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Biomedical subjects

L Ferrari

Publications and source records attributed to L Ferrari.

At least 109 records · Page 6Linked to original sources
PubMed1993

Reduced expression of macrophage-associated antigens on alveolar mononuclear phagocytes from acquired immunodeficiency syndrome.

In this study we evaluated the phenotype of alveolar mononuclear phagocytes recovered from the bronchoalveolar lavage fluid of 24 patients with human immunodeficiency virus infection (AIDS-related complex 8 patients. AIDS 16 patients) and 8 healthy individuals by using a panel of monoclonal antibodies known to react with tissue macrophages, in combination with a flow cytometer. The results showed that 90% of patients with AIDS present a marked reduction in the expression of several antigenic determinants (in decreasing order: CD68, CD36, CR1, CD11c, HLA-DR). The levels of antigen expression by flow cytometry seem to decline with disease progression, showing the most dramatic perturbations in patients with full-blown AIDS associated with pulmonary infections (especially Pneumocystis carinii pneumonia) and lower peripheral CD4 lymphocyte counts. In contrast, patients with AIDS-related complex or AIDS without histological or cultural evidence of pulmonary involvement showed, respectively, only minimal or medium antigenic decreases. However, only a minor proportion (16%, 20%, 20%, 25%, and 25% respectively) of human immunodeficiency virus infected patients (mostly with AIDS) had a significant reduction of the levels of CD4, CD14, CD45R, CD11b, and CD16 antigens in the alveolar macrophages. Since macrophages play a central role in the pathogenesis of AIDS, it may be postulated that the loss of various phenotypic markers on alveolar mononuclear phagocytes (some of them known for their important immunoregulatory actions) could have an important part in the pathogenesis of human immunodeficiency virus induced immunosuppression, and thereby condition the abnormal susceptibility to pulmonary diseases typical of human immunodeficiency virus-infected patients.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Chromosome aberrations in CD34-positive acute myeloid leukemia. Correlation with clinicopathologic features.

Morphologic, immunologic, and cytogenetic features were studied in 30 newly diagnosed patients with CD34-positive (CD34+) de novo acute myeloid leukemia (AML) in comparison with 30 patients with CD34-negative (CD34-) AML. Karyotype at diagnosis was abnormal in 25/30 CD34+ AML patients, of which nine had major karyotype aberrations (MAKA). Clonal chromosome changes were detected in 9/30 patients with CD34- AML. The most frequent chromosome aberration in CD34+ patients was -5/5q-, an aberration showing a strong association with the M2 FAB subtype of AML. Other recurring chromosome changes involved chromosome 16q (four cases) and chromosome 17p (three cases). Total or partial monosomy 7q was detected in three cases. Among CD34- AML, two patients had the classical t(15;17) and two had structural aberrations of 6q. Among patients with CD34+ AML, nine had MAKA in association with trilineage myelodysplasia (TMDS). TMDS was infrequent in CD34+ AML without MAKA and in CD34- AML. Complete remission (CR) was achieved in 8/30 CD34+ AML (26%), as compared with 22/30 CD34- AML (73%), and median survival was 2 months in the former group and 8 months in the latter. No patient with CD34+ AML and MAKA achieved CR, whereas 8/21 CD34+ AML without complex chromosome changes or with normal karyotype achieved CR. In conclusion, a distinct cytogenetic profile may be associated with CD34+ AML. Cytogenetic findings in CD34+ AML may be clinically relevant in that they may disclose a subset of patients with MAKA with a low CR rate.

Adult↗
PubMed1993

Carboplatin in combination as first-line therapy in advanced breast cancer.

