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A D'Emilio

Publications and source records attributed to A D'Emilio.

At least 19 recordsLinked to original sources

Melatonin reduces early changes in intramitochondrial cardiolipin during apoptosis in U937 cell line.

Cardiolipin (CL) is found exclusively in the inner mitochondrial membrane. CL deficiency leads to an alteration in the stability of mitochondrial membranes, to an increased permeability as well as a decreased respiratory rate, and therefore to mitochondria which are completely dysfunctional. It is known that reactive oxygen species (ROS) cause a decrease and a variation in CL content, concomitantly the formation of the mitochondrial permeability transition pore facilitates the release of cytochrome c (cyt c) into the cytosol. Melatonin (Mel), the secretory product of the pineal gland, is a potent and efficient endogenous radical scavenger. It has been shown to protect, various biomolecules, such as DNA, membrane lipids, and cytosolic proteins from oxidative damage. To evaluate the protective role of Mel, we have studied U937 cells treated with UV-B irradiation. In our model, the administration of 1mM Mel before UV-B irradiation showed a significant protection from apoptotic cell death, in particular, mitochondrial structure and function were preserved through apoptotic pathways when cells were preincubated with 1mM Mel before UV-B exposure. The cardiolipin-sensitive probe 10-nonyl acridine orange (NAO) was used to monitor changes in mitochondrial lipids. Our data suggest that the Mel treatment protects CL from ROS and this suggests a possible link with the reduction of the apoptotic phenomenon.

Apoptosis↗

Epidemiological analysis of vancomycin-resistant enterococci in a large tertiary-care hospital in Northern Italy.

The epidemiology of vancomycin-resistant enterococci (VRE) was studied in a large tertiary-care hospital in northern Italy from February 1993 to December 1999. Sixteen cases of bacteraemic and 17 cases of nonbacteraemic active infections caused by VRE were recorded. Fifteen of the bacteraemic and four of the nonbacteraemic infections occurred in patients in the haematology department, while the remainder were registered in other departments of the same hospital. Active surveillance for the presence of VRE in stools led to identification of 51 noninfected carriers over the 1994-1999 period; of these, 32 were haematology patients and the remainder were patients admitted to other departments. All VRE isolates carried the vanA gene. Forty-one Enterococcus faecium isolates and eight Enterococcus faecalis isolates collected in the 1993-1996 period were typed by pulsed-field gel electrophoresis. Twenty-nine isolates of Enterococcus faecium shared either indistinguishable or strictly or possibly related patterns. Of these, 26 were isolated from patients in the haematology department. This is believed to be the first study on the epidemiology of VRE carried out in a large hospital in Italy over a period of several consecutive years. It reports an increase in VRE due to the epidemic spread of genetically related strains and sporadic infections or colonisation by unrelated VRE. It also documents the success of surveillance and of the measures adopted for preventing the spread of VRE in patients at risk.

Bacteremia↗

Induction-consolidation with an idarubicin-containing regimen, unpurged marrow autograft, and post-graft chemotherapy in adult acute lymphoblastic leukaemia.

Between 1991 and 1993 we conducted a collaborative trial in adult acute lymphoblastic leukaemia, introducing an idarubicin (IDA)-containing regimen for induction and early consolidation, and increasing consolidation intensity with an autologous bone marrow transplantation phase (ABMT, patients aged <51 years) followed by further chemotherapy for 12 weeks and low-dose maintenance for 6 months (ABMT patients) or 18 months. 96 patients were evaluable for antileukaemic response after induction with vincristine-prednisone-L-asparaginase plus cumulative IDA 36 or 20 mg/m2 (IVAP-1 and IVAP-2), and for disease-free survival (DFS) after a minimum follow-up >3.5 years with an off-therapy interval >1.5 years. The response rate was 44% (7/16) with IVAP-1 and 90% (72/80) with IVAP-2 (P=0.0001), due to regimen-related toxicities. Post-remission therapy was administered as planned to most cases but protocol violation was registered in some patients eligible to ABMT and post-graft chemotherapy. The 5-year disease-free survival (DFS) rate was 31%. Multivariate analysis indicated that DFS was improved in patients receiving a transplant (11 allogeneic, DFS 70%; 32 ABMT, 36%; 37 neither, 17%; P < 0.001) and was negatively affected by high-risk features such as blast cell count >25x10(9)/l, T-cell or mature B-cell immunophenotype, and t(9;22)/t(4;11) (all P values <0.05). The 5-year DFS rate was 54% for 26 patients with no high-risk factor, 26% for 35 patients with any one, and 6% for 18 patients with any two (P<0.005). IVAP-2 brought about a high complete response rate and post-remission treatment including ABMT was feasible and modestly toxic. In spite of the short post-graft chemotherapy phase, the long-term DFS rate was good in cases with no high-risk feature. However, because autografting may be redundant in the standard-risk category, its role requires further investigation for high-risk cases.

