Biomedical subjects

Mualla Cetin

Publications and source records attributed to Mualla Cetin.

At least 19 recordsLinked to original sources

PubMed2006

Diamond-Blackfan anemia associated with beta-thalassemia trait.

A 14-month-old boy was referred to our hospital for evaluation of severe anemia. In the bone marrow aspiration smear, normal cellularity with severe erythroblastopenia (3%) was observed. The hemoglobin electrophoresis of the patient and his father were compatible with the beta-thalassemia trait. Because macrocytosis of Diamond-Blackfan anemia (DBA) is masked by microcytosis of beta-thalassemia trait, the diagnosis of DBA co-existing with beta-thalassemia trait might be challenging. We report herein a case of DBA co-existing with beta-thalassemia trait in a Turkish boy.

Adolescent↗

PubMed2006

Transfusion-transmitted virus prevalence in Turkish patients with thalassemia.

In hematology patients on chronic transfusion regimes, liver diseases are frequent, and mostly related to the agents transmitted by blood products and concominant iron deposition in liver. Besides hepatitis B (HBV) and C (HCV) viruses, new viral agents like hepatitis G virus (HGV) and TorqueTeno virus (TTV) are identified in these patients, although their association with any pathology or disease is not yet proved. In the present work, the authors studied the clinical importance of TTV in Turkish multitransfused patients with thalassemia. Forty-six healthy and 57 thalassemic patients were enrolled in the study. TTV was detected in serum samples by 3'-UTR nested PCR. Transaminase and ferritin levels, hepatitis B and C virus markers and number of transfusions were interpreted for possible association with TTV infection. As a result, TTV was detected in 63% of the thalassemia and 54% of the control patients. Prevalence of TTV infection, clinical features, laboratory data, and annual transfusion numbers of TTV-positive and -negative patients were not observed to be statistically significant. In conclusion, in Turkish patients with thalassemia, TTV infection cannot be considered as a risk factor for liver disease.

Adolescent↗

PubMed2006

Can renal leukemic infiltration cause hypertension in children?

Out of 334 children with acute lymphoblastic leukemia who were treated with St Jude Total XI and Total XIII chemotherapy protocols were investigated and 21 (6.3%) were hypertensive. The incidence of tumor lysis syndrome was higher in the hypertensive group than in the nonhypertensive group (28.6% vs. 11.5%) (P = 0.035). There were no differences between patients treated with high-dose methylprednisolone and prednisolone St Jude Total XI and Total XIII, St Jude Total XIII LR and St Jude Total XIII HR groups in respect of the above-mentioned parameters. Central nervous system involvement, skeletal system involvement, abdominal lymphadenopathy, elevated lactate dehydrogenase and leukocyte count, French-American-British types and immunophenotypes were not found to be statistically significant to the development of hypertension (P > 0.05). We found that renal leukemic infiltration is a risk factor in hypertension development (P = 0.04) and hypertension is a risk factor for renal parenchymal disorder in the follow-up period (P = 0.0001). Six patients presenting with hypertension in the first week of disease therapy were evaluated for renal parenchymal disorder and glomerular filtration rate abnormality in the follow-up period. Glomerular filtration rate abnormality was found in 1 and renal scintigraphic dimercaptosuccinic acid abnormalities (reduced uptake and dilated hypoactivity) were found in 4 patients. Hypertension was also found to be a risk factor for renal parenchymal disorder in the follow-up period.

Adolescent↗

PubMed2006

Hepatitis B immunoglobulin in combination with lamivudine for prevention of hepatitis B virus reactivation in children undergoing bone marrow transplantation.

There is little information in literature about the use of hepatitis B immunoglobulin (HBIg) in recipients of bone marrow transplantation (BMT). Here, we report two children who received IV HBIg (Hepatect-CP) and lamivudine treatment during BMT course for either patient or donor hepatitis B virus (HBV) viremia. A four-year-old girl underwent a fully human leukocyte antigen-matched allogeneic BMT for thalassemia major from her mother positive for hepatitis B surface antigen (HBsAg). A 12-yr-old boy with chronic myeloid leukemia, positive for HBsAg and HBV-DNA received a fully HLA-matched allogeneic BMT from his sister in the first chronic phase of the disease. HBIg was successfully used in both cases to prevent HBV reactivation of the recipients. The results of our observations are encouraging and we suggest that HBIg in combination with lamivudine may be used in such cases especially in post-transplant early period to prevent HBV reactivation.

