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Biomedical subjects

L Canepa

Publications and source records attributed to L Canepa.

32 records · Page 2Linked to original sources
PubMed1989

Catalase and glutathione peroxidase are equally active in detoxification of hydrogen peroxide in human erythrocytes.

Genetic deficiencies of glucose-6-phosphate dehydrogenase (G6PD) and NADPH predispose affected erythrocytes to destruction from peroxides. Conversely, genetic deficiencies of catalase do not predispose affected erythrocytes to peroxide-induced destruction. These observations have served to strengthen the assumption that the NADPH/glutathione/glutathione peroxidase pathway is the principal means for disposal of H2O2 in human erythrocytes. Recently, however, mammalian catalase was found to have tightly bound NADPH and to require NADPH for the prevention and reversal of inactivation by its toxic substrate (H2O2). Since both catalase and the glutathione pathway are dependent on NADPH for function, this finding raises the possibility that both mechanisms destroy H2O2 in human erythrocytes. A comparison of normal and acatalasemic erythrocytes in the present study indicated that catalase accounts for more than half of the destruction of H2O2 when H2O2 is generated at a rate comparable to that which leads to hemolysis in G6PD- deficient erythrocytes.

Carbon Dioxide↗
PubMed1987

A case of ataxia telangiectasia with unbalanced glucose 6-phosphate dehydrogenase mosaicism in the granulocytic/monocytic lineages.

Ataxia telangiectasia is a genetically determined disease with multi-system abnormalities and a high incidence of neoplasia. In order to define the nature of the association between ataxia telangiectasia and malignancy, we investigated a patient with the disease and heterozygote for the Mediterranean variant of the X-linked marker glucose 6-phosphate dehydrogenase. Enzymatic mosaicism in hemopoietic and nonhemopoietic cells was evaluated with the 2-deoxy glucose 6-phosphate technique. While erythrocytes, platelets, and lymphocytes expressed the same double-enzyme phenotype as tissues of nonhemopoietic origin, granulocytes and monocytes expressed almost exclusively the Mediterranean-type enzyme. We suggest that, as the result of genetic instability at the hemopoietic stem-cell level, the granulocytic/monocytic progeny enjoyed a proliferative advantage and became the predominant clone.

Ataxia Telangiectasia↗
PubMed1985

Clonal development from a progenitor with restricted differentiative expression in acute lymphoblastic leukemia.

Three patients with acute lymphoblastic leukemia (ALL) and heterozygous for the Mediterranean variant of glucose-6-phosphate dehydrogenase (G6PD) have been investigated with the 2-deoxyglucose-6-phosphate (2dG6P) method to determine the number and type of progenitor cells in which the disease arose. A monoclonal origin was established for the lymphoblasts, while the other hemopoietic cell lines were not involved in the leukemic process.

Child↗
PubMed1984

Clonal origin of cells restricted to monocytic differentiation in acute nonlymphocytic leukemia.

Two patients with acute monocytic leukemia and heterozygous for the Mediterranean variant of the X-linked enzyme, glucose-6-phosphate dehydrogenase (G6PD), were investigated to determine the number and type of progenitor cells involved. Mosaicism for Mediterranean G6PD was assessed by the different rate of utilization of 2-deoxy glucose-6-phosphate (2dG6P) by normal and Mediterranean variants of G6PD. The monocytoid blasts were found to express one type of G6PD only, indicating their clonal origin from a common progenitor cell, whereas all other hemopoietic cell populations tested expressed the heterozygous phenotype. The finding of a unique involvement of the monocytic line in two cases of acute nonlymphocytic leukemia (ANLL) represents further evidence of heterogeneity of stem cell involvement in ANLL.

Cell Differentiation↗
PubMed1983

Reexpression of normal stem cells in erythroleukemia during remission.

