Hodgkin's disease in Turkish children: a clinical and histopathologic analysis.

Fifty-one cases of Hodgkin's disease in Turkish children under 15 years of age were clinically analyzed, and 40 cases were evaluated histopathologically according to the Rye Conference classification. Complete clinical, laboratory, and radiologic findings for each patient were examined. Most patients were of low socioeconomic class, and nearly all were Caucasian. The most common presenting clinical sign was cervical lymph node enlargement; hepatosplenomegaly was noted in 18 patients. Nearly three times as many males as females were found among the patients whose diseases were histologically analyzed, and most of the children with Hodgkin's disease were in the first decade of life. Classification of the cases revealed a predominance (67.5%) of the mixed cellularity (MC) type. Of 40 patients analyzed, 34 had disease in clinical stage IV, mostly of the MC type. The data indicated a correlation of the high incidence of the MC type of Hodgkin's disease with the socioeconomic and environmental conditions in Turkey.

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.

Hair zinc levels in healthy and malnourished children.

In this study the hair zinc levels of 115 healthy subjects, 50 girls and 65 boys, between the age groups 0 to 15 years were determined by using atomic absorption spectrophotometry. The hair zinc levels obtained generally agree with those reported in the literature. The hair zinc levels of the subjects were studied as a function of age, sex and color of hair. It was found that the levels of hair zinc increased as a function of age, whereas no statistically significant differences with respect to sex and color of hair were observed. In a protein-calorie malnourished group of 11 girls and six boys between the ages 0 to 3 years, it was found that the hair zinc levels were significantly higher than a group of healthy subjects of the same age range. In a protein-calorie malnourished group of seven subjects no correlation was found between hair zinc and serum levels.

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.

Orbito-ocular granulocytic sarcoma (OOGS) and acute myeloblastic leukemia (AML) with duplication of Philadelphia chromosome.

A 6-year-old Turkish boy with bilateral orbito-ocular granulocytic sarcoma and AML is described. Cytogenetic studies on peripheral blood disclosed an abnormal hyperdiploid population with a double Ph chromosome. Despite intensive chemotherapy, he achieved only partial remission. Repeated cytogenetic studies on bone marrow during relapse revealed the persistence of double Ph chromosome. The aggressive course and the short survival time of this patient, despite adequate chemo-radiotherapy, may be explained by the presence of the double Ph chromosome.

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.

Levels of zinc in plasma, erythrocytes, and hair, and levels of serum copper in patients with retinitis pigmentosa in Turkey.

This study was made on 100 patients with retinitis pigmentosa and 23 of their relatives. Their plasma, erythrocyte, and hair Zn and serum Cu levels were compared with those of a control group of 14 healthy persons. No statistically significant difference in these levels was found between the patients with retinitis pigmentosa and the relatives or controls.

Late effects of chemoradiotherapy in pediatric Hodgkin's disease.

We treated 137 Turkish children with biopsy-proven Hodgkin's disease, followed up between the years 1964 and 1989. Most patients were treated and were in advanced stage with histological subtype of mixed cellularity (67.5%). Radiotherapy (Mantle form) and/or MOPP, ABVD and OPPA combination chemotherapy regimens were used in 75.84% of patients. The follow-up period in these patients ranged from 5 to 24 years. The late effects in 28 patients who were evaluated for the late sequelae of chemoradiotherapy are presented. Seven out of 28 patients showed retarded sexual maturation. Testicular and ovarian functions were assessed in 11 patients, all of whom showed elevated serum FSH levels and 2 azoospermia. Analysis of thyroid functions was carried out in patients receiving radiotherapy to the neck. The thyroid gland was palpable in 6 patients. Further analysis showed diffuse hyperplasia in 5 and nodular in 1 patient. The nodule was excised and reported as "nodular colloidal goiter". Two patients had elevated TSH levels. "Swan-like neck" was observed in 3 patients who had received 40 to 42 Gy radiotherapy to the neck. Cirrhosis due to chronic hepatitis B infection was diagnosed in 2 patients as an unusual late complication. The secondary malignancy occurred in only 1 case in the form of "fibrosarcoma". The second neoplasm was probably radiation-induced as it occurred in the field of prior radiotherapy.