Bone Marrow Transplantation↗

PubMed2005

The neurologic complications in pediatric acute lymphoblastic leukemia patients excluding leukemic infiltration.

This study presents retrospective analyses of 20 acute lymphoblastic leukemia (ALL) patients who developed neurologic complications (except leukemic infiltration). These subjects represent 9.9% of 203 ALL patients aged 16 years or younger followed in our hospital between March 1991 and January 2003. Fourteen male and six female patients, whose ages ranged between 6 and 168 months, developed 24 episodes of neurologic complications after the diagnosis of ALL. The most common complication was meningitis, which developed in six (25%) episodes, and two thirds of the patients who had meningitis were evaluated to be iatrogenic. Cerebral infarct and venous thrombosis were detected in five (21%) of the episodes. In two (8%) episodes progressive cerebral dysfunction developed after radiotherapy. The remaining 11 (45%) episodes are due to varying types of complications. Interestingly, one patient had abundant histiocytes exhibiting hemophagocytosis in the cerebrospinal fluid (CSF) examination and this patient was subsequently diagnosed with fungal meningoencephalitis, by further investigation. Six (30%) patients died; epilepsia developed in five (25%) patients in the follow-up period and the remaining nine (45%) are healthy. By close follow-up and effective treatment of thrombosis and, especially, of infections including iatrogenic meningitis in developing countries, the morbidities and mortalities of these complications can be decreased.

Adolescent↗

PubMed2005

Nonradioactive vitamin B12 absorption test evaluated in controls and in patients with inherited malabsorption of vitamin B12.

BACKGROUND: Current tests for evaluation of vitamin B(12) absorption are problematic because they involve the use of radioactively labeled vitamin B(12). We describe a vitamin B(12) absorption test that circumvents this problem. METHODS: We measured cobalamin or transcobalamin saturated with cobalamin (holo-TC) 24 h after three 9-microg doses of vitamin B(12) given orally at 6-h intervals. We studied 17 patients with inherited malabsorption of vitamin B(12) attributable to Imerslund-Grasbeck syndrome (n = 13) or intrinsic factor deficiency (n = 4), their obligate heterozygous biological parents (n = 19), and healthy controls (n = 44). RESULTS: In the patients, the median (range) change of holo-TC after the B(12) load was not significant [1 (-42 to 5) pmol/L], nor was the change of cobalamin [-3 (-32 to 22) pmol/L], consistent with a lack of measurable active or passive absorption. In controls, however, the median (range) increases of holo-TC and cobalamin were 26 (-6 to 63) pmol/L and 41 (-37 to 109) pmol/L, respectively. Similarly, the parents showed increases of 23 (-2 to 47) pmol/L and 27 (-15 to 94) pmol/L. The mean areas under the ROC curves (95% confidence intervals) were 0.97 (0.93-1.0) for holo-TC and 0.87 (0.79-0.94) for cobalamin, distinguishing patients from controls. At a cutoff of 6 pmol/L for holo-TC, the diagnostic sensitivity (95% confidence interval) was 100 (81-100)%, and the diagnostic specificity was 92 (82-97)%. CONCLUSION: Measurement of holo-TC after administration of vitamin B(12) is a promising approach for evaluating vitamin B(12) absorption.

Absorption↗

PubMed2005

CD34/CD117 positivity in assessment of prognosis in children with myelodysplastic syndrome.