Adolescent↗

Age-adapted moderate-dose induction and flexible outpatient postremission therapy for elderly patients with acute lymphoblastic leukemia.

We report the results of a recent trial in elderly acute lymphoblastic leukemia (ALL) patients (> or = 60 years). Initial chemotherapy consisted of one 14-day course with single-dose idarubicin plus vincristine-prednisone-L-asparaginase. Idarubicin was preferred to other anthracyclines because of its shorter time to response. Sequential outpatient postremission therapy included single-dose idarubicin plus vincristine-cyclophosphamide-L-asparaginase pulses, cranial irradiation with intrathecal methotrexate-cytarabine, flexible weekly vincristine-cyclophosphamide alternating with cytarabine-teniposide, and two-year standard maintenance with mercaptopurine-methotrexate. Granulocyte colony-stimulating factor (G-CSF) was added to induction and early consolidation courses. Twenty-two patients mainly with high-risk features entered the study: median age was 64 years (60-73), 40% of cases were CD10- B-lineage and T-lineage ALL, 38% of CD10+ B-lineage ALL carried a BCR-ABL rearrangement, while 23% coexpressed myeloid antigen, 86% had L2 morphology, 50% had a blast count greater than 10 x 10(9)/1, 54% had hepato-splenomegaly and lymphadenopathy. The complete remission (CR) rate after induction therapy was 59%. A partial remission was obtained in two cases. There were four early deaths (18%) and three refractory ALL (14%). Median time to response was 21 days. With G-CSF, the median duration of absolute neutropenia was 10.5 days. Flexible postremission therapy was very well tolerated, causing no major toxicity. With a median follow-up of 2.6 years, 3 patients remain alive in first CR (23%), 2 of whom at 21.3 months and 39.6 months, respectively. Median survival of responders was 12 months compared to only 1.2 months for nonresponders (p < 0.001). This moderate-dose idarubicin-containing and G-CSF-supported regimen was associated with a high early remission rate in elderly ALL. Postremission therapy results were modest, though not appreciably different from the general experience in this patient population. Because further escalation of drug intensity appears unjustified, attempts to document and reverse drug resistance patterns and restore a dysregulated apoptosis must be considered.

Aged↗

Idarubicin in the initial treatment of adults with acute lymphoblastic leukemia: the effect of drug schedule on outcome.

Fifty two adults (aged 15 to 66 years) with newly diagnosed acute lymphoblastic leukemia (ALL, n = 47) or lymphoid blast phase chronic myelogenous leukemia (Ly-CML, n = 5) were managed with three distinct protocols containing idarubicin at a cumulative dose of 36, 20, and 10 mg/m2, respectively, plus vincristine, L-asparaginase, and prednisolone (IVAP-1, -2, -3). IVAP-1 was highly toxic and gave a low complete remission (CR) rate (7/17, 41%). Nine patients died of complications while severely neutropenic, and one had resistant disease. In contrast, 24 of 28 patients subsequently treated with IVAP-2 achieved a CR (86%, p 0.005), the rate of both hematological and extrahematological toxicity being significantly reduced compared with IVAP-1 (p < 0.05). With IVAP-3, 6/7 patients aged > 60 years achieved CR. IVAP-2 with total idarubicin 20 mg/m2 is a very effective and well tolerated regimen for the initial treatment of adults with ALL.

