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Biomedical subjects

E Ascari

Publications and source records attributed to E Ascari.

At least 91 records · Page 5Linked to original sources
PubMed1990

Relevance of class, molecular weight and isoelectric point in predicting human light chain amyloidogenicity.

The ability to predict the amyloidogenicity of certain light chains may facilitate an earlier diagnosis of AL amyloidosis and, possibly, lead to more effective treatment. Using current methods, available in clinical chemistry laboratories, we assessed the class, the relative molecular mass (Mr) and the isoelectric point of urinary monoclonal light chains from 35 patients with AL amyloidosis (A+) and 51 without amyloidosis (A-). The light chain class (LCC) was lambda in 77% and 45% of A+ and A- patients, respectively. Light chain fragments (LCF) with low Mr (12-18 x 10(3) were detected in the urine of 30/35 A+ patients and in 15/51 A- ones. The mean (SD) isoelectric point (pI) of A+ light chains was 4.8 (1.1) while in A- patients it was 6.2 (1.6). Univariate analysis showed significant differences between the two groups for the three parameters. Discriminant analysis gave a function which allowed a correct allocation of 81% of the cases between the two groups.

Amyloidosis↗
PubMed1990

Induction and maintenance alpha-interferon therapy in myelofibrosis with myeloid metaplasia.

In 12 patients having myelofibrosis with myeloid metaplasia (MMM), recombinant- alpha interferon (r-alpha INF) was given for 16 weeks at an initial dose of 3 x 10(6) U/day as a cytoreductive agent. At the end of the 16th wk, Hb showed minor changes; WBC were reduced from 43 x 10(9)/l, range 6.4-69.4, to 16 x 10(9)/l, range 5-39 (p = 0.05); platelets decreased from 845 x 10(9)/l, range 215-1748, to 370 x 10(9)/l, range 96-730 (p = 0.005). 2 cases responded at the starting dose, while the effective dose was 5 x 10(6) U/d in the others. Minor changes in spleen size were noted, while no significant changes in bone marrow fibrosis occurred. After induction therapy, 3 patients were allocated to maintenance therapy (from 10 up to 34 months). To maintain platelet count lower than 500 x 10(9)/l, the required r-alpha-INF dose was constantly 10 MU/wk, while the same result was not achieved in 1 case with hydroxyurea, 1 g/die. The association with hydroxyurea, 500 mg/die, allowed reduction of the r-alpha INF dose to 6 MU/die in 1 other case.

Adult↗
PubMed1990

Bone marrow biopsy in monoclonal gammopathies: correlations between pathological findings and clinical data. The Cooperative Group for Study and Treatment of Multiple Myeloma.

Between January 1987 and October 1989, 561 consecutive untreated patients with monoclonal gammopathy of undetermined clinical importance (MGUS) (n = 295) or with multiple myeloma (n = 266) were evaluated in a multicentre trial. Both bone marrow biopsy and aspiration (performed at different anatomical sites) were required at presentation. Bone marrow biopsy data indicated that changes in bone marrow composition from MGUS to early multiple myeloma and to advanced multiple myeloma followed a precise pattern, including an increased percentage of bone marrow plasma cells (BMPC%), a shift from plasmocytic to plasmoblastic cytology, an increase in bone marrow cellularity and fibrosis, a change in bone marrow infiltration (becoming diffuse rather than interstitial), a decrease in residual haemopoiesis and an increase in osteoclasts. In multiple myeloma the BMPC% of biopsy specimens and aspirate were closely related, although in 5% of cases the difference between the two values was greater than 20%. Some histological features were remarkably associated with each other. For example, BMPC% was higher in cases with plasmoblastic cytology, heavy fibrosis, or reduced residual haemopoiesis. Anaemia was the clinical characteristic most influenced by bone marrow histology. The BMPC% was the only histological variable which affected the greatest number of clinical and laboratory characteristics, including, besides haemoglobin concentration, erythrocyte sedimentation rate, radiographic skeletal bone disease, and serum concentrations of monoclonal component, calcium, beta 2-microglobulin and thymidine kinase activity. These data indicate that comparative bone marrow histology in monoclonal gammopathies has clinical importance.

