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Biomedical subjects

E Pozzoli

Publications and source records attributed to E Pozzoli.

45 records · Page 3Linked to original sources

Ultrastructural alterations of megakaryocytes in some hematologic disorders.

Bone marrow and peripheral blood samples of patients affected by hematologic disorders involving the megakaryocytic line were examined at the electron microscope. While in idiopathic thrombocytopenic purpura the megakaryocytes appeared almost normal, in primary thrombocythemia there were various ultrastructural alterations interpreted as a counterpart of ineffective thrombocytopoiesis. In one patient with blastic chronic myeloid leukemia and in another with acute megakaryoblastic leukemia, the electron microscope study was very useful in the identification of immature megakaryocytes. In fact, analysis of various ultrastructural parameters allowed some blast cells to be attributed to the megakaryocytic series. Furthermore, platelet demarcation system abnormalities and alterations of the circulating thrombocytes confirm the hypothesis that there is a block in megakaryocytic maturation.

Blood Platelets↗

Idarubicin in blastic crisis of chronic myelogenous leukemia.

BACKGROUND: Blastic crisis (BC) is the terminal event in the natural history of most chronic myelogenous leukemia (CML) patients. Depletion of the normal stem cell compartment, as well as the proliferative advantage and frequent pharmacoresistance of the blastic clone, contribute to the poor prognosis of CML patients in this phase. Recent clinical trials have shown that idarubicin (IDR) in combination with cytosine arabinoside (ARA-C) is more active than daunorubicin at comparable doses in acute myelogenous leukemia (AML). Furthermore, IDR alone also exhibits antitumoral activity in the BC of CML. METHODS: Twelve Ph+ CML patients in BC (male 8, female 4; median age 45 yrs., range 19-55 yrs.) were treated with IDR 12 mg/m2/die for 3 consecutive days in sequential combination with Ara-C (1 hour i.v. infusion) 120 mg/m2/12 hrs. for 7 consecutive days. BC exhibited a myeloid phenotype in 9 and a lymphoid phenotype in 3 cases. Median duration of the previous chronic phase had been 36 months (range 6-180). RESULTS: Clearing of peripheral and bone marrow blasts was achieved in all but one patient. Three other patients were classified as resistant because of blastic regrowth, and 3 died of infection during postchemotherapeutic aplasia. Two patients achieved complete remission (CR) and 3 partial remission (PR). The median duration of response was 11 months (range 6-32). CONCLUSIONS: In BC of CML the IDR/Ara-C combination led to an encouraging rate of either partial or complete responses. The relatively long duration of unmaintained response was even more interesting, with the duration of PR approaching that of CR. These data suggest that IDR should be considered as one of the first-line drugs in the treatment of BC of CML.

Adult↗

Chronic myelogenous leukemia: state of the art.

Recent contributions from molecular biology, biotechnology and recombinant DNA applications have led to important clinical and therapeutic advances in chronic myelogenous leukemia (CML). Developments in the methodology of genetic investigation have clarified the molecular alterations brought about by the appearance of the Philadelphia chromosome. It is possible that the hybrid bcr/abl gene plays an important role in the pathogenesis of CML by subverting the mechanism of homeostasis through the uncoordinated activation of cell growth stimulating and regulating factors. Further improvements have been brought about by the polymerase chain reaction (PCR) which permits an indirect identification of the fusion gene and the study of minimal residual disease during remission after chemotherapy and bone marrow transplantation (BMT). Clinical trials have shown that alpha-interferon, alone or in association with chemotherapy, induces long term clinical and cytogenetic remission in those CML patients in whom BMT from either related or unrelated donors cannot be performed. Allogeneic BMT seems to be the treatment of choice in younger people. However, since a minority of subjects have HLA identical siblings, the possibility of using unrelated donors to provide long term disease free survival has been explored even if the availability of a compatible donor is the primary limiting factor. The development of in vivo and in vitro purging procedures has aroused new interest in autologous bone marrow transplantation. This procedure benefits particularly from biotherapeutic agents which selectively act on the marrow by suppressing bcr/abl positive cells.

Antineoplastic Agents↗

Ciprofloxacin for infection prophylaxis in granulocytopenic patients with acute leukemia.

Forty consecutive neutropenic patients with acute leukemia receiving oral ciprofloxacin (500 mg twice daily) and ketoconazole (200 mg daily) for selective intestinal decontamination were compared retrospectively with 33 comparable patients treated with polymyxin E (1,500,000 U x 3/day) and nystatin (1,000,000 U x 3/day). The incidence of febrile episodes was slightly lower in ciprofloxacin treated patients (87.5% vs 100%). No gram-negative sepsis was observed in this group compared with seven cases in patients receiving polymyxin E (p less than 0.01). Furthermore, eight patients in ciprofloxacin group (20%) had gram-positive sepsis, compared with five (15.5%) in the polymyxin E group. The incidence of documented fungal infections was similar in the two groups. Ciprofloxacin appears to be an effective agent for the prevention of gram-negative infections in granulocytopenic patients with acute leukemia, but may contribute to a shift in the type of infections in these patients towards those caused by gram-positive microorganisms, intrinsically fairly sensitive or with acquired drug resistance.