Carboplatin, a platinum analog with single-agent activity in previously untreated breast cancer, is characterized by comparatively less renal toxicity and emesis than cisplatin. We combined carboplatin at different dose levels [from 200 to 350 mg/m2 by intravenous (IV) infusion on day 1] with 5-fluorouracil (500 mg/m2 IV on days 1 and 8) and cyclophosphamide (500 mg/m2 IV on day 1), with all three drugs recycled every 28 days, to evaluate anti-tumor activity and toxicity of this novel combination [5-fluorouracil/carboplatin/cyclophosphamide (FCC)] in untreated locally advanced (LABC) or metastatic breast cancer (M+). Of 37 patients treated between March 1990 and August 1991 [LABC 25, M+ 8; World Health Organization (WHO) performance status, 0-1; median number of treatment cycles, 5; median follow-up, 20 months], 33 are evaluable for response and toxicity. The overall complete plus partial remission rate was 57% (LABC 68%, M+ 25%). The median duration of response was 19+ months. The cumulative carboplatin dose ranged from 800 to 2350 mg/m2 (median, 1450 mg/m2). In this series, no correlation was observed between the carboplatin dose level and response rate or toxicity. Leukopenia and thrombocytopenia represented the most frequent toxicities. WHO grades 3 and 4 neutropenia were documented in 34% and 8% of patients, respectively. Thrombocytopenia below 50 x 10(9)/l was observed in 8%. No renal toxicity was observed, and moderate emesis occurred in 67% of patients. These results indicate that FCC is an active and relatively safe combination for the treatment of advanced breast cancer in patients not previously treated with chemotherapy.

Adult↗
PubMed1993

Interleukin-1 beta differentially represses drug-metabolizing enzymes in arthritic female rats.

Experimental arthritis and inflammation have been reported to reduce liver cytochrome P-450-dependent mono-oxygenase activities with subsequent impairment of drug metabolism. Interleukin-1 beta (IL-1) is among the proven mediators of both inflammation and P-450 decrease, although some paradoxical effects were sometimes reported in experimental models of arthritis. The aim of the present study was to evaluate the main liver drug-metabolizing isoenzymes during established collagen-induced arthritis in rats, and to investigate whether a systemic IL-1 treatment was able to mimic or sometimes to reverse the influence of the inflammatory process on these enzymes. Arthritis was induced on day 0 by type II collagen and a low dose (0.2 mg) of N-acetylmuramyl-L-alanyl-D-isoglutamine, and human recombinant IL-1 was administered s.c. at the daily dose of 0.02, 0.2 or 2.0 micrograms per arthritic rat, from day 21 to 25 and on day 28. Ethoxyresorufin-O-deethylation was depressed 6-fold in arthritic rat liver microsomes and the highest dosage of IL-1 potentiated this depression. Pentoxyresorufin-O-deethylation decreased by 50% in arthritic rat, a dose-dependent decrease being observed after IL-1 treatment. Progesterone 6 beta-hydroxylation and P-450 IIIA protein increased by 2-fold in both untreated arthritic rat liver microsomes and those treated by the lowest dose of IL-1. The two higher doses decreased this activity, vs. the dose, to reach the naive level. Lauric acid hydroxylation increased 2-fold in arthritic rat and was further potentiated by IL-1. UDP glucuronosyl transferase IA2 activity was increased 2-fold in arthritic rats, with subsequent decrease after 2.0 micrograms of IL-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1992

Effects of interleukin-6 on cytochrome P450-dependent mixed-function oxidases in the rat.