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal stem cell disorders that are characterized by morphology identifying dysplastic changes in one or more cell lineages, peripheral blood cytopenias and a propensity to evolve into secondary acute myeloid leukemia (AML). CD34 is commonly expressed in all types of childhood leukemias, whereas CD117 is a reliable and specific marker to detect leukemia cells committed to myeloid lineage. Co-expression of CD34/CD117 may strongly suggest the diagnosis of AML (Rytting ME. Pediatric myelodysplastic syndromes. Curr hematol Rep 2004;3(3):173-7. May; Uçkan D, Hiçsönmez G, Yetgin S, Gürgey A, Cetin M, Karaağaoğlu E, et al. CD34/CD117 co-expression in childhood acute leukemia. Leukemia Res 2000;24:201-6.). We describe the case of a 22 month-old-girl with MDS and Down syndrome who was presented with severe anemia and thrombocytosis at diagnosis, transformed into AML-M7. In our patient, CD34 and CD117 markers were positive on the blast cells of the BM 6 months before the chemotherapy decision. As the disease progressed, CD34/117 co-existence was increased and MDS transformed into AML. As a result, an increase in CD34 and CD117 positivity of the BM blast cells may be associated with a higher risk of leukemic transformation.

Antigens, CD34↗

PubMed2005

The mutational spectrum of PTPN11 in juvenile myelomonocytic leukemia and Noonan syndrome/myeloproliferative disease.

Germ line PTPN11 mutations cause 50% of cases of Noonan syndrome (NS). Somatic mutations in PTPN11 occur in 35% of patients with de novo, nonsyndromic juvenile myelomonocytic leukemia (JMML). Myeloproliferative disorders (MPDs), either transient or more fulminant forms, can also occur in infants with NS (NS/MPD). We identified PTPN11 mutations in blood or bone marrow specimens from 77 newly reported patients with JMML (n = 69) or NS/MPD (n = 8). Together with previous reports, we compared the spectrum of PTPN11 mutations in 3 groups: (1) patients with JMML (n = 107); (2) patients with NS/MPD (n = 19); and (3) patients with NS (n = 243). Glu76 was the most commonly affected residue in JMML (n = 45), with the Glu76Lys alteration (n = 29) being most frequent. Eight of 19 patients with NS/MPD carried the Thr73Ile substitution. These data suggest that there is a genotype/phenotype correlation in the spectrum of PTPN11 mutations found in patients with JMML, NS/MPD, and NS. This supports the need to characterize the spectrum of hematologic abnormalities in individuals with NS and to better define the impact of the PTPN11 lesion on the disease course in patients with NS/MPD and JMML.

Child↗

PubMed2005

Hereditary juvenile cobalamin deficiency caused by mutations in the intrinsic factor gene.

Hereditary juvenile megaloblastic anemia due to vitamin B12 (cobalamin) deficiency is caused by intestinal malabsorption of cobalamin. In Imerslund-Grasbeck syndrome (IGS), cobalamin absorption is completely abolished and not corrected by the administration of intrinsic factor (IF); if untreated, the disease is fatal. Biallelic mutations either in the cubilin (CUBN) or amnionless (AMN) gene cause IGS. In a series of families clinically diagnosed with likely IGS, at least six displayed no evidence of mutations in CUBN or AMN. A genome-wide search for linkage followed by mutational analysis of candidate genes was performed in five of these families. A region in chromosome 11 showed evidence of linkage in four families. The gastric IF (GIF) gene located in this region harbored homozygous nonsense and missense mutations in these four families and in three additional families. The disease in these cases therefore should be classified as hereditary IF deficiency. Clinically, these patients resembled those with typical IGS; radiocobalamin absorption tests had been inconclusive regarding the nature of the defect. In the diagnosis of juvenile cobalamin deficiency, mutational analysis of the CUBN, AMN, and GIF genes provides a molecular characterization of the underlying defect and may be the diagnostic method of choice.

Chromosome Mapping↗

PubMed2005

Myeloprotective effect of short-course high-dose methylprednisolone treatment before consolidation therapy in children with acute myeloblastic leukemia.

