Platelet factor 3 in normal subjects and patients with renal failure.

Two tests were used to differentiate abnormalities in release of platelet factor 3 (PF3) from quantitative deficiencies of this factor in normal subjects and in patients with renal failure. The first test was an assay which determined availability of PF3 (PF3-A time) and involved the use of a mixture of patient's platelet-rich plasma (PRP) and normal platelet-poor plasma (PPP) in a fixed ratio (1:8). The second test was similar but used "frozen and thawed" platelets to obtain a quantitative estimate of PF3 (PF3-F time). An abnormal PF3-A time was found in approximately three-quarters of 55 patients with renal insufficiency; 43 of these had chronic and 12 had acute renal failure. This abnormality was present both in patients with and without hemorrhagic manifestations, although it was slightly more common in bleeders. The PF3-F test was abnormal in approximately one-third of the bleeding patients and one-quarter of the non-bleeders. The PF3-A time returned to normal or was significantly shortened 24-48 hr after peritoneal or hemodialysis. Studies on patients who were not dialyzed showed no statistically significant correlations between the PF3-A time and either the serum urea nitrogen, creatinine, calcium, or phosphorus. Furthermore, the PF3-A time was not affected by guanidinosuccinic or guanidinoacetic acids. We therefore conclude that the demonstrable platelet abnormality in patients with uremia is produced by an unknown dialyzable material. The mean plasma clot retraction of uremic patients was also significantly different from the mean plasma clot retraction or normal controls. However, unlike the PF3-A time, the abnormality of plasma clot retraction was not immediately affected by dialysis. Correction of plasma clot retraction did occur after repeated dialyses.

The importance of blast cell DNA content for prognosis of childhood acute lymphoblastic leukemia.

The prognostic value of cellular DNA content measured by static cytophotometry was evaluated in 69 children with acute lymphoblastic leukemia (ALL) using the pretreatment distribution of the DNA content in blast cells of bone marrow and peripheral blood. The median follow-up of the whole group of patients was 45 months. Aneuploidy was detected in 71% of children, most of them showing a hyperdiploid content (DNA index greater than 1.05). The duration of complete remission was significantly longer in patients with distinct hyperdiploid DNA content (DNA index greater than 1.16) than in those with less hyperdiploid and diploid DNA content (DNA index less than 1.16). The results achieved by static cytophotometry were compared with flow cytometry analysis and with cytogenetic investigations of chromosomal abnormalities in leukemic cells. Higher correlation was found between flow cytometry and cytogenetics. Flow cytometry proved to be a more convenient method for detection of the DNA content in leukemic cells than static cytophotometry.

[Use of flow cytometry in the diagnosis of acute leukemias in childhood]. / Vyuzití prutokové cytometrie v diagnostice akutních leukémií detského veku.

The authors examined, using the method of flow cytometry, 56 children with acute lymphoblastic leukaemia. Leukaemic cells of the bone marrow aspirate and peripheral blood were examined on a FACS 440 apparatus for establishment of the diagnosis before treatment was initiated. Individual immunological subtypes were differentiated by means of a panel of monoclonal antibodies. 80.5% of acute lymphoblastic leukaemias originated from different developmental stages of B cells, 12.5% were formed by leukaemias from T cells and 7% were non-differentiated leukaemias. The mean follow-up period in the group was 33 months. According to the therapeutic results children with leukaemia ensuing from precursors of B cells had a more favourable prognosis than children with T leukaemia and children with non-differentiated leukaemia. Quantitative examination of nuclear DNA of leukaemic cells revealed in 55% of the patients of the group aneuploidy with clear predominance of hyperdiploidy, 45% of the patients suffered from diploidy. The least number of relapses was recorded in the investigation period in children with hyperploid acute lymphoblastic leukaemia. The proliferating activity of leukaemic blasts was expressed by the number of cells in the S + G2M stage of the cellular cycle and was higher in the bone marrow than in peripheral blood but did not differ in individual immunological subtypes or in diploid leukaemias. The authors were not able to prove its prognostic importance. Flow cytometry is a rapid and sensitive diagnostic method which makes it possible to characterize more satisfactorily the heterogeneous group of acute lymphoblastic leukaemias.

