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Biomedical subjects

F Grignani

Publications and source records attributed to F Grignani.

At least 127 records · Page 7Linked to original sources
PubMed1988

Low-dose mitomycin and weekly low-dose doxorubicin combination chemotherapy for patients with metastatic breast carcinoma previously treated with cyclophosphamide, methotrexate, and 5-fluorouracil.

Forty-four evaluable patients with breast carcinoma previously treated with combination chemotherapy consisting of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) were treated with a combination chemotherapy regimen consisting of doxorubicin (A) (20 mg/m2 on days 1, 8, 15, and 22, repeated every 28 days) and mitomycin (MIT) (10 mg/m2 on day 1, repeated every 28 days). Five patients (11%) achieved a complete remission (CR) and 14 patients (32%) had a partial response (PR). The median duration of survival was 11.5 months and the median duration of response was 8 months for responders (CR and PR). Toxicity was moderate and consisted of neutropenia (74%), thrombocytopenia (25%), pneumonitis (11%), and cardiomyopathy (2%). The combination chemotherapy regimen A and MIT is an effective regimen for treating previously treated with CMF.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

A randomized trial to evaluate the immunorestorative properties of thymostimulin in patients with Hodgkin's disease in complete remission.

A total of 19 Hodgkin's disease (HD) patients (12 male, 7 female) aged 26-67 years, who had been in complete unmaintained remission for 6 months or more when the study was initiated, were randomly given 50 mg thymostimulin (TS) i.m. daily (G1) or every other day (G2) for 35 days. A third group (G3) was not treated. Then TS, at the same dose was administered twice a week for the following 22 weeks in patients both initially receiving loading or intermittent TS treatment. When compared with age- and sex-matched controls, as a group, the patients' circulating OKT3+, OKT4+, OKT11+ and E-AETR+ cells were depressed (P less than 0.001 for both proportions and absolute numbers), whereas their OKT8+ cell population was not. Following 5 weeks of daily TS administration, the proportions and numbers of all T cell fractions significantly increased in G1 patients (P less than 0.03 for all the comparisons tested), while following intermittent TS treatment (G2) only the proportions of OKT3+ and OKT11+ cells (P less than 0.03), but not of other T cell fractions, significantly increased. In addition, no significant changes in the absolute numbers of T cell fractions were observed in this group of patients. Furthermore, no spontaneous variations in the T cell pool size occurred in untreated patients. TS maintenance therapy did not produce any further improvement in the size of overall T cells and T cell subsets but sustained percentage and absolute numbers of these cells during administration and the absolute number of T cells even after discontinuation of therapy. The TS-induced improvement in the T cell pool was not associated with any change in the size of circulating non-T lymphocytes and monocytes. In vitro phytohemagglutinin-induced interleukin-2 (IL-2) and gamma-interferon (IFN-gamma) synthesis was assessed in 11 patients (3 G1, 4 G2, and 4 G3). Although it was not statistically significant, a rise in IL-2 and IFN-gamma production was observed in TS-treated patients, but not in untreated controls. TS failed to exert any effect on the serum circulating levels of neopterin, type I and II IFN, beta-2 microglobulin (B2-M) and immunoglobulins (Ig). TS can thus improve defective T cell frequences and numbers and may modulate IL-2 and IFN-gamma production.

Adjuvants, Immunologic↗
PubMed1988

5q- syndrome terminating in acute myeloid leukemia. Karyotype evolution and immunologic characterization of blast cells.

We report a case of 5q- syndrome that progressed to acute nonlymphocytic leukemia after 9 years of clinically and morphologically stable disease. The transition from the chronic to the leukemic phase was characterized by the appearance of an additional cytogenetic anomaly [inv(2)] in the cell carrying the 5q-, together with the expansion of a clone showing an apparently normal karyotype.

Anemia, Refractory↗
PubMed1988

Phase III randomized study of fluorouracil, epirubicin, and cyclophosphamide v fluorouracil, doxorubicin, and cyclophosphamide in advanced breast cancer: an Italian multicentre trial.

