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Biomedical subjects

A Cortelezzi

Publications and source records attributed to A Cortelezzi.

At least 55 records · Page 3Linked to original sources

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↗

Recombinant interferon alfa-2C versus polychemotherapy (VMCP) for treatment of multiple myeloma: a prospective randomized trial.

Forty-two previously untreated patients with multiple myeloma were entered in a prospective, randomised trial comparing recombinant interferon alfa-2C monotherapy with VMCP (vincristin, melphalan, cyclophosphamide and prednisolone). Both treatment arms were comparable for the stratification variables such as paraprotein type, stage of disease, and renal function. Rec. interferon effected 14% responses and 29% minor responses, while 57 and 32% of VMCP-treated patients achieved a pathologically documented remission (P less than 0.001). The time on initial treatment was significantly shorter in the IFN group (3.2 months) than in the VMCP group (7.6 months). In four patients in the IFN arm, primary treatment had to be changed according to progressive or severe stationary disease. Since all four patients responded to second line therapy (VMCP) no significant difference has been observed between the two groups in survival (median follow-up greater than 12 months). Despite this clear superiority of the conventional four-drug polychemotherapy, there was some suggestion that IFN might be particularly active in cases with low tumor-burden (stage I, II), and light-chain or IgA paraprotein type.

Adult↗

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↗

Treatment with recombinant interferon-alpha-2C: multiple myeloma and thrombocythaemia in myeloproliferative diseases.

Forty-two patients with multiple myeloma were allocated to two groups to receive either polychemotherapy with vincristine, melphalan, cyclophosphamide and prednisolone, or recombinant interferon-alpha 2C monotherapy. The response rate of 43% in the interferon group was significantly lower than that in the chemotherapy group (89%). Patients with stage I disease showed better response rates than those with stage II or stage III disease. Eleven patients with thrombocythaemia due to polycythaemia vera, chronic myeloid leukaemia or essential thrombocythaemia were treated with recombinant interferon-alpha 2C and complete remissions were achieved in 7 of the 8 evaluable patients. Side-effects were common on interferon therapy, but could be reduced by dose reduction and were reversed by cessation of treatment.

Adult↗

Plasma cyclic nucleotide levels in monitoring acute leukemia patients.

To verify the clinical usefulness of plasma cyclic nucleotide determination as a tumor marker, levels were measured in 52 normal subjects and in 106 acute leukemia patients. In untreated patients plasma cyclic GMP (cGMP) levels were markedly elevated, whereas cyclic AMP levels did not significantly differ from those of normal subjects. Plasma cGMP levels normalized in all patients who attained complete remission and remained in the normal range during all the remission period. In the patients who relapsed, an early increase in cGMP levels to the pretreatment values was observed, thus suggesting that their determination may be of clinical relevance in monitoring the patients' response to treatment.

Acute Disease↗

[Interferon in the treatment of multiple myeloma].

The effect of recombinant interferon-alpha-2C monotherapy was compared with the efficacy of VMCP-polychemotherapy in 42 patients with multiple myeloma in a prospective randomized multicenter trial. IFN-treatment induced remissions (R) in 2 (14%) and partial remissions (PR) in 4 (29%) out of 14 evaluable patients. 7 patients remained stable. Polychemotherapy induced R in 11 (57%) and PR in 6 (32%) of 19 evaluable patients. 2 (11%) patients remained stable. IFN was preferentially active in patients with low tumor burden and patients with IgA paraprotein. The proportion of responders (R + PR) was significantly lower in the IFN-arm (43%) compared to the polychemotherapy group (89%; p less than 0,001).

Antineoplastic Combined Chemotherapy Protocols↗

Prognostic significance of immunoglobulin phenotype in B cell chronic lymphocytic leukemia.