Adolescent↗

Intensive therapy for adult acute lymphoblastic leukemia: preliminary results of the idarubicin/vincristine/L-asparaginase/prednisolone regimen.

Between June 1991 and September 1992, 80 patients with adult acute lymphoblastic leukemia (ALL) (newly diagnosed, n = 68; relapsed or refractory ALL, n = 7; lymphoid blast transformation of Philadelphia chromosome-positive chronic myelogenous leukemia [LT-CML], n = 5) were managed with a combination regimen consisting of idarubicin 36, 20, or 10 mg/m2 plus vincristine, L-asparaginase, and prednisolone (IVAP-1, -2, -3). Three patients with LT-CML and four with relapsing ALL had a complete remission. In the group of newly diagnosed patients aged 15 to 60 years treated with IVAP-1, the complete remission rate was only 44% due to the high incidence of toxic deaths. In contrast, 39 of 44 cases who subsequently received IVAP-2 achieved a complete remission (89%, P = .001), as did 62% of elderly patients who received IVAP-3. Hematologic and nonhematologic toxicity was significantly reduced with IVAP-2 compared with IVAP-1. The use of recombinant human granulocyte colony-stimulating factor in 24 patients was not associated with a reduced duration of granulocytopenia less than 0.5 x 10(9)/L, although there was a lower incidence of documented infections in patients receiving granulocyte colony-stimulating factor than in controls. Post-remission intensification with idarubicin-based courses, high-dose therapy with autologous bone marrow stem cell rescue, and rotational weekly therapy was feasible and its toxicity was manageable. These preliminary findings indicate that IVAP-2 (idarubicin 20 mg/m2) is a highly effective and well-tolerated regimen for remission induction of adult ALL.

Adolescent↗

Treatment of adult acute lymphoblastic leukaemia (ALL) over a 16 year period.

Between 1972 and 1988 269 newly diagnosed adolescents and adults (age range 14-78 years) with ALL were managed with three protocols of increasing intensity (OPAL, HEAV'D, OPAL-HDAraC). The complete remission (CR) rate in 212 patients treated with OPAL and HEAV'D was 151/212 (71%), the median CR duration was 1.9 years. With a median follow-up of 9 years, 49 patients remain free of disease. On multivariate analysis age, blast cell count, and immunophenotype were found to correlate significantly with CR rate, remission duration and survival. CR was achieved in 38/57 (67%) patients subsequently treated with OPAL-HDAraC; however, although remission duration was longer in 'high risk' patients (T, B and Null phenotype irrespective of blast cout, cALLA+ve with blast count greater than 10 x 10(9)/l) as compared to the results achieved in similar patients with OPAL/HEAV'D, overall, the results were no better than those achieved previously. Indeed, patients in the 'standard risk' category (cALLA+ve, blast count less than 10 x 10(9)/l) fared better previously. Subsequently, neither treatment according to prognostic variables, or the addition of different pairs of drugs in rotation, to HEAV'D, have improved outcome in 63 other patients. Currently, further intensification of the early treatment is being evaluated.

Adolescent↗

Long-term results of the HEAVD protocol for adult acute lymphoblastic leukaemia.

