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Biomedical subjects

M Kalmanti

Publications and source records attributed to M Kalmanti.

67 records · Page 4Linked to original sources

Ondansetron and tropisetron in the control of nausea and vomiting in children receiving combined cancer chemotherapy.

Ondansetron (Zofron, Glaxo) and tropisetron (Navoban, Sandoz) are selective serotonin (5HT3) antagonists that have proven very effective in the prevention of vomiting and nausea in adults and children receiving cancer chemotherapy. This study compared the efficacy of the two agents in the prevention of vomiting and nausea in children receiving chemotherapy for solid tumors and blood malignancies. A total of 23 children were studied in 205 chemotherapeutic cycles (116 one-day regimens and 89 multiple-day regimens). In 102 chemotherapeutic cycles the children received ondansetron as an antiemetic agent in a dose of 5 mg/m2 30 min before chemotherapy was given and then 4 mg/m2 every 8 h i.v. (group A) and in 103 cycles they received tropisetron in one dose of 0.2 mg/kg 24 h-1 i.v. (max dose 5 mg) 30 min before cytotoxic drugs administration every day they received chemotherapy (group B). The response was defined as complete in the absence of nausea and vomiting per 24 h of chemotherapy, as partial given the presence of 1-4 events of vomiting and/or nausea less than 5 h per 24 h, and as failure if there were more than 4 events of vomiting and/or nausea for more than 5 h per 24 h of chemotherapy. The response of the two groups was studied independently and depending on the degree of emetogenicity of the chemotherapeutic agents, which were divided into mildly, moderately, and highly emetogenic. The comparison of the two groups not taking into consideration the emetogenicity of the chemotherapeutic agents showed that ondansetron was more effective in 1-day regimens (P = .023), whereas the two agents were equally effective in multiple-day regimens (P = .2). The statistical analysis depending on the emetogenicity of the chemotherapeutic agents showed increased efficacy of ondansetron in mild (P = .017) and moderately emetogenic chemotherapeutic agents, whereas there was no difference in the highly emetogenic drug group. Ondansetron is found to be more effective than tropisetron in controlling acute nausea and vomiting in children receiving mild and moderately emetogenic chemotherapeutic drugs, although there is no difference in the efficacy of both antiemetic agents when highly emetogenic drugs are administered.

Adolescent↗

Primary benign erythrocytosis with high erythropoietin levels and an early erythropoietin-sensitive population in the peripheral blood.

Primary erythrocytosis diagnosed in a 10-month-old female and followed for 12 years is described. The erythrocytosis was associated with an abnormally elevated set point of erythropoietin production in which the sensitivity fluctuated independently, but corresponded to the alterations in the oxygen-carrying capacity of the blood, when the hematocrit was lowered by phlebotomies. Extensive work for secondary erythrocytoses failed to demonstrate a recognizable cause for this abnormal erythropoietin production. Erythroid cell cultures from peripheral blood mononuclear cells showed the existence of at least two populations: one consistent with dramatic expansion of the erythron in keeping with enhanced sensitivity to endogenous erythropoietin, and the other consistent with the features of typical colonies derived from burst-forming units-erythroid (BFU-Es), seen in normal peripheral blood on days 12 to 14 of culture. The expanded population was characterized by the appearance of single colonies on days 4 to 6 and enormous response to the increasing amounts of erythropoietin, which enhanced their number, size, and maturation. The combination of clinical and in vitro data as well as the absence of any abnormality in the erythropoiesis of the parents and sibling suggest that the erythrocytosis in this child represents a new form with a benign course.

Cells, Cultured↗

Effect of granulocyte colony-stimulating factor on chemotherapy-induced neutropenia in children with cancer.