Seventy-six consecutive untreated patients with B cell chronic lymphocytic leukemia (B-CLL) and classified according to Binet's staging system were studied at the clinical presentation. Several immunologic parameters (number of total and T circulating lymphocytes and their surface membrane immunoglobulin [Smlg] phenotypes and levels of serum Ig) were evaluated with the aim of identifying a biologic marker of prognostic relevance. In this series of persons, Binet staging confirmed its usefulness as a prognostic index (P less than .001). With regard to Smlg, they were mu-type in 41 cases (53.9%), mu-type plus delta-type in 29 cases (38.2%), alpha-type in one case, and not detectable in five cases. No correlations were found between clinical stage and immunoglobulin phenotype, although all but one patient in stage C showed mu-type Smlg alone. On analyzing the survival curves of our patients according to different Smlg phenotypes, we found that patients with only mu-type Smlg had a poorer prognosis (P less than .05) than those with mu-type plus delta-type; this difference was even more significant (P less than .01) in patients in stage A, whereas there were no statistical differences in those in stages B and C. Because the appearance of surface heavy chain of delta-type could be an expression of cell maturation, these results suggest that in B-CLL the presence of phenotypically more mature leukemic cells may correlate with better clinical prognosis, particularly in the early phase of the disease.

Actuarial Analysis↗

Value of CT scanning in the diagnosis of CNS mycotic involvement: report of 3 cases.

Fungal infections of the CNS are becoming an increasingly serious problem in immunosuppressed patients. We describe three patients with malignant blood disease who in the course of systemic fungal infection presented cerebral involvement. The nature, site and extent of the cerebral involvement were defined by computed tomography (CT). Further, in one patient it was possible to follow the course of the lesion and assess the effectiveness of antimycotic therapy by CT because of its noninvasiveness and repeatability.

Adult↗

[Pathogenic flora in hematology patients. Gram-negative germs and their in vitro sensitivity to antibiotics].

The results of microbiological research carried out on haematological patients admitted to the same ward are reported. The pathogenic flora observed consisted mainly of gram-negative germs (60%). Pseudomonas infections represented the most important problem because of their frequency and the consequent clinical problems. The in vitro sensitivity of 306 strains of gram-negative germs to 11 different antibiotics has been analysed. Amikacin proved to be easily the most effective antibiotic against isolated pathogens.

Amikacin↗

Presence of circulating immune complexes in patients with chronic lymphocytic leukaemia. Correlations between clinical and immunological features.

The presence of circulating immune complexes (CIC) was evaluated in 60 untreated patients with chronic lymphocytic leukaemia with the polyethylene-glycol precipitation assay. The mean values of optical density (OD) in patients' sera was 0.161 +/- 0.121 compared with control values of 0.082 +/- 0.045 (P less than 0.001). Sera of 16 patients gave OD values higher than 0.172 (mean of controls plus 2 SD) and were considered positive for the presence of CIC. Using the new staging proposed by Binet for CLL we did not find any correlation between presence of CIC and stage of the disease. On the contrary, it was possible to correlate the presence of CIC with the stability of the disease: CIC were found in only 2 of the 22 patients (9.1%) with progressive disease but in 10 of the 30 patients (33.3%) with stable disease (P less than 0.05). CIC were present in 12 of the 38 patients in whom the only surface immunoglobulins present were IgM, but in only 1 of the 14 patients in whom both IgM and IgD were contemporaneously present on the lymphocyte surface. No correlations were found between levels of serum immunoglobulins and presence of CIC.

Adult↗

Empiric treatment of infections in granulocytopenic patients with acute leukemia: a study on amikacin-carbenicillin-cotrimoxazole.

The amikacin-carbenicillin-cotrimoxazole combination was used as an empiric treatment for febrile episodes in patients with acute leukemia and severe granulocytopenia. The choice of drugs was based on the finding in our institute that the majority of infections are caused by gram-negative rods, particularly Pseudomonas, with high percentage of strains resistant to gentamycin and tobramycin. Granulocyte transfusions were given to the patients who did not show satisfactory clinical improvement 48 h after start of antibiotic therapy. There were cures in 84.6% of the febrile episodes treated with this antibiotic combination, including five of eight episodes of microbiologically confirmed bacteremia. Survival after 21 days of antibiotic therapy amounted to 89.1%. Renal toxicity occurred in 10.9% of the episodes treated. The prompt use of this antibiotic combination seems to be a safe and efficacious therapeutic tool for treating these high-risk patients.

