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Biomedical subjects

E E Polli

Publications and source records attributed to E E Polli.

At least 37 records · Page 2Linked to original sources

Cyclosporin A in the treatment of severe aplastic anemia: description of a case complicated by the development of tubercular pericarditis during treatment.

We report on a 62 year-old woman who developed a severe aplastic anemia requiring frequent packed red cell and platelet transfusions. Since conventional pharmacological therapy was ineffective, treatment with Cyclosporin A was started, resulting in a significant increase of leukocyte, platelet, and red cell counts. However, 5 months after the beginning of Cyclosporin A treatment, despite a past medical history not significant for clinical tuberculosis, the patient developed tubercular pericarditis. This report underlines the need for a careful follow-up of Cyclosporin A-treated patients aimed at a prompt diagnosis of possible infectious complications.

Anemia, Aplastic↗

Chronic myelogenous leukemia following radiation therapy for testicular seminoma.

A 43-year-old man was treated with orchiectomy and radiotherapy for testicular seminoma. Four years later, he developed a typical Philadelphia chromosome positive chronic granulocytic leukemia. Since the patient was not eligible for bone marrow transplantation, he was treated with busulfan. Long term follow-up of patients who received radiotherapy for testicular seminoma is warranted in order to detect possible secondary tumors.

Adult↗

[Pulmonary mycosis as a complication of acute leukemia in the adult. Diagnostic study].

Pulmonary fungal infections complicating hematological malignancies are difficult to diagnose antemortem because clinical findings are actually considered to be not specific. From December 1984 to June 1986 we documented the clinical findings in sixteen patients, 9 with ANLL, 6 with ALL and 1 with CML + BC; all patients were diagnosed as pulmonary fungal infection and treated for this complication. Pulmonary infiltrates occurred after severe aplasia (range 5-90 days) or during bone marrow relapse. We studied pulmonary signs and symptoms (pleuritic pain, cough, hemoptysis, shortness of breath, rales, rub, bronchial murmur) both at the beginning and during the management of this infectious complication and we related them to chest x-ray findings, the duration of granulocytopenia, and fever. Our purpose was to identify clinical characteristics for these episodes and establish roentgenological criteria for prognosis. These findings should improve the possibilities for an early diagnosis and prompt treatment.

Acute Disease↗

Acute gangrene of the scrotum and penis in four hematologic patients. The usefulness of hyperbaric oxygen therapy in one case.

We describe four cases of Fournier's gangrene complicating the postchemotherapy aplastic phase (polymorphonuclear cells [PMN] less than 500/microliter) in three patients with acute leukemia and one patient with non-Hodgkin's lymphoma. Blood and local cultures from two patients contained Pseudomonas aeruginosa, and local cultures from another patient grew both P. aeruginosa and Proteus rettgeri. Early recognition and aggressive antibiotic and surgical treatment with granulocyte recovery were fundamental factors in resolution of the gangrene in three of the four patients. Hyperbaric oxygen therapy, never reported in hematologic patients, was also very useful in one patient in whom the clinical course was particularly acute.

Adolescent↗

Immunohistochemical evaluation of bone marrow involvement in hairy cell leukemia during interferon therapy.

Bone marrow biopsies from 7 patients afflicted with hairy cell leukemia were studied with a panel of monoclonal antibodies at different intervals during alpha recombinant interferon therapy. Monoclonal antibodies Dako-LC and F 8.11.13 were used because they are highly reactive with hairy cells, and 82H3 and LeuM 1 were also utilized to identify respectively the residual hemopoietic and myeloid tissue. All antibodies are reactive on sections of formalin-fixed, paraffin-embedded biopsy material. Before therapy a uniform hairy cell infiltrate was present and very little tissue was visible even after immunohistochemical staining. During therapy, identification of hairy cells in routine biopsies was difficult, since they were mixed with normal cells and the bone marrow was generally hypoplastic. Immunohistochemical stains seem to allow better identification of hairy cells and a more precise estimate of the degree of repopulation by normal bone marrow cells. It was evident, especially after immunocytochemical analysis, that interferon drastically reduced the extent of the infiltrate and allowed recovery of normal hemopoiesis, but did not produce complete remissions.

Antibodies, Monoclonal↗

Idarubicin in sequential combination with cytosine arabinoside in the treatment of relapsed and refractory patients with acute non-lymphoblastic leukemia.