Intravenous treatment of male rats with recombinant human interleukin-6 (rhIL6) at 50, 100 and 200 micrograms/kg (corresponding to 4, 8 and 16 x 10(4) U/animal, respectively) reduced the activities of hepatic microsomal cytochrome P450-dependent monoxygenases to varying degrees. Ethylmorphine-N-demethylase activity fell to 53% of control values, an effect similar to that induced by 2.5 mg/kg Escherichia coli lipopolysaccharide (LPS). Ethoxycoumarin-O-deethylase activity was also sensitive to inhibition, whereas IL6 had little effect on the activities of other P450-dependent enzymes, including ethoxyresorufin-O-deethylase. Pentoxyresorufin dealkylase activity, which is representative of the cytochrome P450 IIB 1/2 subfamily, was unaffected by IL6 whereas LPS reduced it to 33.7% of control values. Another hepatocyte-related parameter, serum concentration of alpha 1-acid glycoprotein (AGP), was increased by up to 3.5-fold over baseline by IL6 and 10-fold by LPS. Recombinant human interleukin-1 beta (rhIL1 beta) (10 micrograms/kg, corresponding to 5 x 10(4) U/rat) and recombinant human tumor necrosis factor alpha (rhTNF) (150 micrograms/kg corresponding to 24 x 10(4) U/rat) were both as potent as LPS (2.5 mg/kg) in increasing serum AGP levels and reducing hepatic microsomal monoxygenase activities. IL6 did not potentiate the effects of rhIL1 beta. Hepatic microsomal glucuronyltransferase activities were little affected by LPS and unaffected by rhIL6. Finally, rhIL6 was more potent after i.p. injection than after i.v. or s.c. injection. These results suggest that the effects of LPS, TNF and IL1 on the mixed-function oxidase system in vivo may be due partly to an induction of IL6 in vivo. The different sensitivities of the enzymes to IL6 but not to IL1 or TNF may be due to the involvement of two distinct mechanisms.

Animals↗
PubMed1992

Cationic content in multiple mammary cysts.

One hundred and ninety-six breast cyst fluid samples from 78 consecutive patients with multiple cysts were subdivided according to the K+/Na+ ratio: type 1 (K+/Na+ ratio > 1) and type 2 (K+/Na+ ratio < or = 1). Cysts of the same type were found in 57.7% of patients (concordant group). Such a finding suggests that in patients bearing multiple cysts, all aspirated fluids need to be classified on the basis of their cationic composition. In the concordant group, type 1 cysts were more frequent than in the discordant group (80.3% vs 59.5%, P = 0.002). High K+/Na+ ratios (> 4.0) were present in 64% of type 1 cysts in the concordant group compared to 37.7% in the discordant group (P = 0.001), which suggests a different activity of the epithelium lining the cyst wall.

Adult↗
PubMed1992

Non-radioactive in situ hybridization for the detection and monitoring of trisomy 12 in B-cell chronic lymphocytic leukaemia.

Non-radioactive in situ hybridization (NISH) with a chromosome 12-specific alpha satellite probe was performed on 20 patients with chronic lymphocytic leukaemia (CLL) with normal karyotype (15 cases) or with inadequate mitotic yield (5 cases) from mitogen-stimulated cultures. All patients had over 70% lymphocytes coexpressing the CD5/CD23 antigens. While less than 1% interphase nuclei showed three fluorescent spots in 16/20 patients, evidence of trisomy 12 in 15-25% interphase cells was detected in four patients. According to the FAB classification the diagnosis in these patients was typical B-CLL, stage III (Rai's staging system) in one case, CLL/PLL, stage II and III in two cases, PLL, stage III in one case. In order to confirm these results, NISH was repeated after 1 month in one patient and after 2 years in three patients. All patients had been treated with chemotherapy in the period between the two NISH experiments. In all cases a 1.8-3-fold increase of percentage of trisomic interphase cells was detected. These findings suggest that in B-CLL clones with trisomy 12 may have proliferative advantage over clonal B-lymphocyte without +12 and, possibly, that they may be more resistant to chemotherapy. We conclude that NISH is a sensitive technique allowing for the detection and monitoring of trisomy 12 in a fraction of B-CLL patients with normal karyotype or with no analysable mitoses despite employment of polyclonal B-cell mitogens.

Aged↗
PubMed1991

Changes in cell kinetics induced by primary chemotherapy in breast cancer.