Aged↗
PubMed1989

Cytoreductive effect of recombinant alpha interferon in patients with myelofibrosis with myeloid metaplasia.

In an attempt to reduce myeloproliferation, we administered recombinant alpha-2b interferon (r-alpha INF) to ten patients with myelofibrosis with myeloid metaplasia (MMM) in a hypercellular phase, as part of a phase II trial. Two patients experienced severe side effects and stopped treatment before completion of the first week. In the eight evaluable patients, r-alpha INF was given for 16 weeks at an initial dosage of 3 X 10(6) U/day, with monthly increments in the case of response failure, i.e. a decrease in WBC or platelet count of less than 25% of the initial value. Two cases responded at the starting dosage, while the effective dosage was 5 X 10(6) U/day in the others. At the end of the 16th week, Hb showed minor changes: from an initial value of 12.08 g/dl, range 8.3-17.3, to 11.6 g/dl, range 7.7-18 (P = 0.12); WBC were reduced from 54 X 10(9)/l, range 6.4-69.4, to 17.5 X 10(9)/l, range 5-39 (P = 0.09, 4/8 responses); platelets decreased from 775 X 10(9)/l, range 215-1748, to 403 X 10(9)/l, range 118-730 (P = 0.008, 8/8 responses). Minor changes in spleen size were also noted, while no significant changes in bone marrow fibrosis occurred. Influenza-like symptoms and fatigue were common side effects. In conclusion, r-alpha INF has a role as a non-leukemogenic cytoreductive agent in the therapy of MMM, especially for cases with thrombocytosis.

Adult↗
PubMed1989

Ploidy and proliferative activity measurement by flow cytometry in non-Hodgkin's lymphomas. Do speculative aspects prevail over clinical ones?

Paraffin-embedded lymph node biopsies from 107 patients with newly diagnosed non-Hodgkin's lymphomas were examined for cell DNA content and proliferative activity (as percentage of S-phase cells) by means of flow cytometry. Patients were diagnosed between 1975 and 1985 and were homogeneously treated according to the grade of histologic malignancy. Cytofluorimetric data were studied with regard to their correlation with histology (classified and reviewed according to both Kiel and Working Formulation criteria), clinical stage, presence of constitutional symptoms, presence of bulky disease, sex, age, and the following laboratory data measured at diagnosis: erythrocyte sedimentation rate, hemoglobin, serum lactic dehydrogenase and serum albumin concentration. Aneuploidy was more frequent in the high grade malignant subtypes and in the miscellaneous group but showed no correlations with the other clinical parameters studied. Proliferative activity demonstrated a wide variation of data but a trend was evident toward higher proliferative values in the more severe histologic subtypes. The survival discrimination allowed by high- and low-grade malignant histology is exactly reproduced when highly and slowly proliferating lymphomas are considered (greater than or less than or equal to 12% of S-phase cells). These results, analyzed with those in the literature, suggest that measurements of ploidy and proliferative activity add little independent information to what is already provided by current histologic classifications, mainly as far as clinical evaluation and prognosis are concerned. Cytokinetic-aided therapeutic choices can be usefully proposed in a restricted number of cases. Improvement of the available lymphoma classifications through a better integration of ploidy and cytokinetic data with immunologic, genetic and histologic findings is still an object to be pursued in cytometric studies.

Adolescent↗
PubMed1989

Study of three patients with monoclonal gammopathies and 'lupus-like' anticoagulants.

In three patients with monoclonal gammopathies: a case of multiple myeloma, a case of monoclonal gammopathy of uncertain significance (MGUS) and a case of monoclonal gammopathy associated with lymphocytic lymphoma, we found the presence of a circulating lupus-like anticoagulant. Coagulative studies showed that the paraproteins: an IgG3k, an IgG1k and an IgMlambda, were responsible for the anticoagulant activity by interacting with the thromboplastin phospholipids. Using isoelectrofocusing we demonstrated that the three monoclonal immunoglobulins had a strong basic charge which may have contributed to determining their interaction with the acidic thromboplastin phospholipids. The binding of various phospholipids to the monoclonal proteins was assessed by the fluorescence quenching method which showed heterogeneous specificity. In order to establish whether the electrical charge is also relevant in cases with polyclonal lupus anticoagulant, the polyclonal immunoglobulins were fractionated according to their charge. The strongest inhibitor activity was found in the most basic immunoglobulins. Monoclonal lupus-like anticoagulants represent useful tools for investigating the heterogeneous world of polyclonal lupus-like anticoagulants.