From February 1983 to January 1985, 497 patients with advanced breast cancer were randomly allocated to receive either epirubicin or doxorubicin in the following combination chemotherapy regimen: fluorouracil (5-FU) 500 mg/m2 intravenous (IV) on days 1 and 8; epirubicin or doxorubicin 50 mg/m2 IV on day 1; cyclophosphamide 500 mg/m2 IV on day 1 (FEC or FAC). Cycles were repeated every 21 days until progression or to cumulative doses of 700 mg/m2 for epirubicin and 550 mg/m2 for doxorubicin. Dose reductions were applied according to the standard criteria. Activity was evaluated in 443 patients (222 in the FEC arm and 221 in the FAC arm). The two experimental groups were comparable in age, performance status, menopausal status, histology, previous treatments, and site of the disease. The overall response rate (complete response and partial response [CR + PR]) was not significantly different: 53.6% for FEC and 56.5% for FAC. The median time to progression was 273 days for FEC and 314 days for FAC; the median survival time was 591 and 613 days, respectively. Leukopenia, anemia, nausea, and vomiting were significantly lower in patients treated with FEC. As for cardiotoxicity, four cases of congestive heart failure (CHF) were recorded among patients treated with FAC while only one was observed in the FEC group. These results indicate that epirubicin in a combination chemotherapy regimen is as active as doxorubicin and is significantly less toxic.

Adult↗
PubMed1988

Imbalances within the peripheral blood T-helper (CD4+) and T-suppressor (CD8+) cell populations in the reconstitution phase after human bone marrow transplantation.

Peripheral blood T cell subsets were evaluated in 11 patients during the reconstitution phase after allogeneic bone marrow transplantation and compared with 11 age-matched controls. The proportion of cells coexpressing Leu7 and CD11b (C3bi receptor) markers was determined within the CD4+ (T-helper) and the CD8+ (T-suppressor) subsets by two-color immunofluorescence analysis. CD4+ and CD8+ T cells reached normal or near-normal values within the first year posttransplant. In contrast to normal controls, however, most of the cells in both subsets coexpressed the Leu7 and CD11b markers. T cells with such phenotype display the morphological features of granular lymphocytes (GLs) and a functional inability to produce interleukin 2 (IL 2). These T cell imbalances were not related to graft v host disease (GvHD) or to clinically detectable virus infections and may account for some defects of cellular and humoral immunity that occur after bone marrow transplantation.

Adolescent↗
PubMed1988

Imipenem/cilastatin in the treatment of severe hospital infections.

Imipenem/cilastatin as a single agent or in combination with amikacin was used as empirical treatment of severe hospital infections. Twenty-five patients were evaluable for efficacy and the overall response rate was 62% with imipenem/cilastatin alone and 80% with imipenem/cilastatin in combination with amikacin. The highest response rate was obtained in urinary tract infection (75%) and in pneumonia (70%) and the lowest response rate (50%) was observed in bacteremia of unknown origin and in skin and soft tissue infections. Eight failures were observed and seven of them occurred in patients treated with imipenem/cilastatin alone. Two deaths occurred, both in patients with bacteremia. Imipenem/cilastatin treatment was interrupted early in 3 patients because the pathogen developed resistance during therapy and in 2 other patients because of side effects. In our study imipenem/cilastatin proved to be efficacious and well tolerated. The addition of an aminoglycoside to imipenem/cilastatin might improve its efficacy and prevent pathogens from becoming resistant during therapy. Therefore this association would seem to be advisable for the therapy of bacteremic infections and for those caused by difficult pathogens.

Adult↗
PubMed1988

Interferon alpha-2b as therapy for Ph'-positive chronic myelogenous leukemia: a study of 82 patients treated with intermittent or daily administration.

