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Biomedical subjects

G Papa

Publications and source records attributed to G Papa.

At least 55 records · Page 3Linked to original sources
PubMed1995

Lineage identification of acute leukemias: relevance of immunologic and ultrastructural techniques.

This study assesses the value of immunologic and ultrastructural methods in disclosing the lineage commitment of cells from acute leukemias (ALs). Two hundred and fifty-one ALs were characterized morphologically, cytochemically, and immunologically. Myeloperoxidase (MPO) positivity in > 3% of blasts was regarded as evidence of the myeloid origin of leukemic cells, cytoplasmic CD22 (cCD22) expression was taken as an indication for B-lineage acute lymphoblastic leukemia (ALL), and CD3+ (membrane or cytoplasmic) cases were classified as T-ALL. Diagnosis of minimally differentiated acute myeloid leukemia (AML-M0) was made when blast cells had undifferentiated features by light microscopy, reacted with at least one of the antibodies to myeloid-specific antigens (CD13, CD33, MPO), and lacked CD19, cCD22, and c/mCD3. Megakaryoblastic differentiation was demonstrated by the expression of CD41 and/or CD61. Following these criteria, 209 cases were classified as acute myeloid leukemia (AML) and 39 as ALL. Expression of lymphoid antigens was detected in 45% of AML cases and 30% of ALLs showed myeloid antigens. One case was regarded as a true biphenotypic leukemia because of the combined expression of MPO and CD33 for the myeloid lineage, and cCD3, CD2, and CD5 for the T-cell lineage. Two cases lacked signs of myeloid or lymphoid differentiation and were studied by electron microscopy methods. One displayed platelet peroxidase (PPO) activity and was classified as a megakaryoblastic variant, one other reacted with anti-CD33 and was considered AML-M0. We conclude that light microscopy and standard immunologic methods can accurately demonstrate the lineage orientation in greater than 99% of ALs. Integration with ultrastructural analysis can define the cell nature of virtually all cases of AL.

Adolescent↗
PubMed1995

[Peripheral stem cells: from biology to therapy].

The tumor cells' response to more aggressive treatment has been shown in many different malignancies with various drugs, as alkylating agents, antimetabolites and anthracyclines. The use of high-dose chemotherapy is limited by especially haematological toxicity. Autologous stem cell transplantation (ASCT) is now used to prevent or decrease haematological toxicity induced by intensive chemotherapy. Stem cells can be harvested using bone marrow or peripheral blood. In both cases recombinant human growth factors (G-CSF, GM-CSF, IL3) have been administrated to decrease marrow aplasia duration after transplant. Peripheral blood stem cell autograft seems to be the first transplantation technique in patients with bone marrow hypocellularity induced by previous irradiation and/or neoplastic involvement.

Female↗
PubMed1995

[Antiphospholipid antibodies: their prevalence, clinical significance and correlation with cytokine levels in acute myeloid leukemia and non-Hodgkin's lymphoma].

Forty-five patients with de novo acute myeloid leukemia (AML) and 22 patients with newly-diagnosed non-Hodgkin lymphoma (NHL) were investigated. Tests for antiphospholipid antibodies (APA) included the measurement of anticardiolipin antibodies (aCL) with a solid-phase immunoassay, and the detection of the lupus-like anticoagulant (LA) activity. Fifteen patients with AML (33.3%) and 9 patients with non-Hodgkin lymphoma (40.9%) presented elevated APA at diagnosis, as compared to 3 out of 174 persons of the control group (p < 0.0001). APA titles became normal in all patients responding to treatment, whereas non-responders retained elevated levels. In addition, 2 patients (1 with AML and 1 with NHL) who had normal APA at diagnosis and were either refractory to treatment or in relapse, subsequently developed LA and/or aCL positivity. At presentation, the mean levels of IgG- and IgM-aCL in patients were not significantly different from controls, and concordance between aCL and LA results reached just 12%. With regard to the clinical course, we were not able to detect any statistically significant difference between patients with normal and elevated APA. Pretreatment concentrations of IL-6 and TNF-alpha in AML, and soluble form of the receptor for interleukin-2 (sIL-2r) in NHL were found significantly elevated compared to controls (p < 0.001, p = 0.011 and p = 0.016 respectively). In addition, the levels of these cytokines correlated with IgG-aCL at the different times of laboratory investigations. These results demonstrate that APA may have a role as markers of disease activity and progression in some haematological malignancies.

Acute Disease↗
PubMed1994

Detection of soluble interleukin-2 receptor and interleukin-10 in the serum of patients with aggressive non-Hodgkin's lymphoma. Identification of a subset at high risk of treatment failure.

