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.

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.

An intensive approach to the treatment of disseminated BCG infection in a SCID patient.

There is an appreciable mortality associated with BMT in patients with SCID and advanced BCG infection. We present a girl with T-B+ SCID complicated by spina ventosa and disseminated BCG osteitis after receiving a fully matched sibling marrow transplant. Considerable progression characterised by two clinical activations and multiple pleural and perivertebral abscess formations occurred with conventional anti-mycobacterial chemotherapy. She finally recovered with full immune reconstitution after BMT and intensive treatment comprising five conventional and alternative agents that she received for 36 months. No side-effects and/or complications have been seen other than hearing loss.

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.

The effect of continuous subcutaneous insulin infusion on insulin binding to erythrocytes in diabetes mellitus.

The effect of continuous subcutaneous insulin infusion (CSII) on glycaemic control and insulin binding to erythrocytes was studied in six diabetic patients. A marked improvement in blood glucose control during CSII was observed in these patients previously on conventional therapy. Specific 125I-insulin binding to erythrocytes of the diabetics before the institution of CSII was significantly lower than that of age-, weight- and sex-matched nondiabetic subjects, 6.5 +/- 0.1% vs. 9.8 +/- 0.3% (P less than 0.05). After 4-6 months of CSII, insulin binding was restored to normal levels. This normalization in insulin binding to erythrocytes of patients on CSII was due to a 35% increase in active binding sites, together with a small change in binding affinity.

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.

Decreased iron and zinc absorption in Turkish children with iron deficiency and geophagia.

Oral iron and zinc tolerance tests were performed in 12 patients between 8 and 21 years of age, with iron deficiency anemia and geophagia. Decreased iron and zinc absorption were detected respectively in patients against the elevated absorption curves in control subjects. Iron and zinc malabsorption may be an additional feature of the syndrome characterized by geophagia, iron deficiency anemia, hepatosplenomegaly, hypogonadism and dwarfism observed in Turkey and Iran.

Serum zinc levels, lymphocyte counts and functions in pediatric Hodgkin's disease.

Serum zinc levels, total lymphocyte counts, cutaneous reactivity to three intradermal antigens and the in vitro lymphoblastic transformation response to PHA were evaluated in 24 children with Hodgkin's disease and 20 control cases. Serum zinc level was measured by atomic absorption spectrophotometer (Perkin Elmer M 103) in Hodgkin's cases and found to be significantly decreased in the whole group of patients and reached the lowest level in LD type and the IVth stage of disease. The overall response to PHA was reduced in Hodgkin's cases. It was significantly low in the group of LD subtype. Delayed cutaneous hypersensitivity reactions were also markedly decreased in the IV stage and MC, LP subtypes of Hodgkin's patients. Our preliminary results disclosed a relationship between serum zinc level and the lymphocyte abnormalities in Hodgkin's disease.

Determination of the mean cell age of erythrocytes from diabetic subjects with pyruvate kinase.

The pyruvate kinase activity of erythrocytes from normal and diabetic subjects was examined in order to establish this enzyme as a valid indicator of mean cell age in the studies of age-dependent erythrocyte functions. This study reveals that the enzyme activity in the erythrocytes was not affected by the condition of diabetes and suggests that it may provide a simple means for the determination of cell age in erythrocyte insulin binding studies. Present data further indicate that the mean cell age of the erythrocytes from diabetic patients was not significantly different from normal although insulin binding to erythrocytes was markedly reduced when compared with that in the normal subjects.

Zinc levels in maternal and cord blood serum during normal deliveries.

Concentration of zinc was determined by atomic absorption spectrophotometry in 90 maternal and paired cord blood sera. Forty non-pregnant age-matched women served as controls. The mean value of zinc in maternal sera was 73.4 +/- 1.5 micrograms/dl whereas the mean zinc level in cord blood of normal neonates was 114 +/- 2.4 micrograms/dl. Significantly low levels of zinc were found in pregnant women as compared to their non-pregnant counterparts, who had a mean zinc level of 113.8 +/- 3.3 micrograms/dl. The study indicates that zinc values in cord blood were significantly higher than those of the mothers, and no correlation existed between the values of zinc in maternal and cord blood sera.

Effects of zinc supplementation on linear growth in beta-thalassemia (a new approach).

Linear growth was evaluated in 32 patients with beta-thalassemia major. At the beginning of the study of 40.6% of the patients were below the 10th percentile with biochemical evidence of zinc deficiency. Effects of zinc supplementation on growth velocity (height) were assessed in a controlled manner. Twenty-one children received oral zinc sulphate for a period of 1 to 7 years (15 early- and 6 late-supplemented cases), while the remaining 11 thalassemics were maintained only on conventional transfusion therapy. The mean height velocity of early-zinc supplemented children was significantly greater than that of normal children (P less than 0.01). An increase in height was also observed in the patients who received delayed zinc retardation. The present study demonstrated that zinc deficiency is one of the factors responsible for retarded linear growth in beta-thalassemia major. Only the patients who received zinc supplementation showed an acceleration of growth in height. Administration of zinc could, therefore, be considered as an effective adjuvant therapy in homozygous beta-thalassemia.