The authors treated a total of 82 patients with Ph'-positive chronic myelogenous leukemia (CML) with recombinant interferon alpha-2b (IFN alpha-2b). Sixty-five patients in chronic phase (CP), 28 of whom were untreated and 37 pretreated, and nine patients in accelerated phase (AP), were started on IFN three times a week. Patients in CP were randomized to receive 2 or 5 X 10(6) IU/m2, while patients in AP were all given the dose of 5 X 10(6) IU/m2, in addition to concomitant chemotherapy. Patients in CP who were unresponsive to the lower dose were crossed to the higher dose. Of 63 evaluable patients in CP, 43 (68%) responded, 29 (46%) achieved complete hematologic response (CHR), and 14 (22%) achieved partial hematologic response (PHR). The response rate appeared to be significantly influenced by the IFN dose in pretreated patients. Of the nine patients in AP, two attained PHR and one CHR. More recently, eight previously untreated CP cases were submitted to daily IFN administration at doses from 2 to 5 X 10(6) IU/m2. This daily schedule was also applied to patients who had obtained, with the intermittent treatment, a PHR persisting unmodified for six months (nine patients) or an unstable CHR (five patients). Seven of the eight previously untreated patients, and five of the nine PHR patients crossed to daily IFN reached CHR. In the total series of previously untreated patients, the response rate proved to be significantly influenced by the initial risk status. Cytogenetic improvement was seen in 37 of 53 responders (70%) treated for more than 3 months, the median of Ph'-positive cells declining from 100% to 65% (range 0% to 95%). Complete suppression of Ph' chromosome was observed in one case. The cytogenetic response was persistent for over 6 months in 21 patients, but the lowest value of Ph' positivity was usually unstable. At a median follow-up of 56 weeks, 23 of 36 (64%) CHR patients remain in continued disease control with IFN. A blastic transformation (BT) occurred in seven of 21 unresponsive patients and in one of the 36 CHR patients. The authors' data confirm that IFN alpha-2b, especially at daily doses, is effective in inducing clinical and cytogenetic response in a good proportion of patients with CML in the benign phase. Longer follow-ups will define the exact influence of this agent on the natural course of the disease.

Adolescent↗
PubMed1988

Immunological and molecular studies in a case of follicular lymphoma with an extra chromosome 12 and t(2;8) translocation.

Two sequential lymph node biopsies taken from a non-Hodgkin lymphoma patient revealed two karyotype abnormalities peculiar to B cell neoplasias: trisomy 12 and t(2;8)(p12;q24) translocation. The first was documented in all cells analyzed, while the second was present in 20% of the metaphases from the first biopsy and in 100% from the second. This suggests that the t(2;8) translocation arose as a secondary karyotypic change. In addition, although immunological characterization of the neoplastic cells disclosed a monoclonal B cell population that expressed immunoglobulin kappa light chains, as usually found in Burkitt's lymphoma with t(2;8) translocation, Southern blot analysis provided evidence of rearrangement in only one kappa chain allele.

Chromosome Aberrations↗
PubMed1987

High frequency of clonal immunoglobulin or T cell receptor gene rearrangements in acute myelogenous leukemia expressing terminal deoxyribonucleotidyltransferase.

Ig and T cell receptor rearrangements have been used as irreversible markers of lineage and clonality in the study of B- and T-lymphoid populations. We have addressed the issue of lymphoid lineage specificity of these rearrangements by analyzing a panel of 25 TdT- acute myelogenous leukemias, 13 TdT+ AMLs, and 4 TdT+ undifferentiated leukemias. We report that while gene rearrangements represent extremely rare events in classical TdT- AML (less than 8%), rearrangements of either the Ig or T beta locus or both were detectable in the majority of the TdT+ AMLs (greater than 60%), and rearrangements of both loci were detectable in all of the TdT+ undifferentiated leukemias. These data demonstrate a significant association between TdT expression and Ig or T beta gene rearrangements even outside the lymphoid lineage, further supporting a role for TdT in Ig and T cell receptor gene assembly. These data also indicate that a coordinated program of lymphoid gene expression involving TdT-CD7-expression and Ig/T beta rearrangements can be activated before myeloid commitment. Whether the activation of this program represents a normal, albeit rare, event in early myelopoiesis or a transformation-related event present only in leukemic cells remains to be determined.

Cell Differentiation↗
PubMed1987

Thymic hormone modulation of CD38 (T10) antigen on human cord blood lymphocytes.

We studied the in vitro effect of three different thymic factors on the expression of CD38 (T10) antigen on cord T-lymphoid cell surface. The results showed that cord mononuclear cell populations contain variable percentages of CD38+ cells. The CD38 molecule was expressed on cord T and B lymphocyte and monocyte surfaces. Incubation with thymic agents induced a significant increases in the CD38+ cell percentage only in the samples with low CD38 antigen expression, and this modulation was mainly attributable to the T-cell subset. The effect seems to be specific and not correlated with the known high spontaneous DNA synthesis rate of cord mononuclear cells.