A patient with erythroleukemia and heterozygous for the Mediterranean variant of the X-linked enzyme glucose-6-phosphate dehydrogenase (G6PD) was studied to determine the number and type of progenitor cells in which the disease arose. G6PD mosaicism was assessed by the different rate of utilization of 2-deoxy-glucose-6-phosphate (2dG6P) by normal and Mediterranean variants of G6PD. Erythroleukemia is established as a clonal disease involving a precursor cell common to the erythroid and myeloid lines. After intensive chemotherapy, restoration of nonmonoclonal hemopoiesis is achieved, as indicated by the reappearance of the mosaic phenotype in hemopoietic cell populations.

Aged↗
PubMed1982

Primary thrombocythemia: clonal origin of platelets, erythrocytes, and granulocytes in a GdB/GdMediterranean subject.

A patient with primary thrombocythemia, who was heterozygous for glucose-6-phosphate dehydrogenase deficiency (GdB/GdMed), was investigated to test for the clonal origin of this myeloproliferative disorder. In order to assess somatic cell mosaicism in various tissues, we have made use of the different rate of utilization of 2-deoxyglucose-6-phosphate, an analog of glucose-6-phosphate, by normal glucose-6-phosphate dehydrogenase and by the Mediterranean variant: the results demonstrate that essential thrombocythemia is a clonal disease involving the erythrocytic, granulocytic, and megakaryocytic series, without affecting monocytes, T lymphocytes, and non-T lymphocytes.

Aged↗
PubMed1981

Marked karyotype abnormalities in two cases of acute myelogenous leukemia.

Two patients with acute myelogenous leukemia with severe chromosome abnormalities are described. The cytogenetic analysis shows the following karyotype: patient No. 1: 41,XY,-1,-2,-4,-5,-13,-15,-17,-18,-22,+5 markers; patient No. 2: 46,XY,-2,-5,-7,-13,+16,-21,-21,+5 markers. In each patient one set of double minute chromosomes was observed.

Aged↗
PubMed1981

Urinary granulopoietic activity in chronic myelogenous leukemia: follow-up and correlation with various phases of the disease.

Daily urinary colony-stimulating factor (CSF) output was tested in 16 patients with chronic myeloid leukemia, 12 of which were in stable phase and 4 in blast crisis of the disease. The CSF of stable-phase patients varied within normal range, while all patients in blast crisis had values lower than normal. Also the number of CFUC ranged within normal values in stable-phase patients, while no colony growth was detectable in blast-crisis patients. Sequential studies (28 or 11 months) of 2 patients revealed an inverse relation between daily urinary CSF and presence of peripheral immature or blast cells in the patient in stable or blast phase, respectively.

Adult↗
PubMedDate not supplied

Feprazone: absence of hemolytic effects in glucose-6-phosphate dehydrogenase-deficient subjects.

Some drugs, including nonsteroidal antiinflammatory compounds, can be hemolytic in glucose-6-phosphate dehydrogenase-deficient patients. We have studied the potential hemolytic activity of feprazone, a nonsteroidal antiinflammatory compound in vitro and in vivo. Agents that may be hemolytic for glucose-6-phosphate dehydrogenase-deficient erythrocytes will stimulate the hexose monophosphate shunt in normal erythrocytes. Eleven normal subjects were treated with feprazone and their erythrocytes were incubated in their own sera (containing active feprazone metabolites) and [1-14C]-glucose. Because no statistically significant increase in 14CO2 evolution was observed, 15 pediatric male patients with glucose-6-phosphate dehydrogenase deficiency who required antiinflammatory treatment were treated with feprazone. No hemolytic crises and no statistically significant changes of hematologic tests were observed.

Adolescent↗
PubMedDate not supplied

Fludarabine in untreated and previously treated B-CLL patients: a report on efficacy and toxicity.