Between 1979 and 1987, 82 adults (age 14-71 years) with acute lymphoblastic leukaemia (ALL) were treated with a 6-course protocol called HEAVD, the main feature of which was the early postremission administration of escalating doses of doxorubicin (total 405 mg/m2) and cyclophosphamide (total 2.5 g/m2). A complete remission (CR) was attained in 66 patients (80%, 95% confidence intervals, [CI] 71%-89%). Factors affecting favourable CR achievement were age less than 60 years and absence of lymphadenopathy-hepatosplenomegaly at presentation (P less than 0.05). Median duration of CR was 27 months. 26 patients remain in first continuous and unmaintained CR, 18 of whom between 5.9 and 11.1 years, for an estimated 39% prolonged disease-free survival (95% CI 27%-51%). CR duration correlated significantly with absolute blast cell count (15 x 10(9)/l or less compared to more) and age (30 years or under compared to over). Overall, 29 patients are alive with a median follow-up of 6.7 years, the projected long term survival being 35% at 11 years (95% CI 24%-46%). Treatment-related toxicity included 1 lethal case of L-asparaginase-related thromboembolism and 3 toxic deaths among 66 CR patients. Late-onset toxicity was not observed in long-term survivors. The relatively late occurrence of endpoint events (relapse and death) in adult ALL confirms that long-term updating is necessary to determine the curative potential of modern chemotherapy programs for the disease.

Adolescent↗

Incidence and risk factors for thrombotic complications in a historical cohort of 100 patients with essential thrombocythemia.

The purpose of this study was to determine which factors were associated with an increased risk of thrombo-hemorrhagic complications in a historical cohort of 100 consecutive and unselected patients with essential thrombocythemia (ET) in whom busulfan treatment was given when platelets were more than 1,000 x 10(9)/L and/or a major thrombotic or hemorrhagic event occurred. The incidence of major hemorrhagic complications was very low (0.33%/person-time at risk [pt-yr]) in comparison with that of thrombotic episodes (6.6%/pt-yr). In an adequate and appropriate control historical group of 200 patients, no severe hemorrhages were recorded and the incidence of thrombotic events was 1.2% pt-yr. Thus, the analysis of risk factors was restricted to this latter group of events. Age, a previous thrombotic event, and long duration of thrombocytosis were identified as major risk factors for thrombosis, while smoking, diabetes mellitus, hyperlipidemia, and hypertension did not influence the rate of thrombotic episodes.

Adolescent↗

Circadian time structure of pituitary and adrenal response to CRF, TRH and LHRH.

In six healthy males, aged 25.3 +/- 0.66, the pituitary and adrenal simultaneous response to CRF (1 microgram/kg), TRH (200 micrograms) and LH-RH (100 micrograms) was studied at the following times of different days: 0400, 0800, 1200, 1600, 2000 and 0000. Each test was preceded by a 8-hr fast after a meal containing 600 cal (CHO 50%, lipid 30%, protein 20%). The interval between two consecutive tests was 52 hrs and the starting time was randomized. The serum cortisol was measured before and after 60, 120, 180, 240 min. Serum TSH, Prolactin, FSH and LH were measured before and after 5, 10, 15, 30, 60, 90 and 120 min. The statistical analysis was reported by both mean chronograms (as absolute values and relative change or absolute difference from mesor) and mean cosinor on basal values and total (T.A.) or incremental (I.A.) areas after RH stimulus. Serum cortisol: a statistically significant circadian rhythm was found for basal values with a peak in the morning (phi at 1040; 95% C.L. 0808-1438). T.A. after RH stimulus as well appeared statistically higher again in the morning, whereas the I.A. presented an opposite phase with higher values at night (phi at 2133; 95% C.L. 2055-0312). Serum Prolactin: mean chronogram analysis showed significantly higher basal values at 0800 and lower values at 1600, whereas I.A. were significantly lower in the morning. Serum LH: basal values were statistically higher in the morning, while T.A. and I.A. showed an opposite behaviour with peaks in the night (T.A.: phi at 2015, 95% C.L. 1710-0035; I.A.: 0 2033; 95% C.L. 1736-0004).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Cytogenetic and clinical studies in acute promyelocytic leukemia (M3) and cytologic M3 variant (M3V).

Cytogenetic specimens were obtained from bone marrow 24-hour cultured cells in 22 patients with acute promyelocytic leukemia, including six with microgranular variant. A t(15;17) was identified in 10-100% of metaphase cells from 13 patients. We have found no correlation between complete remission percentage and karyotype. Our data suggest that each laboratory, as far as M3 and M3V are concerned, must study its own culture time as it relates to numerous parameters involving tumoral cell kinetics.