ADP-ribosyl Cyclase↗
PubMed1987

Expression of lymphoid-associated antigens on Hodgkin's and Reed-Sternberg cells of Hodgkin's disease. An immunocytochemical study on lymph node cytospins using monoclonal antibodies.

The aim of this study was to elucidate the origin of Hodgkin's and Reed-Sternberg cells. Lymph node cytospins and frozen sections from 20 cases of Hodgkin's disease of different histological subtypes were immunostained by the immuno-alkaline phosphatase technique using a panel of monoclonal antibodies. As expected, the Hodgkin's and Reed-Sternberg cells of all cases were positive for the CD30 (Ki-1), CD15 (hapten X) and CD25 (Tac) antigens. In eight cases, a variable percentage of typical Hodgkin's and Reed-Sternberg cells showed a clear-cut cytoplasmic and/or surface positivity for the T-cell-associated antigens CD3, CD5, CD6 and CD4 (seven cases) or CD8 (one case), but consistently lacked B-cell and macrophage-associated markers. The best visualization of T-cell antigens was obtained in cytocentrifuge preparations and in areas of lymph node frozen sections that had been infiltrated by clusters of Hodgkin's and Reed-Sternberg cells. In two cases of Hodgkin's disease (nodular sclerosis, mixed cellularity) the neoplastic cells weakly expressed the B-cell antigens CD19 and CD22, but not T-cell or macrophage-associated markers. In 10 cases, Hodgkin's and Reed-Sternberg cells were negative for all the lymphoid- and macrophage-associated antigens. These results suggest a lymphoid (either T or B) rather than histiocytic origin for the Hodgkin's and Reed-Sternberg cells in a number of Hodgkin's disease cases.

Antibodies, Monoclonal↗
PubMed1987

Thyroid function tests in patients undergoing maintenance dialysis: characterization of the 'low-T4 syndrome' in subjects on regular hemodialysis and continuous ambulatory peritoneal dialysis.

Thyroid function tests were evaluated in 38 patients on regular hemodialysis (HD), in 36 on continuous ambulatory peritoneal dialysis (CAPD) and in 39 healthy controls. A significant reduction in total thyroxine (TT4), total triiodothyronine (TT3), reverse (rT3), and free T4 (fT4) mean levels and normal TSH, free T3, TBG and albumin concentrations was found in both HD and CAPD patients. A 'low-T4 syndrome' (serum T4 less than 5 micrograms/dl) was found in 9 CAPD (25%) and 20 HD (53%) patients, but none of them had fT4 levels below the normal laboratory range. The only striking difference between low-T4 HD and low-T4 CAPD patients was the significantly lower TBG and albumin serum levels in CAPD group. Low-T4 HD displayed normal TBG levels but enhanced fT4/TT4 and fT4/TT4 X TBG ratios. We concluded that: the abnormalities in thyroid function tests in patients on long-term dialysis (HD and CAPD) do not express the existence of a true hypothyroidism; a different pathogenesis of the low-T4 syndrome in the CAPD and HD groups may be hypothesized: in the former it could be attributed to a reduction in serum-binding capacity for thyroid hormones, in the latter the relative increase in fT4 percentage despite normal TBG levels suggests either the presence of T4-TBG-binding inhibitor(s), or structural abnormalities of thyroid-hormone-binding proteins.

Combined Modality Therapy↗
PubMed1987

Prognosis in chronic lymphocytic leukemia: a retrospective multicentric study from the GIMEMA group.

Clinical and biological data were evaluated using Desu univariate analyses or Cox multivariate analyses in a series of 1,777 chronic lymphocytic leukemia (CLL) patients from an Italian Cooperative Group. In univariate analyses, age and sex of patients, presence of bone marrow (BM; greater than or equal to 50%), and peripheral blood (PB; greater than or equal to 60,000/microL) lymphocytosis, anemia (hemoglobin [Hb] less than 11 g/dL), thrombocytopenia (less than 100,000/microL), direct Coombs' test positivity, hepatomegaly, splenomegaly, and extent of lymph node involvement were shown to be of significant prognostic value. Multivariate analyses, through a stepwise procedure, showed that the most important prognostic variables are Hb, hepatomegaly, lymph node involvement, PB lymphocytosis, and age and sex of patients. Further covariates would produce an improvement having a nonsignificant P value. Based on the results of multivariate analyses, a four-step staging using the significant variables of the Cox model is proposed.