T-lymphocyte sub-populations in orbito-ocular granulocytic sarcoma (OOGS) and acute myelocytic leukemia (AML): a preliminary study.

The aetiology of GS remains obscure and a little is known about the immune competence of these patients. Interestingly, all children with OOGS were from low 'socio-economic status' and showed diminished delayed hypersensitivity reactions and reduced T cell counts (E-R) in our previous observation. We present herewith a preliminary data on evaluation of T cell sub-populations determined by monoclonal antibodies (CD3, CD4, CD8 and CD16 cells) in 10 patients with OOGS and AML prior to treatment. Quantitative immunoglobulin determinations of IgA, IgM, IgG were also made. The percentage of Pan T (CD3), CD4, CD8 cells were significantly lower than those in the controls (p < 0.01). The immunoglobulin levels were slightly elevated suggesting normal B cell functions. In conclusion, these preliminary findings suggest that cellular immune deficiency may be an underlying cause.

Ocular granulocytic sarcoma (chloroma) with acute myelomonocytic leukemia in Turkish children.

In a series of 166 leukemic children from Turkey, 56 had acute myelomonocytic leukemia (AMML). Seventeen boys and 3 girls presented with chloroma-like deposits (granulocytic or myeloid sarcomas) in the eye and orbit, all showing AMML on initial study of blood and marrow. The ocular lesions responded rapidly to antileukemic therapy. Laboratory studies of AMML cases revealed no cytogenetic or immune defects, and Epstein-Barr virus titers were normal. A group-specific (GS-3) antigen (type-C virus?) was identified in one patient by radioimmunoassay of orbital tumor extracts. It is not clear what factors contribute toward the myelomoncytic differentiation of leukemia and its localization in the eye and orbit, but opportunities for further study are enhanced by reports of a predisposition to ocular chloroma among leukemic children in Africa, Egypt, and Japan.

Ultrastructural studies on AMML and ocular granulocytic sarcoma.

The ultrastructural analysis of the leukemic cells in twelve cases with AMML was considered a valuable tool in the diagnosis of this type of leukemia. Furthermore intracytoplasmic structure resembling virus like particles were observed in three bone marrow and one eye sample of the patients studied. The role of C-type RNA viruses in the etiology of leukemia was discussed.

Fanconi's aplastic anemia, analysis of 18 cases.

A total of 18 patients within the age range of 5-13 years, 12 male and 6 female, are diagnosed as having Fanconi's aplastic anemia on the basis of congenital abnormalities, pancytopenia, bone marrow hypoplasia, and chromosomal and hematologic analysis. The hereditary and familial basis of Fanconi's aplastic anemia was apparent in this series. Common abnormalities were growth retardation, café au lait spots, hyperpigmentations, microcephaly, phalange deformities, mental retardation, and hypogenitalism; chromosome abnormalities were detected in the majority of our cases. Mast cells were observed in the bone marrow in most of the patients. 1 case developed acute myelomonocytic leukemia.

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.

Geophagia in Turkey: iron and zinc deficiency, iron and zinc absorption studies and response to treatment with zinc in geophagia cases.

A brief summary of the research carried out on the problem of geophagia is reported in this paper. Geophagia was a common finding among Turkish children and women in villages, associated with severe iron deficiency anemia in addition to zinc depletion. The syndrome characterized by geophagia, iron deficiency anemia, growth retardation, hypogonadism and zinc deficiency has been observed in both sexes in Turkey for several decades. Zinc deficiency has been also shown by our group in this syndrome. The decreased concentrations of zinc in serum, plasma, RBC, hair and urine were measured by atomic absorption spectrophotometer. Oral iron (both inorganic and radioactive iron) and zinc absorption tests were carried out with and without clay and revealed decreased iron and zinc absorption in some cases with prolonged geophagia. Therefore, malabsorption of iron and zinc was considered to be an additional and/or a new finding in the syndrome. Furthermore, Turkish clay most probably inhibits zinc absorption in a way similar to its inhibition of iron absorption. It was worthy of observation that some Turkish patients with this syndrome had a thalassemia-like appearance with similar skull-bone changes. Finally, growth retardation and delayed puberty were shown to be corrected by oral zinc treatment for 6-month terms. Linear growth and sexual maturation were found to be greater in the zinc-treated group than in the controls.