BACKGROUND: This study explores the ability of the combined detection of soluble IL-2 receptor (sIL-2r) and interleukin-10 (IL-10) to predict treatment failure in patients with aggressive non-Hodgkin's lymphoma (NHL) and to evaluate the modifications in cytokine measurements induced by the therapeutic administration of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF). METHODS: Serum levels of sIL-2r and IL-10 were measured serially in 93 patients with newly diagnosed aggressive NHL treated with four courses of a multiagent chemotherapy regimen. GM-CSF was administered subcutaneously in 39 of these patients from day +5 to day +18 after each chemotherapy course. RESULTS: Pretreatment levels of sIL-2r were greatly elevated in patients with NHL compared with control subjects (P < 0.001), significantly correlating with the Ann Arbor stage (P < 0.001) and beta 2-microglobulin (beta 2-m) concentrations (r = 0.552, P = 0.004). IL-10 was detected in 37 patients at diagnosis, with no correlation with clinicohematologic parameters, and was not detected in the control sample (P < 0.001). Cytokine and receptor levels progressively declined to normal ranges in responding patients, whereas they remained elevated in nonresponders. During administration of GM-CSF, the authors observed an increase of sIL-2r, whereas lower elevations were recorded for IL-10. However, on completion of the induction treatment, cytokine/receptor levels were comparable in patients with the same type of response, whether or not they had received GM-CSF. In the five patients who were investigated at relapse, the levels of sIL-2r, beta 2-m, and lactic dehydrogenase were found to be elevated. IL-10 concentrations were high in three of these patients: two already had detectable levels at presentation, whereas one tested positive only on recurrence. No single parameter was associated with response to therapy, but the combination of elevated IL-10 and sIL-2r concentrations greater than 3000 U/ml resulted in a subset of eight patients who failed induction chemotherapy (P < 0.001). In addition, six of eight patients with high IL-10 and beta 2-m concentrations greater than 3.3 mg/l had an unfavorable outcome (P = 0.003). A multivariate regression model was used to identify sIL-2r (P = 0.004) and beta 2-m (P = 0.043) as the covariates that amplified the prognostic ability of IL-10. CONCLUSIONS: sIL-2r and IL-10 measurements provide valuable information for better management of patients with NHL as markers to monitor disease activity and as prognostic indicators.

Adolescent↗
PubMed1994

Analysis of treatment failure in patients with minimally differentiated acute myeloid leukemia (AML-M0).

Reports of treatment of patients with minimally differentiated acute myeloid leukemia (AML-M0) are limited, heterogeneous, and controversial. We verified the prognosis of this subtype by analyzing the results of 189 consecutive patients with de novo AML. Fifteen cases fitting the criteria of AML-M0 were identified. No clinical features distinguished them from other patients with AML. The median age was 61 years (range 27 to 70), with a leukocyte count ranging from 0.6 to 185 x 10(9)/L. In all cases the leukemic cells expressed CD34 and reacted with at least one of the antibodies to early myeloid antigens, ie, CD13, CD33, or myeloperoxidase. Immunophenotypic analysis also showed positivity for CD7 in seven samples and the multidrug-resistance P-glycoprotein (P-170) in six. Cytogenetic analysis was abnormal in 12 of the 13 patients in whom an adequate number of mitoses could be evaluated. No single abnormality prevailed, the most common findings being trisomy 8 (three cases) and aberrations of chromosome 7 (two cases). Antileukemic treatment differed according to age, but for remission induction, all patients received a combination of cytosine arabinoside and an anthracycline or mitoxantrone. The prognosis of patients with AML-M0 was remarkably poor as compared with the other French-American-British subtypes. Whereas the overall rate of complete remission (CR) was 58% with a median survival of 63 weeks, only 6 of the 15 patients with AML-M0 achieved a CR, and the median survival of this group was 16 weeks (range 3 to 39). The major determinant of treatment failure was unresponsiveness to chemotherapy, as only one patient died of infection during the hypoplastic phase. The CR duration of responders was short, ranging from 3 to 22 weeks, and no second remissions were observed. We conclude that conventional combination chemotherapy yields disappointing results in AML-M0. The reason for this may be the convergence of various unfavorable prognostic factors, such as (1) the high incidence of cytogenetic abnormalities; (2) the lack of differentiation features and the expression of immaturity markers such as CD34 and CD7; and (3) the frequent expression of P-170. Nonconventional therapeutic approaches should be developed to alter the prognosis of this form of leukemia.

Adolescent↗
PubMed1994

Early detection of nephrotoxic effects in thalassemic patients receiving desferrioxamine therapy.