Changes in the 3H-thymidine labelling index (3H-TdR LI) of primary tumor induced by cytoreductive chemotherapy were evaluated in 26 patients with locally advanced breast cancer subjected to mastectomy after different systemic therapies. A significant reduction of 3H-TdR LI by primary chemotherapy was observed in 11 cases. Changes in cell kinetics were related to the pretreatment proliferative activity: significant increases were observed in 70% of tumors with a very low 3H-TdR LI (less than 25%) and significant decreases in 100% of tumors with a very high 3H-TdR LI (greater than 7.0%). There was no correlation between pretreatment 3H-TdR LI and the objective clinical response, which was conversely related to posttreatment cell kinetics. The 2-year progression rate was lower for patients whose residual tumors after treatment had remained (2/7) or become (1/8) slowly proliferating than for patients whose tumors had remained (5/7) or become (4/4) rapidly proliferating.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Cytochemically unreactive neutrophils from subjects with myeloperoxidase (MPO) deficiency show a complex pattern of immunoreactivity with anti-MPO monoclonal antibodies: a flow cytometric and immunocytochemical study.

Neutrophil granulocytes from 12 subjects with primary myeloperoxidase (MPO) deficiency (six totally deficient) and 16 patients with secondary partial MPO deficiency were tested using two different anti-MPO antibodies, in combination with either a flow-cytometric technique or an immunoalkaline phosphatase staining method. Results demonstrated three different cytofluorimetric patterns of immunoreactivity with the MPO protein: (a) a bright MPO antigenic expression, typical of patients with secondary MPO deficiency (comparable to that observed in the control group); (b) a medium MPO antigenic expression, typical of subjects with primary partial MPO deficiency; and (c) a dim MPO antigenic expression, characteristic of individuals with hereditary total MPO deficiency. No significant differences in granulocyte MPO reactivity were demonstrated for the two antibodies. Furthermore, in two individuals with complete primary enzyme deficiency, the single histogram analysis of MPO fluorescence determined by flow cytometry seemed to show that only 38% (case 1) and 44% (case 2) of neutrophils were reactive with the anti-MPO antibodies: the use of multiple histogram analysis in combination with Kolmogorov-Smirnov statistics allowed us to demonstrated that all the cells express a low density of MPO antigen. These data were more or less confirmed by the APAAP labeling method, which showed a reduced straining only in subjects with primary deficiency, while all patients with secondary deficiency had scores similar to those observed in controls (healthy subjects). Compared with the immunoenzymatic technique, the flow-cytometric procedure showed a higher sensitivity to MPO, being able to estimate even minor decreases in neutrophil MPO antigenic expression, as previously postulated by other authors. This work suggests that patients with primary MPO deficiency have different amounts of MPO antigens in the neutrophil granulocytes, and the levels of MPO fluorescence seem to decline concurrently with the enzyme activity, thereby suggesting the presence of a diminished MPO production. In contrast, the normal antigenic reactivity of neutrophils from patients with acquired MPO deficiency indicates the presence of a functionally inactive form of the enzyme.

Antibodies, Monoclonal↗
PubMed1991

Two simple indexes used to evaluate the impact of therapy on the quality of life of patients receiving primary chemotherapy for operable breast cancer.

The psychometric characteristics of two indexes used to evaluate the subjective morbidity of chemotherapy regimens were analyzed. Both indexes assessed the duration of discomfort as perceived by the patient throughout therapy. The first index asked patients to state the number of days spent with 'discomfort', and the second index asked them which days they would like to eliminate altogether because of the unbearable symptoms experienced on those days. While the first index gives some idea of the duration of suffering, without defining it, the second highlights a specific time when the quality of her life was unacceptable to the patient. We studied these indexes in the form of a questionnaire completed by 168 women who had entered a cancer clinical trial. This trial evaluated the efficacy of primary chemotherapy in rendering conservative surgery feasible in women with operable breast cancer, but whose tumor size was greater than 3 cm. Four different treatment regimens were used: CMF, FAC, FEC, FNC (C = cyclophosphamide, M = methotrexate, F = fluorouracil, A = adriamycin, E = epirubicin, N = mitoxantrone). Seventy-nine patients were interviewed during chemotherapy and 89 during follow-up visits. Initial assessment of the reliability, discriminant and concurrent validity of the two indexes produced satisfactory results. Finally, we analyzed the responses given by 168 patients for a total of 600 treatment cycles. The average value of 'discomfort' was 3 days, whereas the average value of days 'to be eliminated' was 1. The range of subjective morbidity (for every cycle of treatment: 'discomfort = 0-30 days; 'to be eliminated' = 0-20 days) was very broad.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Cyclophosphamide, methotrexate, and fluorouracil with and without doxorubicin in the adjuvant treatment of resectable breast cancer with one to three positive axillary nodes.