In our previous studies, short-course high-dose methylprednisolone (HDMP) has been shown to shorten the chemotherapy-induced neutropenic period by stimulating the CD34(+) hematopoietic progenitor cells in children with acute leukemia. In this study, we investigate the role of short-course HDMP on induction of a myeloprotective effect when administered before consolidation therapy consisting of high-dose cytosine arabinoside and daunorubicin. Thirty-four consecutive newly diagnosed children with acute myeloblastic leukemia (AML) who received 64 courses of consolidation regimen were entered into the study. The patients received HDMP (group A) at a daily dose of 30 mg/kg methylprednisolone starting 4 days before the initiation of consolidation therapy. The control group did not receive HDMP (group B). There were no differences in the white blood cell (WBC) and absolute neutrophil counts (ANC) between group A (at day -4) and group B (at day 0) at the beginning of the study (medians: 3 x 10(9)/L vs. 3.2 x 10(9)/L and 1.5 x 10(9)/L vs. 1.7 x 10(9)/L, respectively). The WBC count increased significantly from 3 x 10(9)/L to 6.4 x 10(9)/L, and ANC increased from 1.5 x 10(9)/L to 3.9 x 10(9)/L after 4 days of HDMP treatment in group A (P < 0.01). Following high-dose chemotherapy, the median values of WBC and ANC also remained higher than the control values during the 16 days of the follow-up period. The neutropenic period was significantly shorter in the HDMP group than in the control group (9 +/- 5.2 days vs. 22 +/- 4.7 days) (P < 0.05). The duration of hospitalization and the interval between two chemotherapy cycles were significantly decreased in group A when compared group B (9 +/- 2.7 vs. 14 +/- 2.7 days; 22 +/- 4.7 vs. 26 +/- 4.2 days, respectively) (P < 0.05). Moreover, following consolidation therapy, the number of patients with ANC values below 0.5 x 10(9)/L was lower in group A when compared the group B. In conclusion, the administration of short-course (4 days) HDMP before high-dose chemotherapy has been found to be beneficial for reducing the duration and severity of neutropenia. Further studies with short-course HDMP are required to evaluate its myeloprotective effects in patients with other malignancies.

Adolescent↗

PubMed2005

Bone mineral density and serum bone turnover markers in survivors of childhood acute lymphoblastic leukemia: comparison of megadose methylprednisolone and conventional-dose prednisolone treatments.

During recent decades, the survival rate after childhood acute lymphoblastic leukemia (ALL) has improved substantially; consequently, the long-term side effects of ALL and its treatment have gained attention, of which osteoporosis is one of the most important. The purpose of the present study was to compare the influence of different treatment protocols that include high-dose methylprednisolone (HDMP) versus conventional-dose prednisolone (CDP) for remission-induction therapy on bone mineral density (BMD) and serum bone turnover markers in survivors of childhood ALL after cessation of chemotherapy. Thirty-six boy and 23 girl survivors, treated for ALL, were cross-sectionally studied, at a mean age of 11.7 years (range 6-19). Group 1 (n = 30) received CDP therapy (prednisolone, 2 mg/kg/day, orally) and group 2 (n = 29) received HDMP therapy (prednol-L, 900-600 mg/m2, orally). All other therapies were similar in both groups. Cranial irradiation was added for high-risk patients as soon as possible after consolidation therapy. We found that mean lumbar spine BMD z score value was -1.75 (0.83) SDS in group 1 and -1.66 (1.21) SDS in group 2. There is no difference between both groups (P = 0.736). The mean BMD z scores of prepubertal and pubertal patients were not significantly different in both groups. Comparison of serum bone turnover parameters of the patients revealed no difference between the two groups. Stepwise regression analysis revealed that lumbar spine BMD z scores was predicted by height SDS and the time past since cessation of therapy, but not age at diagnosis, BMI SDS, cranial radiotherapy, and puberty. Our study results showed that HDMP treatment did not deteriorate the bone mass any more than CDP treatment. These results proved that high-dose steroid therapy over a short period of time in remission-induction treatment would not affect the bone mass any more adversely than would conventional doses approximately 3 years after cessation of chemotherapy.

Adolescent↗

PubMed2005

Secondary hemophagocytic lymphohistiocytosis in Turkish children.

Between January 1998 and January 2005, a total of 18 children 2 weeks-72 months of age were diagnosed as having secondary hemophagocytic lymphohistiocytosis. The frequency of secondary hemophagocytic lymphohistiocytosis among total hospitalized patients during this period was 0.05% (18 of 34,250). Of the 18 patients, 8 (44.5%) had bacterial infections; cytomegalovirus and Epstein-Barr virus infections were present in 5 (28%) and 1 (5.5%), patient, respectively. Leishmaniasis was diagnosed in 2 patients (11%), and herpes simplex virus was diagnosed in 2 patients (11%). Six patients died during treatment, and 1 patient was lost to follow-up. The survival rate was 61%.

