Giammarco Surico

Angiogenesis extent and expression of matrix metalloproteinase-2 and -9 correlate with progression in human neuroblastoma

In human tumors changes in angiogenesis and expression of extracellular matrix-degrading enzymes occur simultaneously during invasion and metastasis. Tissues from 20 biopsies of human neuroblastoma (NB) were investigated immunohistochemically by using an antibody against factor VIII to determine their microvessel number, and by in situ hybridisation to determine the expression of mRNA of the matrix metalloproteinase-2 (MMP-2) and MMP-9. The extent of angiogenesis and the expression of the MMP-2 and MMP-9 mRNA were upregulated in advancing stages. These in situ data suggest that angiogenesis and degradation of extracellular matrix occur simultaneously with NB tumor progression.

Parenteral iron supplementation for the treatment of iron deficiency anemia in children

Abstract. Iron-deficiency anemia impairs growth and intellectual development in children, which can be reversed only by early diagnosis and iron supplementation. Oral supplementation can efficiently replace stores, but in many cases parenteral iron is needed. Unfortunately some adverse reactions have limited its use in children. We compared the efficacy and safety of intramuscular and intravenous administration in 33 evaluable children with severe iron deficiency and/or iron-deficiency anemia who failed to respond to oral iron supplementation. Nineteen children received intravenous infusion and 14 intramuscular injections. All children showed recovery from iron-deficiency anemia, with statistically similar improvement in hemoglobin levels. The duration of treatment was longer in those receiving intramuscular injection. Parenteral iron therapy for the treatment of iron-deficiency anemia is a rapid, easy, and definitive solution to a long-troubling situation. We suggest the use of parenteral iron, in particular intravenous iron, in children who do not recover from severe iron-deficiency anemia after oral therapy. We should consider the physical and neuropsychological sequelae of long-lasting iron deficiency in children and the fact that oral supplementation is less likely to replace iron stores.

Age-related changes in the proliferative kinetics of phytohemagglutinin-stimulated lymphocytes. Analysis by uptake of tritiated precursors of DNA, RNA and proteins, and by flow cytometry

We have examined the age-related changes in the kinetics of lymphocyte proliferative responses to phytohemagglutinin by flow cytometry and by the uptake of tritiated thymidine, uridine and leucine. The lymphocyte suspensions used in these experiments were obtained by umbilical cord blood samples of full-term normal newborns and from the peripheral blood of young (under 30-year-old) or aged (more than 70-year-old) healthy donors. The results indicate that the cord blood lymphocytes were activated by phytohemagglutinin to incorporate tritiated precursors of proteins, RNA and DNA at a more rapid rate than the lymphocytes from young or old donors in the first 3 days of in vitro culture. Flow cytometry confirmed higher percentages of activated cycling cells in umbilical cord blood after 24 h of culture. The lymphocytes from old donors incorporated significantly lower amounts of tritiated precursors of DNA and RNA than lymphocytes from young donors at the third day of culture. The uptake of tritiated leucine by lymphocytes from old donors was significantly reduced up to the sixth day of culture. On the contrary, at the eight day of culture, lymphocytes from old donors incorporated significantly higher amounts of labeled DNA, RNA and protein precursors. In agreement with these findings, flow cytometry demonstrated a trend towards higher percentages of cycling cells in the lymphocyte cultures from old donors after 6 and 8 days. These results indicate an age-related decline in the rate of lymphocyte blastogenesis after in vitro PHA stimulation and suggest that after a delayed PHA-induced activation, the lymphocytes from aged donors have a near-normal ability to proliferate.

Polyclonal hypergammaglobulinemia at the onset of acute myeloid leukemia in children.

Abstract Polyclonal hypergammaglobulinemia (PHG) associated with hematological malignancies is a rare occurrence. We reviewed our series of 47 children with AML in order to define the prevalence of PHG and its prognostic value in achieving complete remission (CR) after induction treatment. Patients were stratified by immunoglobulin levels into two groups: with PHG and without PHG. CR reached after induction chemotherapy was considered a positive response. Conditional exact tests were used for the statistical analysis; conditional maximum likelihood estimates of the odds ratio (OR) were obtained. Significance levels (p) were determined from two-tailed tests. Twenty-two of 38 (57.9%) evaluable children showed PHG. Children with PHG and AML were more likely to be in CR after first induction treatment (OR=6.25, p=0.021), independent of sex, age at diagnosis, white blood cell count, percentage of blasts in the bone marrow, FAB phenotype, and treatment protocol. Infections seemed to positively influence early treatment response (p=0.038). PHG and infections were not statistically associated (p=0.16). PHG may result from the uncontrolled stimulation of B lymphocytes by cytokines. Infections or transfusions may act as triggers for the immune system, leading to the antileukemic effect seen in patients with AML and PHG going into spontaneous remission. It could be that this activation caused the larger number of CRs observed in our series. Clarification of why PHG exerts a positive influence on children with AML could help us to understand the ways by which the organism is able to control a malignant disease.