Sixteen adult patients with refractory acute non-lymphoblastic leukemia (ANLL) underwent reinduction therapy with idarubicin (12 mg/m2) i.v. on days 1-3) followed by cytosine arabinoside (120 mg/m2 every 12 h on days 4-10). Patients achieving complete remission (CR) received consolidation and early intensification courses which included idarubicin at lower dosage. CR was reached after a single course in 70% of the patients treated at first relapse, and two of the five subjects previously resistant to daunorubicin-containing regimens responded to the idarubicin protocol. The median duration of CR was 11 months. Gastrointestinal side-effects were not important; mild and reversible ECG changes were noted whereas delayed cardiac toxicity was not observed despite previous treatment with daunorubicin. These encouraging results confirm the efficacy of idarubicin in treating acute leukemia and suggest it may have a major role in the treatment of relapsed and refractory patients with ANLL.

Acute Disease↗

Inhibitory activity of a synthetic pentapeptide on leukaemic myelopoiesis both in vitro and in vivo in rats.

The synthetic pentapeptide pGlu-Glu-Asp-Cys-Lys has recently been proposed as the active component of a granulocyte-derived inhibitor of normal haematopoiesis. We investigated its biological activity on leukaemic myelopoiesis both in vitro and in vivo in rats. Three different human permanent myeloid leukaemic cell lines (HL60, KG1, ML3) and a rat transplantable acute myeloid leukaemia (Shay leukaemia) were studied. Neither HL60 nor KG1 were sensitive to the peptide whereas a consistently reproducible inhibition of 3H-TdR uptake was observed in ML3 cells. This effect was not due to a unspecific toxic action on target cells and was spontaneously reversible. When injected i.p. twice daily at an appropriate concentration in rats bearing Shay leukaemia, the peptide caused a significant increase in survival. Our results therefore indicate that the synthetic pentapeptide studied inhibits not only normal but also leukaemic myelopoiesis.

Animals↗

Bone marrow histological modifications induced by alpha interferon in hairy cell leukemia.

This paper reports the bone marrow histological picture in 7 patients with hairy cell leukemia treated with recombinant interferon. Bone marrow biopsies were performed at diagnosis, after 1, 3 and 7 months from the beginning of treatment and at 12 months at treatment suspension. The main modifications observed were a conspicuous reduction of hairy cell infiltrate, profound hypoplasia induced by the drug, early evidence of focal erythropoiesis followed by the appearance of other hematopoietic series and a progressive reduction of the reticulum. The clinical response to interferon therapy was good in all the patients studied; however future studies will have to evaluate the duration of response after treatment suspension.

Biopsy↗

Plasma cyclic nucleotide levels in acute leukemia patients.

To verify the clinical usefulness of extracellular cyclic nucleotide determination as a tumor marker, plasma cyclic AMP (cAMP) and cyclic GMP (cGMP) levels were measured in 70 normal subjects and 173 acute leukemia patients studied in different stages of their disease. Mean plasma cAMP levels were similar in leukemic and normal subjects, although in 48 patients in the active stage of the disease, first diagnosis, or relapse, the cAMP values were below the normal range, and most of these patients failed to respond to chemotherapy. Plasma cGMP levels were markedly elevated in untreated patients, normalized in all patients who attained complete remission, and increased promptly to pretreatment values in patients who relapsed, suggesting that their determination may be useful to monitor the patients' response to treatment.

Acute Disease↗

Oral idarubicin in adult acute leukemia: a preliminary experience.

Twelve patients affected by different types of acute leukemia received idarubicin (4-demethoxy-daunorubicin) by oral route at the total dosage of 45, 60 or 90 mg/m2 distributed over three consecutive days. Drug response was assessed by the decrease in blast cells in peripheral blood and showed some variations between the different types of leukemia. Acute myelogenous leukemia patients and those with blastic crisis of chronic myeloid leukemia appeared to be the more responsive groups; however, the lower dose schedule could explain the less satisfactory results obtained in lymphatic leukemia patients. Data suggest that idarubicin is absorbed rapidly after oral ingestion, in spite of nausea and vomiting, which appeared 3-4 h later and were easily controlled by antiemetic therapy. The purpose of fractionating the drug dosage over three consecutive days is to prolong in the blood an elevated concentration of the main idarubicin metabolite (13-dihydro-derivative), which presents in experimental models an antileukemic potency similar to the parent compound. This study confirms that idarubicin is effective in acute leukemia also by oral route. This formulation could offer some advantages for subjects who cannot tolerate parenteral chemotherapy and it could be proposed in maintenance leukemia protocols.