Adult↗
PubMed1987

Immunoregulatory T cells in alcoholic liver disease: phenotypical dissection of circulating Leu3+/T4+ inducer T-lymphocytes.

Alcoholic liver disease (ALD) patients had normal absolute lymphocyte counts, increased percentage of Leu3+/T4+ cells (p less than 0.001) and raised T4/T8 ratio (p less than 0.01). Double-colour immunofluorescence analysis using isotype-specific goat anti-mouse immunoglobulins, fluorescein or rhodamine-conjugated, demonstrated that the rise in inducer (Leu3+/T4+) T-cells was almost entirely represented by an expanded population of T4+TQ1- and 5/9+ true helper lymphocytes. T4+ cells also expressed IL2 receptors, as detected by the anti-Tac monoclonal antibody (range 1-18%). On the other hand, the percentage of Leu3+/T4+ cells which bind the K562 cell-line or co-express NK markers on their surface, such as Leu7 (HNK-1), was within the normal range in the majority of ALD patients. Functional studies on patients' cultured total or B-enriched lymphocytes in a pokeweed-mitogen-driven B-cell differentiation assay showed an enhanced plasma cell generation even in unstimulated cultures. Co-culture experiments with normal enriched-B lymphocytes demonstrated that both irradiated and non-irradiated patient T cells led to an increased plasma cell generation. These findings indicate that helper T cells and B cells are all simultaneously activated in vivo, and that the suppressor T lymphocyte function is normal in ALD.

Adult↗
PubMed1986

Description of a sequential staining procedure for double immunoenzymatic staining of pairs of antigens using monoclonal antibodies.

This paper describes a sequential staining procedure for double immunoenzymatic staining of pairs of antigens in frozen tissue sections and cell smears using monoclonal antibodies. This technique involves performance of an indirect immunoperoxidase sandwich (including development of the enzyme reaction) followed by an unlabelled immuno-alkaline phosphatase sandwich (the APAAP method). The two enzyme labels are revealed using DAB/H2O2 for peroxidase and naphthol AS-MX plus fast blue or fast red for alkaline phosphatase. When compared with a hapten-sandwich/biotin-avidin system, the sequential staining procedure proved to be simpler and more sensitive and was also more suitable for double immunoenzymatic staining when monoclonal antibodies were only available in small amounts. The sequential staining procedure is particularly useful for the identification of antigens distributed in different cell populations or in different sites (e.g., nucleus and cytoplasm or cell surface) of the same cell. In contrast, this method does not appear to be very suitable for demonstrating two antigens located in the same site (e.g., surface membrane) of the same cell for which purpose double immunofluorescence remains the first choice.

Alkaline Phosphatase↗
PubMed1986

Cisplatin, etoposide, and mitomycin in the treatment of non-small cell carcinoma of the lung. A pilot study.

A total of 39 patients with non-small cell carcinoma of the lung (NSCL) were treated with cisplatin, etoposide, and mitomycin. A major response rate (complete response + partial response) was seen in 15 patients (39%). Median survival for all patients was 340 days; median survival of the responding group was 514 days. Toxic effects included moderate hematologic toxicity, nausea, and vomiting. There were no treatment-related deaths. This regimen clearly is effective in treating NSCL.

Adenocarcinoma↗
PubMed1986

Vindesine and mitomycin C in chemotherapy: refractory advanced breast cancer.

Thirty-five unselected postmenopausal women with metastatic breast carcinoma, refractory to hormonal manipulation and/or chemotherapy, were treated with vindesine (3 mg/m2 day 1, then weekly for 6 weeks, then every other week) and mitomycin (12 mg/m2 day 1, then every 6 weeks). Thirty-one patients were evaluable for response. Two patients obtained a complete response (CR), three patients a partial response. Duration of the response in the two patients with CR was 24 and 16 months, respectively. Toxicity was mild, consisting of leukopenia and neurologic toxicity. Thrombocytopenia was not a significant clinical problem. Vindesine with mitomycin C, as administered in this study, is a safe, but marginally effective regimen for previously treated patients with metastatic breast cancer.

Adult↗