Animals↗

PubMed2005

Electrolyte abnormalities at diagnosis of acute lymphocytic leukemia may be a clue for renal damage in long-term period.

The objective of this study was to determine the frequency of electrolyte perturbations and their relationship with leukemic status before and after chemotherapy in patients with acute lymphocytic leukemia. Blood biochemistry, liver and renal function tests, and renal sonograms were examined at diagnosis and during induction therapy in 334 patients. Renal and electrolyte disturbances were then studied in 116 patients between 3 and 110 months after cessation of the St. Jude chemotherapy treatment protocol. Glomerular filtration rate, electrolyte, protein, and beta-2-microglobulin levels were determined in fresh urine samples, and serum electrolyte levels were examined in blood samples. Renal sonographic examinations and scintigraphic examinations were performed with DMSA and MAG-3. Renal leukemic involvement was detected by sonographic examination in 32 patients who had also presented with hyperphosphatemia or hyperuricemia. Patients with electrolyte disorders at diagnosis were less likely to have tumor lysis syndrome during induction chemotherapy. This may be explained by correction of their electrolyte disorders at the time of diagnosis, which may protect them from tumor lysis syndrome. Hypocalcemia and hyponatremia at the time of diagnosis were found to be significant initial risk factors for renal scan abnormalities and microproteinuria, respectively, during the late therapy period (P < 0.05). Electrolyte abnormalities and renal changes were commonly observed before and after therapy for leukemia. Patients presenting with hypocalcemia and hyponatremia should be examined for microproteinuria and should undergo renal scanning during the late therapy period.

Adolescent↗

PubMed2005

Answer to hypotonia: a simple hemogram.

A 1-year-old boy with weight loss, decreased activity, and psychomotor regression is presented. He was subjected to an extremely detailed evaluation, including electroencephalography (EEG) and magnetic resonance imaging (MRI), until a simple hemogram in our center revealed that he had macrocytic anemia with megaloblastic changes in the bone marrow. His history revealed that he had been exclusively breast-fed by his vegetarian mother. Further investigations showed low serum vitamin B12 concentration, methylmalonic aciduria, and homocysteinemia, indicating that the macrocytic anemia was due to vitamin B12 deficiency. This boy represents a case of macrocytic anemia and hypotonia owing to vitamin B12 deficiency that developed because of exclusive breast-feeding by a vegetarian mother.

Anemia, Macrocytic↗

PubMed2004

Evaluation of kidney damage in patients with acute lymphoblastic leukemia in long-term follow-up: value of renal scan.

In order to evaluate potential long-term kidney damage of childhood leukemia and risk factors affecting renal damage, we studied 116 children treated for acute lymphoblastic leukemia (ALL) using the St. Jude Total XI and XIII protocols in 1991-1998. The median follow-up period after the completion of treatment was 35 months. The following parameters were examined: urinalysis, urinary creatinine (Cr), calcium (Ca), phosphorus, beta2-microglobulin, glomerular filtration rate (GFR), tubular phosphorus reabsorption (TPR), and renal function tests. Radiological evaluation included renal ultrasonography (US), and renal scans with DMSA or MAG-3 were performed. Blood chemistry and renal US patients were normal in all patients except two. GFR, TPR, urinary Ca/Cr, beta2-microglobulin, and renal scan were abnormal in 19.0%, 16.4%, 13.8%, 6.0%, and 40.5% of patients, respectively. The abnormality rate in GFR was significantly higher in patients <2 years of age. TPR abnormality was found to be significantly higher in patients who did not have G-CSF. An abnormal renal scan was associated with Hb < 10 g/dL, kidney infiltration, or hypertension at presentation and also occurred patients who underwent methotrexate treatment with frequent intervals during the follow-up period. Patients should be followed-up after cessation of therapy with the conventional tests mentioned above. In case of any abnormality, further detailed tests should be performed; renal scan seems to be more predictive for renal damage.

Adolescent↗

PubMed2004

Genetically heterogeneous selective intestinal malabsorption of vitamin B12: founder effects, consanguinity, and high clinical awareness explain aggregations in Scandinavia and the Middle East.