Adolescent↗

Preliminary observations on intravenous idarubicin (4-demethoxydaunorubicin) in the chronic and accelerated phase of chronic myelogenous leukemia.

The study included 13 patients with chronic myelogenous leukemia (8 in the chronic phase with high WBC counts at onset, and 5 in the accelerated phase, poorly responding to conventional drugs for the chronic phase). They were treated with 4-demethoxydaunorubicin (idarubicin), a new anthracycline analog more active than daunorubicin (DNR) and doxorubicin (DX) in experimental tumor models which offers a higher therapeutic index than existing anthracyclines. Idarubicin was administered i.v. at the dose of 8 mg/m2 on days 1, 3 and 5. All patients in the chronic phase (8/8) developed significant leukopenia. Five of these 8 patients showed complete reduction of splenomegaly, and 4 of hepatomegaly as well. In all the other cases, hepato-splenomegaly was reduced by more than 70%. Three of the 5 patients in the accelerated phase of chronic myelogenous leukemia also showed massive cytolysis. More important, all of them showed complete or major reduction of hepato-splenomegaly and renewed responsiveness to conventional drugs for the chronic phase of the disease. Idarubicin was fairly well tolerated by all patients with only minor gastrointestinal side effects and no liver damage or acute cardiotoxic effects. These findings indicate that idarubicin--although it cannot replace established drugs for the chronic phase of the disease--represents an added therapeutic resource for producing rapid cytolysis at onset and, above all, in the accelerated phase of chronic myelogenous leukemia.

Administration, Oral↗

Platelet dysfunction in splenectomized patients with hairy cell leukemia.

Platelet function was assessed in 17 patients with hairy cell leukemia who had undergone splenectomy. Defective PAF-induced aggregation and selective reduction of beta-thromboglobulin were found in platelets from six and eight patients respectively. These defects were not necessarily associated with bleeding complications.

Adult↗

[Diverticular aneurysm of the right atrium].

A case of right atrium aneurysm (diverticulum) detected in an asymptomatic 61-year-old woman is described. Diagnosis was made according to echocardiographic and echocontrastographic findings and was confirmed by both angiographic data and surgical pathology. The rarity of this finding and the possibility of a correct non-invasive assessment can be considered the two most peculiar features of this case.

Angiocardiography↗

Bleeding on patients with autoimmune thrombocytopenic purpura and normal platelet count.

80% of patients with chronic autoimmune thrombocytopenic purpura (ATP) may reach normalization of platelet count after steroids or splenectomy. In some of these cases a bleeding tendency may still persist and this has been attributed to abnormalities of platelet function resulting from the effect of platelet-bound antibodies. We have studied 49 ATP patients in order to assess the frequency and the pattern of this immune thrombopathia, and the correlation with the levels of platelet associated IgG (PAIgG). Only 3 patients (6%) had prolonged bleeding time and persistence of mucocutaneous haemorrhages, whereas 36% presented an altered platelet aggregation pattern. Platelet serotonin content, platelet and plasma beta-thromboglobulin concentration, and malondialdehyde generation after thrombin stimulus were found also altered, but the findings were not clearly correlated with the concentration of PAIgG.

Adolescent↗

Treatment of 49 unrandomized patients with advanced Hodgkin's disease.

Forty-nine patients with previously untreated advanced Hodgkin's disease were treated in our Institution between 1973 and 1981. Treatment modalities of these patients were reviewed, and they were divided into 3 groups according to the treatment employed: 13 patients received MOPP only, 22 patients received MOPP plus involved field radiotherapy, and 14 received alternating MOPP/ABVD chemotherapy. The response rates for the 3 groups were respectively 38.5%, 63.6% and 78.6%. A longer follow-up is needed to assess a significant difference in survival curves. The advantages of adjuvant radiotherapy and alternating non-cross-resistant drugs in advanced Hodgkin's disease are discussed.

Adolescent↗