Nineteen transfusion-dependent beta-thalassemia major patients were included in the study. Six of these patients underwent chelation therapy with desferrioxamine by subcutaneous infusion (50 mg/kg/12 hr) and 13 received intravenous infusion (50 mg/kg/6 hr or 100 mg/kg/24 hr). BUN, creatinine, creatinine clearance, beta 2-microglobulin, urinary beta 2-microglobulin and urinary growth hormone excretion were evaluated during desferrioxamine treatment. Thirteen out of nineteen patients presented tubular damage indicated by increased excretion of urinary beta 2-microglobulin. 85% (11 of 13) of these patients showed more serious tubular damage, as demonstrated by concurrent increased urinary growth hormone excretion. Moreover, a positive correlation between urinary growth hormone excretion and urinary beta 2-microglobulin was observed (P < 0.05).

Administration, Cutaneous↗
PubMed1994

Prognostic value of serum IL-10 and soluble IL-2 receptor levels in aggressive non-Hodgkin's lymphoma.

We investigated the prognostic significance of interleukin-10 (IL-10) and soluble interleukin-2 receptor (sIL-2r) levels in the pretreatment serum of 105 individuals with newly-diagnosed aggressive non-Hodgkin's lymphoma (NHL). Commercially available enzyme-linked immunoassay kits were used for cytokine and receptor measurements. Detectable levels of IL-10 were found in 42 (40%) patients at diagnosis, with no correlation with clinico-haematological parameters, but in no control samples (P < 0.001). Pretreatment concentrations of sIL-2r were markedly increased in individuals with NHL when compared to controls (2614 +/- 893 U/ml v 219 +/- 65 U/ml, P < 0.001), patients with stage III/IV presenting higher values than those with stage II disease (3885 +/- 1196 U/ml v 1732 +/- 646 U/ml, P < 0.001). No single parameter was associated with the achievement of complete remission, but the combination of elevated IL-10 and of sIL-2r greater than 3000 U/ml selected a subset of patients with a high probability of failing induction therapy (P < 0.001). Life-table analysis also indicated that patients with these characteristics have a significantly shorter event-free survival. In a multivariate analysis the combination of IL-10 with sIL-2r was found to have greater predictive strength than the combination of IL-10 with beta 2-microglobulin. We conclude that IL-10 and sIL-2r measurements can be expected to improve existing methods of risk assignment in aggressive NHL.

Adult↗
PubMed1994

Erythema multiforme during GM-CSF therapy.

A 52-year-old Caucasian man treated with granulocyte-macrophage colonystimulating factor (GM-CSF) developed a cutaneous eruption on legs and ankles with clinical and histologic features of erythema multiforme. Laboratory studies indicated that the eruption occurred at the time of peripheral blood lymphocyte recovery and that it was coincidental with serum peaks of interleukin-1 (IL-1), interleukin-2 (IL-2), interleukin-6 (IL-6) and tumour necrosis factor-alpha. We postulate that GM-CSF provoked erythema multiforme in a predisposed individual as a consequence of either an inappropriate cytokine secretion or of an abnormal amplification mechanism following lymphocyte recovery.

Erythema Multiforme↗
PubMed1994

Prognostic value of cell marker analysis in de novo acute myeloid leukemia.

Clinical and cytologic characteristics were correlated to immunologic markers in 154 patients with newly diagnosed acute myeloid leukemia (AML). The panel of monoclonal antibodies (MoAbs) was selected to identify differentiation-associated antigens of both the myeloid and the lymphoid lineages (CD13, CD33, CD14, CD15, CD7, CD34, CD10, HLA-DR, CD19, CD2, CD5, TdT). The expression of multidrug resistance P-glycoprotein (P-170) was also evaluated in 117 patients. Differences in antigenic expression was observed among the various French-American-British (FAB) subgroups. HLA-DR was poorly expressed on the blasts of acute promyelocytic leukemia (M3), and was always found in FAB M5. CD34 was detectable in all M0 cases and only in one M3 (p < 0.001). Lymphoid-associated antigens were positive in 74 cases (48.1%). In particular, CD7 was found in 49 patients (31.8%), and TdT in 30 (21.3%), 15 samples displaying coexpression of these two antigens. The incidence of CD7+ cases was particularly elevated in M0 and M5 AML (p = 0.005). It significantly correlated with the expression of CD34, HLA-DR, P-170 (p < 0.001, p = 0.018 and p = 0.034 respectively), and with a leukocyte count > 50 x 10(9)/l (p = 0.038). Sixty-nine (59%) samples demonstrated P-170 positivity. Again, this phenotype was particularly expressed in the poorly differentiated forms (M5, M0 and M1) and showed significant correlation with the immaturity markers CD34, CD7 and HLA-DR (p = 0.013, p = 0.022 and p = 0.001, respectively). Expression of individual antigens correlated with prognosis. Refractoriness to first line therapy was associated with CD7 expression (p = 0.002) and P-170 (p = 0.001). The CD7 marker was also significantly associated with a very low overall survival (p < 0.001) and continuous complete remission (p < 0.001). CD14 expression also significantly predicted lower survival rates (p = 0.033). The combination (CD7+ CD14+) identified a subset of patients with a particularly adverse outcome. The prognostic value of CD7 expression, alone or in combination with other markers, was confirmed in multivariate analysis.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

[Helicopter assistance in Sicily. Peculiar aspects of a 3-year experience].