Selective intestinal malabsorption of vitamin B(12) causing juvenile megaloblastic anemia (MGA; MIM# 261100) is a recessively inherited disorder that is believed to be rare except for notable clusters of cases in Finland, Norway, and the Eastern Mediterranean region. The disease can be caused by mutations in either the cubilin (CUBN; MGA1; MIM# 602997) or the amnionless (AMN; MIM# 605799) gene. To explain the peculiar geographical distribution, we hypothesized that mutations in one of the genes would mainly be responsible for the disease in Scandinavia, and mutations in the other gene in the Mediterranean region. We studied 42 sibships and found all cases in Finland to be due to CUBN (three different mutations) and all cases in Norway to be due to AMN (two different mutations), while in Turkey, Israel, and Saudi Arabia, there were two different AMN mutations and three different CUBN mutations. Haplotype evidence excluded both CUBN and AMN conclusively in five families and tentatively in three families, suggesting the presence of at least one more gene locus that can cause MGA. We conclude that the Scandinavian cases are typical examples of enrichment by founder effects, while in the Mediterranean region high degrees of consanguinity expose rare mutations in both genes. We suggest that in both regions, physician awareness of this disease causes it to be more readily diagnosed than elsewhere; thus, it may well be more common worldwide than previously thought.

Anemia, Megaloblastic↗

PubMed2004

Children with acute myeloblastic leukemia presenting with extramedullary infiltration: the effects of high-dose steroid treatment.

To evaluate whether children with acute myeloblastic leukemia (AML) presenting with extramedullary infiltration (EMI) have different clinical, morphologic features and prognosis from children without EMI, a 127 consecutive previously untreated children with AML were entered in this study. Fifty-one children (40%) had EMI at diagnosis and 27% of these showed multiple site involvement. Twenty-seven of 127 children (21%) presented myeloid tumors. No age related differences in the incidence of EMI was noted. However, analysis of clinical and biological features at diagnosis showed that WBC count > or =50 x 10(9) l(-1), hepatosplenomegaly >5 cm, FAB AML-M4 and AML-M5 subtypes and CD13, CD14 expression of bone marrow (BM) leukemic cells (>20%) were more frequent in children with EMI. Two consecutive treatment protocols were used. In both protocols remission was achieved with combined high-dose methylprednisolone (HDMP) as a differentiating and apoptosis inducing agent with mild cytotoxic chemotherapy (low-dose cytosine arabinoside (LD Ara-C), weekly mitoxantrone and Ara-C or 6-thioguanine). Administration of short-course (4-7 days) HDMP (20-30 mg/kg per day) alone resulted in a remarkable decrease in peripheral blood, BM blasts and in the size of EMI in responding patients. In both protocols, remission rate in patients with EMI was 71 and 80%, which was lower than that of the patients without EMI (87 and 89%). This may be attributed to the higher frequency of unfavorable features in children with EMI. However, in patients who presented with myeloblastoma and treated with a more intensive post-remission therapy (AML-94), the 4-year disease-free survival (DFS) and event-free survival (EFS) rates were not found to be significantly different from children who had no EMI (P>0.05). Whereas, the outcome of children who presented with gingival infiltration did not improve. In further studies, the prognostic significance of different localisation of EMI and the effect of addition of HDMP to cytotoxic chemotherapy should be explored in larger series.

Acute Disease↗

PubMed2004

Metamizole sodium-induced severe aplastic anemia and its recovery with a short-course steroid therapy.

The authors treated a girl with severe aplastic anemia that developed following urinary tract infection. She was referred to our hospital for bone marrow transplantation. The detailed medical history of the patient revealed iatrogenic metamizole sodium overdose that was given during her infection. She responded to a 3-day, high-dose methylprednisolone therapy and consequent conventional dose steroid. The authors observed at first partial and subsequently complete remission of all the hematologic parameters of the patient within 30 days and 4 months, respectively. This case suggests that the history of drug use should be questioned carefully in the patients with aplastic features. Steroid treatment may be an appropriate alternative therapy for aplastic anemia if associated drug use is detected in the medical history.

Adolescent↗