We investigated the effects of recombinant granulocyte colony-stimulating factor (G-CSF) administration on duration of neutropenia, antibiotic therapy, and hospitalization days in 25 children with malignancies (Group A: 12 leukemia and lymphoma; Group B: 13 tumors) who were undergoing chemotherapy. We compared the effect of G-CSF with a control group of 21 children with equivalent diseases and chemotherapy that did not receive G-CSF treatment. All 25 children received 5 micrograms/kg/day of G-CSF at the end of chemotherapy courses when absolute neutrophil counts were < or = 1000/mm3. The effect of G-CSF on median neutrophil profiles, antibiotic therapy, and hospitalization days was studied for both groups at the 1st and 4th cycle of chemotherapy. During both cycles, children who received G-CSF showed a faster rise of absolute neutrophil count (P < 0.001) and fewer hospitalization days (P < 0.05), and not as many received systemic antibiotic therapy (P < 0.0001). We conclude that G-CSF accelerates neutrophil recovery in chemotherapy-induced neutropenia in childhood malignancies.

Adolescent↗

Efficacy of recombinant human granulocyte colony-stimulating factor and recombinant human granulocyte-macrophage colony-stimulating factor in neutropenic children with malignancies.

The difference between the effects of administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was studied in 39 children with neutropenia secondary to chemotherapy (absolute neutrophil count (ANC) less than 1,500/microliters. The children were divided into two groups. The first group (G-CSF) included 25 children (12 with acute lymphoblastic leukemia [ALL]-non-Hodgkin's lymphoma [NHL] and 13 with solid tumors) and the second group (GM-CSF) included 14 children (5 with ALL-NHL and 9 with solid tumors). All 39 children received of either G-CSF or GM-CSF (5 micrograms/kg/day) subcutaneously at the end of each chemotherapy course for a maximum duration of 14 days. The effect of G-CSF and GM-CSF on the ANC, the antibiotic therapy administration, and the length of hospital stay were studied for both groups at two cycles of chemotherapy. During both cycles a faster rise of ANC was observed in the children of the first group (G-CSF) compared with those of the second group (GM-CSF), but there was no difference in either the incidence of antibiotic therapy administration between the two groups (26% vs 25%) or the length of hospitalization. Both growth factors were well tolerated by all children studied with minimal side effects observed (including bone pain with G-CSF in 2 of 25 children and pruritus with GM-CSF in 1 of 14). We conclude that G-CSF reduces the duration of neutropenia more than does GM-CSF, but the incidence of severe infection and the duration of hospitalization do not differ between children receiving either G-CSF or GM-CSF.

Administration, Cutaneous↗

Treatment with recombinant human erythropoietin in children with malignancies.

The effect of recombinant human erythropoietin (rHuEPO) on the anemia of cancer was examined in 15 children with hematologic malignancies (group I) and solid tumors (group II), whose hemoglobin (Hb) was under the third percentile for sex and age. The response to rHuEPO was defined as an increase of Hb to above the 10th percentile following 8 weeks of therapy. The rHuEPO caused an increase in the Hb and hematocrit (Hct) in 46% of children of both groups at a dose of 150 IU/L, in 28.5% of children at a dose of 250 IU/L and in 25.5% of children at a dose of 400 IU/L. Leukocyte and platelet counts were not influenced by the rHuEPO treatment. The red cell transfusion requirement decreased to 66% in both groups after rHuEPO treatment. Erythropoietin (EPO) levels were measured prior to the treatment and then every 4 weeks during rHuEPO treatment. Children who responded to EPO had an initial EPO level of < 100 IU/L, while those who did not respond had an initial EPO level of > 100 IU/L. Erythropoietin was well tolerated in all children, with no side effects.

Adolescent↗

Erythropoietin (rHuEPO) administration to premature infants for the treatment of their anemia.

In an attempt to stimulate erythrocyte production and thereby decrease the requirement for red blood transfusions, recombinant human erythropoietin (rHuEPO) was administered to 16 premature infants with birth weights less than 1000 g and to 18 with birth weights of 1000-1300 g; two corresponding groups, who did not receive rHuEPO, were used as control groups. The rHuEPO was administered subcutaneously in a dose of 300 IU/kg three times a week for 6-8 weeks. The erythropoietin decreased the red blood requirement in both groups of infants, and the increment of hemoglobin following rHuEPO administration was not statistically significant. No correlation was observed between gestational age, number of transfusions, and reticulocyte percentage. The effect of rHuEPO was higher in the group of infants with birth weights of 1000-1300 g than in those of less than 1000 g. No significant side effects were observed during rHuEPO administration.

