar in the children with and without leukemia, in the G-CSF levels lower elevation was noted in the leukemic children with infections as compared to the children with infections without leukemia. Despite leukopenia enhanced the production of G-CSF, even in leukopenic children with leukemia and infections, serum G-CSF levels were still lower than those for the children with infections without leukemia. We concluded that, the production of G-CSF and GM-CSF as a response to infection was deficient in the patients with acute leukemia in remission, probably due to the maintenance and reinforcement chemotherapy. Therefore, the use of recombinant G-CSF may be recommended in the infections of these patients.

Acute Disease↗

Burkitt's lymphoma in Turkish children: clinical, viral [EBV] and molecular studies.

Eighty-one Turkish children with Burkitt's lymphoma (BL) were observed during a period of 24 years (1968-1992). The diagnosis was established histologically according to WHO criteria. BL represented 48.5% of NHL in this series. The median age of patients was 5 years with a sex (M/F) ratio of 2.3/1. The most common primary site of tumor involvement at initial presentation was the abdomen (70.4%), which was followed by facial tumors, in particular the jaw and orbit (45.7%). The majority of the patients (84.0%) were in advanced stages (C and D) at initial diagnosis. Facial tumors observed in Turkish children with BL were more similar to African Burkitt's lymphoma than American or European cases. High titers of antibodies against VCA and EA of EBV were also observed in 32 recent cases of BL. Preliminary molecular and immunologic studies revealed EBV-DNA (type I) and T cell deficiency. The clinical presentation, median age, and association with EBV revealed that BL appears to be inbetween African and non-African types in Turkish children. This will be further elucidated in the future by direct examination of tumor cells for EBV and investigation of the molecular characteristics in these cases.

Adolescent↗

High risk subgroup of acute myelomonocytic leukemia (AMML) with orbito-ocular granulocytic sarcoma (OOGS) in Turkish children. Retrospective analysis of clinical, hematological, ultrastructural and therapeutical findings of thirty-three OOGS.

Thirty-three patients presenting with orbito-ocular granulocytic sarcoma (OOGS) and acute myelomonocytic leukemia (AMML) were diagnosed in Turkish children from 1963 to 1983. OOGS, characterized by exophthalmos, chemosis and orbital masses, was observed in 33 (27.2%) of 121 AML patients compared with 41 children of AMML without ophthalmic tumors during the same period. Eye tumor and bone marrow aspirates were also studied under light and electron microscopies. The comparison of the hematological parameters did not indicate any statistical difference between the groups. Despite similar chemotherapy regimens administered to all patients, the mean survival time was 8.7 months in the OOGS group, which is significantly shorter compared to those without OOGS (28.6 months) (p less than 0.01). These cases may be classified as a "high risk" subgroup of childhood AMML.

Adolescent↗

Once daily ceftriaxone for meningococcemia and meningococcal meningitis.

Twenty children with meningococcal disease (15 with meningococcal meningitis and 5 with meningococcemia without meningitis) were treated with ceftriaxone, 80 to 100 mg/kg/day for 4 days. An additional 22 patients with meningococcal disease (13 with meningitis, 9 with meningococcemia without meningitis) were treated with penicillin G. On the basis of the Damrosch-Stiehm scoring system, 19 patients were classified in the poor prognostic group and were treated with antishock therapy. Clinical recovery time and normalization of CSF were compared in two groups. When the complications were compared, necrotic skin lesions were more frequently seen in the penicillin G group than in those who received ceftriaxone. Ceftriaxone is an effective and safe drug and offers the advantage of once daily administration for treatment of meningococcal disease in pediatric patients.

Ceftriaxone↗

Zinc and anergy in pediatric Hodgkin's disease in Turkey.

Blood (serum, erythrocytes) and hair zinc levels were determined in 60 biopsy-proven pediatric Hodgkin's disease cases at diagnosis. Cellular immunity also was assessed through total lymphocyte counts, E-rosette formation, lymphoproliferative response (LP), and delayed cutaneous hypersensitivity tests to dinitrochlorobenzene, streptokinase-streptodornase, purified protein derivative and phytohemagglutinin (PHA) in some of these patients. Interestingly, anergic patients unresponsive to four antigens showed significantly more depressed serum zinc levels as well as decreased lymphoproliferative response to mitogen (PHA). A positive correlation could be shown between serum zinc level, cutaneous anergy and LP. A possible contributing role of zinc deficiency in defective cell mediated immunity in Hodgkin's disease was proposed, and administration of oral zinc, as a natural immunostimulant is considered in this lymphoma.

Adolescent↗

Zinc status and cellular immunity in pediatric Hodgkin's disease.

In the present study we investigated serum, plasma, RBC and hair zinc concentrations in pediatric Hodgkin's cases at initial presentation and in remission (measured by atomic absorption spectrophotometry). In addition, immune parameters such as total lymphocyte counts (TLC), E-rosette test (E-R), lymphocyte proliferative (LP) responses to PHA, and skin tests to four antigens were simultaneously investigated in some cases. Although all zinc levels were found to be significantly low before treatment, suggesting chronic zinc deficiency, serum and plasma zinc levels returned to normal during remission. A positive correlation could be detected only between serum zinc levels and lymphocyte blastogenic response to PHA. Hodgkin's patients with complete anergia also showed significantly lower serum zinc levels and LP responses to PHA than the patients without anergia.