OBJECTIVE: To report our experience concerning the first aid effected by helicopter both on scene (primary rescue) and interhospital transport of already treated patients requiring a highest level of diagnosis and treatment (secondary rescue), and the peculiar aspect appeared from the analysis of the obtained results, that is the predominance of the secondary rescue on the primary one. DESIGN: Retrospective evaluation of the interventions effected from August 1990 to February 1993. SETTING: Critical care units of a University teaching Hospital. MAIN RESULTS: 2669 interventions were effected: 2082 were secondary rescues (78%) and 587 primary rescue (22%). The patients actually transported by helicopter were 2419 (M = 1702; F = 717). The leading cause of non effected interventions was the deficiency of illuminated helicopter landing area; for the primary rescue, the main cause was the distance from the scene and the transport with land vehicles. The most frequent admission were for intensive care unit, neurosurgery, cardiac-surgery and neonatology, in only three towns. Indeed, the failing of Specialized Units involves the use of helicopter in interhospital transport for long periods, and this can remove time from primary rescue. CONCLUSION: As mentioned above, the peculiar aspect of our experience is the predominance of the secondary rescue on the primary one. It can be attributed particularly to the geographic and orographical characteristics of our region, together with the organization deficiencies in the field of emergency medical services.

Adult↗
PubMed1993

A phase I safety study of doxifluridine and interferon-alpha-2a in patients with advanced neoplastic disease.

AIMS AND BACKGROUND: Doxifluridine (RO 21-9738, 5'-dFUR) is a fluoropyrimidine derivative with proven antitumor activity in different experimental models. On the basis of experimental evidence, several clinical trials have been carried out to define the optimal 5'-dFUR dose and route of administration. In general, the maximum monthly dose of 5'-dFUR was 36-38 g. According to these clinical data, we explored the feasibility of a combination of 5'-dFUR and interferon-alpha-2a (IFN-alpha-2a). The aim of the protocol was to confirm the maximum tolerated dose (MTD) of the drug in combination with a settled dose of IFN alpha 2a. METHODS: An open-label phase I study with intravenous 5'-dFUR was carried out in 12 patients with a histologically proven diagnosis of advanced gastrointestinal or breast cancer refractory to previous conventional hormone-chemotherapy. Escalating doses of 5'-dFUR were administered as a 2-h intravenous infusion, once a week for at least 4 weeks in groups of 3 patients. IFN-alpha-2a was administered as an intramuscular injection of 3 MU 3 times a week for 4 consecutive weeks. Physical and laboratory parameters were assessed at baseline and then weekly until the end of treatment. RESULTS: The treatment with 5'-dFUR was stopped at 5 g/m2, since this level corresponded to the maximum monthly dosage reported in the literature (36-38 g). No severe toxicity was recorded up to this drug level. CONCLUSIONS: The combination of 5'-dFUR plus IFN-alpha-2a was well tolerated at the level of 5 g/m2. Although the MTD was not reached, it can be stated that the dosage administered in this study could be explored in a larger trial.

Adult↗
PubMed1993

Antiphospholipid antibodies: prevalence, clinical significance and correlation to cytokine levels in acute myeloid leukemia and non-Hodgkin's lymphoma.

This study was designed to explore the prevalence and clinical significance of elevated antiphospholipid antibodies (APA) titres in patients affected by acute myeloid leukemia (AML) and high-grade non-Hodgkin's lymphoma (NHL). We also analyzed possible correlations with circulating levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and the soluble form of the receptor for interleukin-2 (sIL-2r). Nineteen patients with de novo AML and 14 patients with newly-diagnosed NHL were investigated. Tests for APA included the measurement of anticardiolipin antibodies (ACA) with a solid-phase immunoassay, and the detection of the lupus-like anticoagulant (LA) activity. Five patients with AML (26.3%) and 5 patients with NHL (35.7%) presented elevated APA at diagnosis, as compared to 3 of 174 persons of the control group (p < 0.0001). APA titres became normal in all patients responding to treatment, whereas non-responders retained elevated levels. In addition, 6 patients (4 with AML and 2 with NHL), who had normal APA at diagnosis and were either refractory to treatment or in relapse, subsequently developed LA and/or ACA positivity. At presentation, the mean levels of IgG- and IgM-ACA in patients were not significantly different from controls, and concordance between ACA and LA results reached just 30%. With regard to the clinical course, we were not able to detect any statistically significant difference between patients with normal and elevated APA. Pretreatment concentrations of IL-6 and TNF-alpha in AML, and sIL-2r in NHL were found significantly elevated compared to controls (p = 0.003, p = 0.009 and p = 0.024 respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