Acute Disease↗

Inhibition of proliferation of human leukaemic cell populations by deferoxamine.

Deferoxamine is a hydroxylamine which binds ferric ions to form a highly stable complex. Since iron is thought to be required at a critical stage for cell proliferation, we investigated the effect of deferoxamine on the proliferative activity of human leukaemic cell populations in vitro by means of 3 permanent cell lines, HL60, U937 and 8402. We found deferoxamine to be a potent inhibitor of DNA synthesis and proliferation of leukaemic cells, acting by accumulating treated cells at the early S phase of the cell cycle. Suppression of leukaemic proliferation was obtained at deferoxamine concentrations in the range usually achieved in the treatment of patients for iron overload. Deferoxamine might therefore warrant further investigation as a potentially useful agent for leukaemia chemotherapy.

Cell Division↗

Human recombinant interferon alpha-2C enhances the expression of class II HLA antigens on hairy cells.

Isolated splenic hairy cells from three untreated patients were cultured in presence of recombinant human interferon alpha-2C (IFN alpha). Ultrastructural cytochemistry and immunophenotype analysis with a large panel of monoclonal antibodies were performed to study cellular modification induced by IFN alpha. Hairy cells showed a typical pheno-type: Smlg+, B1+, BA1+/-, anti-Tac+, OKDR+, Leu-M5+, HC2+, TRAP+, myeloperoxidase-. Under our experimental conditions, we found no direct cytotoxic effects or significant variations in morphology, cytochemistry, and percentage of reactivity with the tested monoclonal antibodies. After culturing in the presence of different doses of IFN alpha, we observed a significant enhancement of the expression of class II HLA antigens as demonstrated by increased fluorescence for OKDR, OKla, Leu-10 at fluorescence-activated cell sorting analysis. In agreement with this finding IFN alpha-treated hairy cells showed an increased stimulatory capacity v allogeneic T cells in one-way mixed lymphocyte reaction. To our knowledge this is the first report describing the induction of class II HLA antigens on hairy cells by IFN alpha.

Antibodies, Monoclonal↗

Functional and multimarker analysis of T-cell chronic lymphocytic leukaemia.

The morphology, immunophenotype, cytoenzymatic and functional activities of T lymphocytes from 4 patients with chronic lymphoproliferative disease of T-cell origin were studied. Clonal proliferation was demonstrated by distinctive chromosomal abnormalities involving chromosomes 2 and 14. Patients 1 and 2 were classifiable as OKT4+ T-cell chronic lymphocytic leukaemia (T-CLL) and patient 3 as OKT4+/OKT8+ T-CLL, with helper function in vitro only in patient 1. Patient 4 has low-grade lymphocytosis with benign clinical course, with cells showing morphology of large granular lymphocytes (LGL), and immunophenotype HNK-1+, ER+, Fc gamma receptor+, OKT3+, OKT11+ and OKT8+, as well as natural killer activity, radiosensitive suppressor activity on Ig secretion and responsiveness to PHA; this case was interpreted as LGL leukaemia. This study indicates that a large proportion of cases of true T-CLL may belong to the OKT4 subset, and that extensive investigations should be made of the lymphocytic OKT8+/T gamma forms to characterize them precisely.

Aged↗

Plasma cyclic nucleotide levels in patients with homozygous beta-thalassaemia.

To investigate the possibility that a proliferative non-neoplastic process influences extracellular cyclic nucleotide concentrations, we measured plasma cyclic AMP and cyclic GMP levels in 38 patients with homozygous beta-thalassaemia. This group consisted of 20 patients with thalassaemia major transfused regularly (mean pre transfusion Hb levels, 11 g/dl), and 18 patients with thalassaemia intermedia who did not require regular blood transfusion (mean Hb levels, 8.7 g/dl). In the patient group, plasma cyclic AMP levels were similar to those of 37 normal subjects matched for age and sex, whereas plasma cyclic GMP levels were markedly higher. Moreover, in the thalassaemic patients there was a significant negative correlation between plasma cyclic GMP levels and haemoglobin concentrations, suggesting that their marked erythroid hyperplasia may play a role in determining alterations in extracellular cyclic GMP levels.

Adolescent↗