Granulocyte-macrophage colony stimulating factor (rh-GM-CSF) in the treatment of chemotherapy-induced neutropenia.

Neutropenic pediatric patients with solid tumors and malignant lymphomas were treated with recombinant granulocyte-macrophage colony stimulating factor (rh-GM-CSF). Eleven patients, including seven lympho-reticular malignancies, two Ewing's sarcoma and one patient in each group with the diagnosis of nasopharyngeal rhabdomyosarcoma, malignant mesenchymal tumor, entered the study. Six were females and five were males, the mean age was 10.4 yr, the range was 4 to 21 years. rh-GM-CSF was given at the dose of 5 micrograms/kg s.c. daily, starting either on the day following the last day of cytotoxic chemotherapy or when ANC < 1000/ml was determined. All patients received rh-GM-CSF for a total of seven days. Hematopoietic recovery occurred in all children except one. The response to rh-GM-CSF was achieved in a mean time of 7.4 days. Tolerance to rh-GM-CSF treatment was good. Adverse events were documented as fever, nausea, vomiting, fatigue, chills and itching. Sagittal sinus thrombosis developed in one patient 5 days following the completion of chemotherapy and rh-GM-CSF cycle. In conclusion, rh-GM-CSF can be applied during the intensive chemotherapy schedules of pediatric cancer patients.

Maternal hair zinc concentration in neural tube defects in Turkey.

Hair zinc concentration was measured in samples taken from 57 mothers who delivered infants with neural tube defects (NTD) (mainly anencephaly). Control groups consisted of 30 healthy mothers with normal offspring and 37 nonpregnant women from middle-income backgrounds. Zinc concentration was also measured in the hair of eight infants with NTD (four being anencephalic). The mean maternal hair zinc concentration in the NTD group (128.2 +/- 38.9 micrograms/g) was lower than that of the control women (p less than 0.001), whereas the mean hair zinc level of malformed babies (250.4 +/- 85.2 micrograms/g) was significantly higher than that of normal infants (193.4 +/- 39.2 micrograms/g) (p less than 0.05). Maternal nutritional zinc deficiency was thought to be one of the factors responsible for NTD in Turkey.

Selenium status of healthy Turkish children.

Selenium concentrations, in blood plasma, red blood cells, hair of 61 healthy children, ages 0-14 yr, were determined using hydride generation atomic absorption spectrometry. Starting from late lactation period, selenium concentrations in all these matrices were found to be increasing with age. A good correlation was found between erythrocyte and plasma, hair and plasma, and hair and erythrocyte selenium concentrations. Although plasma, erythrocyte, and hair selenium concentrations of girls seemed to be higher than that of boys (only in erythrocytes), selenium concentrations of girls were found to be significantly (p < 0.002) higher than that of boys, 71 +/- 9 ng/mL, vs 65 +/- 10 ng/mL, respectively. Selenium status of Turkish children is found to be lower than that found in the literature; marginal selenium deficiency could be important in the development of some selenium deficiency related diseases. There is a need for extension of this study to healthy children from different regions in Turkey and to different disease states.

[Use of thymus hormone in the demonstration of acute T-null cell lymphocytic leukemia]. / L'impiego dell'ormone timico nel riconoscimento della leucemia linfocitica acuta (LLA) a cellule T0.

The Authors studied the effect of the human serum thymic factor on the peripheral-blood leukocytes from ALL patients, by testing the frequency of the E+cells by means of the e rosette assay before and after cell incubation with the above mentioned factor. In 3 out of 24 patients tested, the thymic factor incubation of peripheral-blood mononuclears increased the number of E+cells. The shift from R to E+cells caused by the human serum thymic factor occurred among null cells (E-, SM-Ig-). The possible value of the test in investigating whether a T0 leukemia might really exists is pointed out, as well as its prospective importance in monitoring the variations of the immature T cell counts in relationship to the patient's treatment and his disease course.

Changes of trace minerals (serum iron, zinc, copper and magnesium) in thalassemia.

We have determined serum Zn, Fe, Cu and Mg in 42 patients aging from 3 months to 22 years with homozygous beta-thalassemia and thalassemia intermedia and in 36 control subjects of the same ages. Serum zinc was significantly decreased. Serum copper and iron were increased, but magnesium was found to be at normal levels.