Agranulocytosis↗

[Cellular metabolism of sodium and hypertension].

Essential hypertension develops from interactions between genetic and environmental components. Studies on cell membrane ions (in particular the sodium ion) transport in essential hypertension were originally carried out in order to better understand the roles these two components play in a less complex system than the overall organ system or the single organs involved in blood pressure regulation. The theory supporting this experimental approach is based on the observation that cell membrane function affects all the phenomena involved in blood pressure regulation. Receptor function, hormonal secretion, cell volume regulation, ion transport and ion composition of the cell are all regulated at the cell membrane level. However the problem of the relevance of cellular sodium metabolism in the pathogenesis of essential hypertension and of the interpretation of the many conflicting results has grown in complexity with the growing mass of data published in the literature. At least part of this complexity seems related to methodological problems but part is surely due to real differences among the various populations or subpopulations studied. This review analyzes the main sources of the discrepancies, the different ion transport systems and the end point of the overall transport system as well as the steady state intracellular cation concentration in both genetic animal models of essential hypertension and in man.

Animals↗

Single-institution results of autologous bone marrow transplantation in acute myeloid leukemia.

BACKGROUND: Current results of autologous bone marrow transplantation (ABMT) suggest that this procedure may prolong disease-free survival (DFS) in patients with acute myeloid leukemia (AML). MATERIALS AND METHODS: Over the last ten years, 29 AML patients received unpurged autologous bone marrow (BM) after a conditioning regimen including Ara-C (3 g/m2/12h, days -9, -8), CTX (60 mg/kg/day, days -6, -5) and TBI (3.33 Gy/day, days -3 through -1). In 21 patients, ABMT was performed as late intensification after first CR. Eight more relapsing patients were autografted after the achievement of second CR. RESULTS: Three patients died from transplant-related complications. In the remaining patients, mean times to WBC and platelet recovery were, respectively, 23 days (range 13-55) and 55 days (range 22-790). Follow-up for censored patients ranged from 1 to 120 months. Relapse occurred in 7 patients (5 in first and 2 in second CR). Overall 5-year DFS and event-free survival (EFS) chances were, respectively, 67.3% and 60%, with no statistically significant differences between first (DFS = 67.3%, EFS = 60.3%) and second CR (DFS = 68.6%, EFS = 60%). DISCUSSION: Apart from obvious selection biases, our study suggests that outcome in first CR AML patients is improved by ABMT. Long-term DFS and EFS are clearly better than when conventional post-remission chemotherapies are used. The greater antileukemic potential of ABMT is further underlined by the results in patients autografted in second CR, when conventional chemotherapy is almost never curative.

Acute Disease↗

Efficacy of different prophylactic antifungal regimens in bone marrow transplantation.

BACKGROUND: Fungal infections still represent a major clinical problem in neutropenic patients; the recent availability of active imidazole derivatives, particularly fluconazole and itraconazole, has increased interest in prophylaxis. MATERIALS AND METHODS: Fifty-nine consecutive bone marrow transplant (BMT) recipients were randomized to receive either itraconazole 400 mg/day or fluconazole 300 mg/day as oral antimycotic prophylaxis during the pancytopenic phase; they were retrospectively compared with a historical control group of 30 patients who had received fluconazole 50 mg/day. Every febrile episode was treated with the same empirical antibiotic combination; amphotericin-B was added after 4-5 days in the case of persistent fever. Proven or suspected mycotic infections and the empirical use of amphotericin-B were considered as failures of prophylaxis. RESULTS: There were no differences in the number of febrile episodes in the three groups. Five patient died of bacterial sepsis: two in the fluconazole 300, two in the itraconazole and one in the fluconazole 50 group. The addition of amphotericin-B was required in 12, 16 and 11 cases, respectively, in the three groups. There were four documented fungal infections in the intraconazole and one in both fluconazole groups; three suspected fungal infections were observed in the fluconazole 300 group and two in both the itraconazole and the fluconazole 50 group. None of the differences were statistically significant. CONCLUSIONS: The present results indicate that high-dose fluconazole and itraconazole are equivalent; neither of them was superior to low-dose fluconazole, which is regarded as being devoid of prophylactic activity against systemic mycoses.

Adolescent↗