Anemia, Neonatal↗

The expression of the ras p21 oncoprotein in the bone marrow smears of children with acute leukemia.

Point mutations of the ras genes have been detected in various hematologic malignancies. This genetic event may either occur in all malignant cells or be acquired by different subclones, which however, cannot be demonstrated adequately by analyzing only DNA derived from patient specimens. The availability of the ras p21 monoclonal antibody (MoAb) Y 13259 makes possible the direct study of the distribution of the ras gene product in human malignant cells. In this report the expression of the ras p21 oncoprotein in the bone marrow smears of 35 children with acute leukemia has been analyzed. The smears were treated with the MoAb Y 13259, biotinylated goat anti-rat IgG, streptavidin, peroxidase and stained with diaminobenzidine (DAB). The intensity of the staining was evaluated by two independent observers as negative or equivocal (-/+), moderate (+) or intense (++), by counting one thousand cells. Patients were also classified according to the percentage of the stained cells into four groups (0, I, II, III). It was found that 22/35 (63%) were (+) or (++) positive as follows: 11/21 (52%) with ALL CALLA (+), 2/2 ALL-B, 3/3 ALL-T and 6/9 AML. In Group 0 (none of the blasts was stained) were 13/35 (37%), as well as in Group I (1 to 25% of the blasts stained 1+ or 2+ positive), while in Group II (26 to 50% positive stained) 3/35 and in Group III (more than 51% stained) 6/35, all of which were AML (6/9). It is concluded that the immunohistochemical analysis of the ras p21 in blast cells of children with acute leukemia may demonstrate that ras gene expression in some subclones, the intensity and percentage of which may be of some clinical importance.

Acute Disease↗

Analysis of immunohistochemical results of the ras oncogene product p21 in myelodysplastic syndromes.

Mutation of the ras oncogenes is the most commonly detected molecular abnormality in acute myelogenous leukemia and myelodysplastic syndromes (MDS). This molecular event may either be acquired by different subclones or by all malignant cells. The availability of the ras p21 monoclonal antibody Y13 259 makes possible the direct study of the distribution of the ras gene product in human malignant cells. The bone marrow smears from 41 patients with MDS were analysed by two independent observers after treatment with MoAb Y13 259, biotinylated goat antirat IgG, streptavidin, peroxidase and staining with diaminobenzidine. A high proportion of strongly positive smears was found among patients with MDS. This positivity was found in 25% of refractory anemia, in 80% of the refractory anemias with excess of blasts, and in 90% of those in transformation, while all 7 cases with chronic myelomonocytic leukemia were found positive. The percentage of positivity may suggest that activation of ras oncogene in associated with disease progression.

Adult↗

The expression of myc and ras oncogene protein in childhood lymphomas.

Paraffin sections from 21 cases of Hodgkin's disease (HD), 18 cases of non-Hodgkin's lymphomas (NHL) and 15 cases of reactive lymphadenitides occurring in children 3-15 years old were examined by immunohistochemistry for the presence of c-myc and pan-ras oncogene products. In all cases of childhood lymphomas studied c-myc protein was expressed. The highest percentage was in HD where in 29% of cases the percentage of positive cells was greater than 20%, while in only 6% of NHL cases this percentage was noted. In all cases of reactive lymphadenitides the number of cells where c-myc was expressed was less than 5%. The ras oncogene was also found in HD but with a lesser degree of positivity than c-myc. In 48% of these cases the number of positive cells ranged between 2 and 10%, while in NHL and in reactive lymphadenitides there was no positivity. The above results indicate a frequent expression of c-myc protein in childhood lymphomas. This could reflect either an implication of c-myc oncogene in the pathogenesis of these tumor or an epiphenomenon of lymphomagenesis reflecting the proliferation rate of tumor cell population. Molecular biology studies are needed to clarify this issue.

Adolescent↗