[Familial hemophagocytic lymphohistiocytosis]. / Familiární hemofagocytující lymfohistiocytosa.

This rare fatal disease of infants and early childhood occurred in seven children from four families. Six children died during 2-4 weeks from the beginning of disease, the last one has survived two years with cytostatic treatment. The disease was characterized by intermittent fever, hepatosplenomegaly and progressive pancytopenia as well as hyperbilirubinemia, hyperlipemia and hypofibrinogenemia. In addition to substantial enlargement of the liver and spleen prevailing autoptic findings were infectious complications due to severe immune defect or signs of hemorrhagic diathesis. Lymphocytes and histiocytes phagocytizing blood cells were increased in bone marrow, liver, spleen, often brain and further organs. Problems of differential diagnosis and pathogenesis were discussed.

[Familial cerebral degeneration with myocardial involvement and dyserythropoiesis]. / Familiární cerebrální degenerace s postizením myokardu a dyserytropoesou.

A combination of dyserythropoietic anaemia, encephalopathy and cardiomyopathy was found in two siblings of different sex. They shared the same clinical history and pathomorphology what made authors suppose that it was a new not yet described syndrome with presumed autosomal recessive heredity.

[Histiocytic syndromes in childhood]. / Histiocytární syndromy v detském veku.

The authors submit an account of the new classification of histiocytic diseases in childhood, they mention contemporary views on their aetiology, pathogenesis, advances in diagnosis and therapy. The paper is supplemented by case-histories from the authors' own practice.

[Factors affecting the prognosis of acute lymphoblastic leukemia in childhood]. / Faktory ovlivnující prognózu akutní lymfoblastické leukémie v detském veku.

The authors tried to test the value of some clinical and laboratory characteristics for the prognosis of acute lymphoblastic leukaemia (ALL) in a group of 69 children treated according to three different protocols. The results were evaluated by methods of one-dimensional and multidimensional analysis. The absolute number of blasts in the peripheral blood stream and initial leucocytosis during establishment of the diagnosis proved to be the most important risk factors influencing the prognosis of the patients. Other adverse signs for the prognosis of ALL in the group were a mediastinal tumour, L2 type of leukaemic blasts according to the morphological FAB classification and age above 10 years when the diagnosis was established. The patient's sex, immunophenotype of the leukaemic blasts, chromosomal abnormality of the karyotype in the leukaemic cells, marked hepatosplenomegaly, thrombocytopenia, haemoglobin values and PAS reaction in the blasts, did not affect the therapeutic results in the author's group of patients.

[Advances in the treatment of acute lymphoblastic leukemia in childhood: experience with intensive protocol treatments]. / Pokrok v lécbe detské akutní lymfoblastické leukémie: zkusenosti s lécbou pomocí intenzívních protokolu.

The authors analyzed a group of 64 children with acute lymphoblastic leukaemia (ALL) treated according to three protocols of different intensity. The best therapeutic results were obtained in children treated according to the most intensive protocol of the West German Multicentre Investigation BFM 83 which is graded as to its intensity with regard to the degree of risk of an adverse course. Successful remission in the entire group of patients was 93%, one third of the children developed during the investigation period a relapse of the basic disease. 12% of the children died during remission from complications of treatment. The surprising agreement of therapeutic results of different protocols after three years' complete remission is apparent from the fact that early relapses during the first two years of treatment, implying resistance to administered therapy, are at present the greatest problem of effective treatment which is not resolved even by the ever increasing intensity of treatment. In the conclusion the authors define the group of patients with a high risk of early relapse for whom new therapeutic procedures must be sought.