BACKGROUND: It has been shown that fludarabine (FLU) is superior to conventional treatment in B-CLL for rate and quality of response, leading to CR even at the molecular level. In this paper we report our preliminary results with this drug in B-CLL patients. METHODS AND PATIENTS: Twenty-seven B-CLL patients (16 refractory to previous therapy, 7 responsive and treated for subsequent disease reexpansion, 4 untreated with active disease) were administered FLU at a dose of 25 mg/sqm for 5 days every 4 weeks. RESULTS: Twenty-five patients were evaluable and 14 of them (56%) were responsive. All four untreated patients responded: 1 CR (PCR analysis showed the persistence of clonal VDJ rearrangement) and 3 PR, while 67% of the previously responsive group again showed a reaction: 2 PR (33%) and 2 nodular PR (33%). Among the refractory patients we recorded 6 responses (39%): 1 CR (6%) and 5 PR (33%). Besides 2 cases of lethal myelotoxicity, we observed 2 cases of encephalopathy and 2 cases of heart failure. Four deaths may have been related to FLU therapy (15%). CONCLUSIONS: We confirm the effectiveness of FLU and the improved outcome, in terms of toxicity and response rate, it provides in untreated B-CLL patients. Further studies are needed to explore the possible negative effects of FLU on neuronal and heart function, and the impact of this drug on survival in selected groups of patients.

Adult↗
PubMedDate not supplied

An unusual reaction to alpha interferon in a case of non Hodgkin's lymphoma.

A 64-year-old man suffering from non Hodgkin's lymphoma in progression and resistant to conventional chemotherapy was treated with alpha interferon. In a few days he developed an unusual adverse reaction characterized by severe dermatological and neuromuscular toxicity. We describe the case and suggest a possible pathogenetic mechanism for this rare event.

Drug Eruptions↗
PubMedDate not supplied

High efficacy of fludarabine-containing therapy (FLAG-FLANG) in poor risk acute myeloid leukemia.

BACKGROUND: Elderly patients with acute myeloid leukemia (AML) those refractory to induction chemotherapy and those with so-called secondary leukemia have unfavorable prognoses and require innovative therapeutic approaches. Fludarabine allows an increased accumulation of Ara-CTP in leukemic cells and inhibits DNA repair mechanisms; therefore its association with Ara-C and mitoxantrone results in a synergistic effect. MATERIALS AND METHODS: From May 1993 to February 1996, fludarabine-containing regimens (FLAG and FLANG) were employed as induction therapy in 51 high-risk AML patients. Diagnosis of AML in 22 patients was preceded by a myelodysplastic syndrome lasting more than six months; 8 of the 29 de novo AML cases (28%) were refractory to previous chemotherapy, 9 (31%) were treated for early relapse, 12 (41%) presented poor prognostic factors at diagnosis. The median age was 64 (range 33-76) years and the FAB subtypes were the following: M0 3, M1 5, M2 28, M4 7, M5 8. Forty-eight per cent of patients showed poor prognosis chromosomal abnormalities. FLAG (24 patients) consisted of both fludarabine 30 mg/sqm over 30 minutes followed 4 hours later by Ara-C 2 g/sqm over 4 hours (for 5 days) and G-CSF 300 micrograms/day administered 12 hours before fludarabine, for a total of 5 doses. FLANG (27 patients) had a shorter duration (3 days), reduced Ara-C dosage (1 g/sqm) and administration of mitoxantrone (10 mg/sqm) at the end of Ara-C infusion. RESULTS: Recovery of both neutrophils (PMN > 0.5 x 10(9)/L) and platelets (Plt > 20 x 10(9)/L) required a median of 16 days from the end of therapy. Overall, 30 patients (59%) achieved CR, 6 (11%) PR and 10 (20%) were refractory; 5 (10%) experienced early death (cerebral hemorrhage or infection). The length of complete response ranged from 2 to 26 months with a median follow-up of 8 months. De novo and secondary AML registered 62 and 54% CR rates, respectively. Eight out of 10 patients refractory to conventional schemes achieved CR (80%) but only 3 out of 10 treated for relapse obtained CR (30%). CONCLUSIONS: FLAG and FLANG showed similar activity and toxicity while proving to be highly effective and relatively well-tolerated treatments for high-risk de novo AML. Secondary leukemias seemed to be responsive as well, but the presence of an unfavorable karyotype alteration lowered the response rate.

Acute Disease↗