In the attempt to improve current adjuvant results in patients with one to three positive axillary lymph nodes, in November 1981 we activated a prospective randomized study to assess the effectiveness of intravenous (IV) cyclophosphamide, methotrexate, and fluorouracil (CMF) for 12 courses versus CMF for eight courses followed by Adriamycin (doxorubicin; Farmitalia Carlo Erba, Milan, Italy) for four courses. The 5-year results were evaluated in a total of 486 patients entered into the study up to December 1987. CMF chemotherapy was delivered IV for a total of 12 courses when given alone and for eight courses when followed by four courses of Adriamycin. All drugs were recycled every 3 weeks. Rather than temporarily reducing doses, drug administration was delayed for 1 to 2 weeks in the face of myelosuppression on the planned day of treatment. After a median follow-up of 61 months, no significant differences were evident between the treatment groups in terms of relapse-free (CMF 74% v CMF followed by Adriamycin 72%) and total survival (CMF 89% v CMF followed by Adriamycin 86%). Drug treatments were fairly well tolerated and devoid of life-threatening toxicity. Present results, which were not influenced by menopausal status, indicate that Adriamycin given after CMF failed to improve treatment outcome over CMF alone. However, the role of Adriamycin in an adjuvant setting remains to be further clarified. Considering the good 5-year results achieved in this study at the expense of minimal toxicity, full-dose CMF remains, at present, the adjuvant chemotherapy of choice for patients with one to three positive nodes.

Adenocarcinoma↗
PubMed1991

[Cytofluorometric study of myeloperoxidase (MPO) expression in neutrophilic granulocytes of subjects with primary or secondary MPO deficiency: analysis of the histographic antigen distribution using the Kolmogorov-Smirnov mathematical model].

Neutrophil granulocytes from 12 subjects with primitive myeloperoxidase (MPO) deficiency (6 totally deficient) and 16 patients with secondary partial MPO deficiency were tested using two different anti-MPO monoclonal antibodies (MoAbs), in combination with a flow cytometer. Results demonstrated three different patterns of immunoreactivity with the MPO protein:i) a bright MPO antigenic expression, typical of patients with secondary MPO deficiency (comparable with that observed in the control group); ii) a medium MPO antigenic expression, typical of subjects with hereditary partial MPO deficiency; and iii) a dim MPO antigenic expression, characteristic of individuals with hereditary total MPO deficiency. No significant differences in granulocyte MPO reactivity were demonstrated for the two MoAbs. Furthermore, in two individuals with complete primitive deficiency, the single histogram analysis of MPO fluorescence seemed to show that only 38% (case 1) and 44% (case 2) of neutrophil were reactive with the MoAbs anti-MPO: the use of multiple histogram analysis in combination with Kolmogorov-Smirnov statistics allowed us to demonstrate that all the cells express a low density of MPO antigen. These data suggest that patients with primary MPO deficiency have different amount of MPO antigens in the neutrophils, and the levels of MPO fluorescence seem to decline concurrently with enzyme activity, thereby suggesting the presence of a diminished MPO production. On the contrary, in most cases of acquired MPO deficit, the reduced cytochemical activity contrasts with normal antigenic reactivity: this might be the result of the presence of an inactive enzyme.

Antibodies, Monoclonal↗