Adolescent↗

Zinc levels of serum, plasma, erythrocytes and hair in Turkish women with anencephalic babies.

The present study revealed a significantly low zinc concentration, measured by atomic absorption spectrophotometry, in serum, plasma and erythrocytes of mothers with anencephalic babies as compared to two control groups of women. We feel that Turkey should be added to the list of geographic regions where zinc deficiency has been found together with a high rate of CNS malformations.

Anencephaly↗

Effect of nutrition on serum zinc concentration during pregnancy in Turkish women.

The serum zinc concentration in 101 pregnant women and 40 control subjects were determined by using atomic absorption spectrophotometer. The zinc levels were significantly low in 30 poorly nourished pregnant women compared to controls (P less than 0.01), whereas there was no statistical difference between the normal mean zinc values and that of well-nourished pregnant women (P greater than 0.05). This study revealed that nutrition is an important factor during pregnancy among Turkish women. In view of severe teratogenic effects of maternal zinc depletion in experimental animals as well as epidemiological evidence that maternal zinc deficiency could be a cause of severe congenital malformations of the central nervous system in humans, more extensive studies are definitely needed in Turkey.

Central Nervous System↗

Myocardial performance index combining systolic and diastolic myocardial performance in doxorubicin-treated patients and its correlation to conventional echo/Doppler indices.

This study was designed to evaluate the utility of myocardial performance index (MPI) in anthracycline cardiotoxicity. The MPI measures the ratio of total time spent in isovolumic activity (isovolumetric contraction time and isovolumetric relaxation time) to the ejection time, thus giving a global index combining systolic and diastolic myocardial performance. In this study, MPI was measured in 35 doxorubicin-treated children (aged 108.5+/-55.31 months, 23 males and 12 females) in sinus rhythm and 32 age-matched controls, and it was compared with conventional Doppler echocardiographic parameters. The isovolumetric contraction time was prolonged (38.37+/-24.43 vs 26.37+/-15.53, p <0.02) and ejection time was shortened (231.91 +/- 28.87 vs 256.21+/-19.55, p<0.001) in doxorubicin-treated patients compared to that in normal children. The isovolumetric relaxation time did not show significant difference between patients and control group (60.11+/-10.92 vs 61.06+/-12.12, p>0.05). MPI was significantly increased in doxorubicin-treated patients compared with that in control groups (0.42+/-0.07 vs 0.34+/-0.06, p<0.001), and significant correlation was observed between MPI and fractional shortening, ejection fraction, and left ventricular end diastolic and end systolic diameters (respectively, r = -0.508, p <0.002; r = -0.532, p<0.001; r = 0.467 p<0.005; r=0.606, p<0.001). Also, a weak correlation was found between MPI and duration of the disease and patient ages (r = 0.393, p < 0.02; r = 0.379; p < 0.02). However, there was no correlation between MPI and cumulative doxorubicin dose (r = 0.311, p > 0.05) and diastolic Doppler parameters in doxorubicin-treated patients. We think that MPI may be a useful parameter in monitoring left ventricular dysfunction in anthracyline-treated patients.

Antineoplastic Agents↗

Serum levels and differential expression of intercellular adhesion molecule-1 in childhood leukemia and malignant lymphoma: prognostic importance and relationship with survival.

Serum levels and leukemic cell-tumor tissue expression of intracellular adhesion molecule-1 (ICAM-1/CD 54) were detected in 54 children with acute leukemia and malignant lymphoma. Serum samples were obtained from all patients before treatment and after cessation of the therapy from malignant lymphoma cases and during remission from leukemic patients. Twelve age-matched healthy children were included as a control group. The serum ICAM-1 levels were significantly higher in patients with acute lymphoblastic leukemia (ALL) or Hodgkin's disease (HD) than those in the control group (median values: 350.9, 286.4, and 138.4 ng/mL, respectively; P < .01 in each comparison). However, there were no significant differences concerning serum ICAM-1 levels between the control group and each of the acute myeloid leukemia (AML), non-Hodgkin's lymphoma (NHL), and Burkitt's lymphoma (BL) case groups (median values: 235.7, 222.7, 195.9, and 138.4 ng/mL, respectively; P > .05 in each comparison). Moreover, serum soluble ICAM-1 levels significantly declined in ALL or HD patients who were in complete remission (median values: 185.0 and 145.4 ng/mL, respectively; P < .05 in each comparison). In HD patients high levels of serum ICAM-1 could be correlated with high ESR (P < .01), whereas no statistically significant difference could be found when serum ICAM-1 titers were compared with stages, B symptoms, and histological subgroups, probably because of the inadequate number of patients in each group. Expression of ICAM-1 was mainly attributed to lymphocytes, vessels, and weakly to Hodgkin's cells, and this was significantly high in patients who were in advanced stages of disease. High serum sICAM-1 level was also associated with poor outcome and survival. Determination of serum level and/or tumor tissue expression of ICAM-1 in HD and ALL might represent an additional, but probably not independent, disease-associated marker to be used in the evaluation and/or monitoring of treatment response in patients with HD and ALL.

Acute Disease↗