Acute Disease↗

Osteolysis in chronic myeloid leukemia.

Four patients affected by chronic myeloid leukemia who developed osteolytic lesions in the course of the disease are described. According to the literature, the appearance of these alterations seems to signify an unfavorable prognosis, since they occur slightly before or even at the same time as the blastic transformation of the disease. However, in one case bone biopsy showed a metastasis of a solid tumor, emphasizing the importance of this procedure in order to give a more precise clinical evaluation, both diagnostic and therapeutic.

Biopsy↗

In vitro production of lymphocyte and granulocyte proliferation inhibitors (chalones?) from living cells.

Media conditioned with viable rat and calf spleen lymphocytes were seen to be able to inhibit 3H-thymidine uptake by rat thymocytes and the mitogenic response of human lymphocytes to PHA but not bone marrow cells proliferation. The inhibitor appeared to have a molecular weight greater than 50,000 daltons, as determined by Amicon Diaflo ultrafiltration. Media conditioned with rat granulocytes had a similar tissue specific but species non-specific inhibitory action. Also human leukemic cells appeared able to produce in vitro an inhibitor of cell proliferation when a certain degree of differentiation was present.

Animals↗

Diagnosis and treatment of fungal infections in patients with hematologic malignancies.

A diagnosis of deep-seated mycosis was made in 54 patients with hematologic malignancies, severe neutropenia and fever, based on a set of clinical and laboratory criteria. Standardized antifungal treatment was started in 31 patients who seven days after onset of fever had not responded to antibiotics; the fungal infection was cured in 13, all of whom had a simultaneous remission of neutropenia, whereas the other 18 who did not respond to antifungal treatment, all had a falling or static neutrophil count. None of the 23 patients who were given no or inadequate antifungal treatment survived regardless of the neutrophil count and/or phase of the hematologic disease. We discuss the suitability of utilizing empirical criteria for a diagnosis of disseminated fungal infection as a basis for starting antifungal therapy in this type of patient.

Adolescent↗

[Endothelial progenitor cells in systemic sclerosis: their possible role in angiogenesis].

BACKGROUND: Recently, several studies have demonstrated the presence of circulating endothelial progenitors (CEPs) responsible for angiogenesis. Notably, these cells are able to migrate to ischemic tissues and differentiate in situ in mature endothelial cells. Aim of this study was to assess the presence of CEPs in the peripheral blood of patients with Sistemic Sclerosis (SSc) and evaluate their significance as an attempt of re-vascularization MATERIAL AND METHODS: Samples of peripheral blood from 40 healthy subjects and 56 patients with SSc were studied. Five-parameter, 3-color flow cytometry was performed with a FACScan. CEPs were defined as CD45 negative, CD34 and CD133 positive. In addition, plasma levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were detected by commercial ELISA (R&D Systems). RESULTS: Levels of CEPs (CD133+/CD34+/CD45-) were significantly higher in patients with SSc in comparison to HC (P = 0.01). No correlation was found between CEPs and any clinical parameter of disease neither activity score. CEPs were significantly higher in the group of patients with early disease, while their number decreased in the late phases of disease. Plasma levels of VEGF, but not bFGF, were significantly higher in SSc in comparison to HC (P<0.001) but no correlation was found between VEGF concentrations and CEP number. CONCLUSIONS: The presence of CEPs in patients with SSc suggest that sclerodermic hypoxic tissues could induce the mobilization of bone-marrow derived cells in an attempt to provided new vessels, in the early phase of the disease, at least.

Adult↗