Aged↗
PubMed1989

The Merlini, Waldenström, Jayakar staging system revisited.

At present, none of the routinely used staging systems is entirely satisfactory, since all of them require some reconsideration to account for the most recent prognostic factors. Among these, serum beta-2 microglobulin (S-beta-2M) has proved to be a powerful prognostic test assessable in most centers. In order to improve the Merlini, Waldenström, Jayakar (MWJ) staging system, we have determined the prognostic significance of several factors in an independent population of 345 retrospective myeloma patients seen at our institution from 1973 to 1988. The Cox regression hazards method showed that S-Creatinine, S-Albumin levels and percentage of bone marrow plasma cells accounted for 94% of total chi 2 achieved with all eight variables (including also: paraprotein index, S-Calcium, S-M-component, bone lesions and hemoglobin). The same analysis, applied to patients in whom S-beta-2M was available at presentation, selected S-beta-2M, S-Creatinine and percentage of bone marrow plasma cells (accounting for 92% of total chi 2), followed by platelet count, S-Albumin and S-M-component. The best discriminatory level of S-beta-2M was found to be 4 mg/l. However, the prognostic power of S-beta-2M when used with binary values was remarkably reduced with respect to its application as a continuous variable. In patients with MWJ stage 1 and 2 disease, S-beta-2M had an independent prognostic significance. Grouping stage I and II patients with S-beta-2M less than or more than 4 mg/l presented a median survival of 70 and 40 months, respectively. In stage 3 patients S-beta-2M did not contribute additional prognostic information.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Treatment of painful bone lesions and hypercalcemia.

The control of myeloma bone disease has been an important therapeutic problem. Bisphosphonates are potentially active for the control of myeloma bone resorption. Although several studies proved the efficacy of short-term bisphosphonate treatment in inhibiting myeloma bone destruction, data on the long-term efficacy are scanty. We present the results of a prospective pilot study for the evaluation of long-term parenteral administration of dichloromethylene bisphosphonate (Clodronate) in 30 patients with active myeloma bone disease. Patients were treated with a mean of 4 courses (range 2-8) of Clodronate: 300 mg/d i.v. for 7 days followed by 100 mg/d i.m. for 10 d, administered at a mean interval of 4 months. The median follow-up was 24 months (range 8-36). Clodronate reduced bone pain rapidly and significantly, and reduced the mean values of the biochemical indices of bone resorption to within normal limits. The occurrence of skeletal morbidity in patients treated with Clodronate was compared with that observed in the control group of myeloma patients treated with chemotherapy only: Clodronate provided a significant (p less than 0.001) reduction in severe bone pain as well as in the incidence of new osteolytic lesions and pathological fractures. The results of this prospective pilot trial indicate that supportive long-term treatment with parenteral Clodronate can contribute significantly to controlling the progression of myeloma bone disease.

Bone Diseases↗
PubMed1989

Increasing interdependency of prognosis- and therapy-related factors in Hodgkin's disease.

Two subsequent series of patients with Hodgkin's disease (HD) treated according to different therapeutic plans were compared: the study made it possible to analyze the role played by therapy in influencing the individual importance of a group of well-known prognostic factors. Study 1 concerned 667 patients treated in the period 1971-1979 without special measures for mediastinal bulky disease and with four-drug chemotherapy regimens (MOPP, COPP, ABVD) for stage B or IV. Study 2 included 220 patients treated between 1980 and 1984 with combined sandwich chemoradiotherapy when mediastinal bulk was present, and with eight-drug alternating chemotherapy regimens for stages B or IV (MOPP/ABVD, CcVPP/ABVD). Distribution of epidemiologic and clinical characteristics as well as staging accuracy were comparable in the two series. Only sex, serum albumin at onset and success or failure in achieving complete remission showed the same ability to discriminate survival in both studies. Age, stage and histology retained a reduced role in Study 2, where it was found they could be handled as binary variables, i.e. more or less than 50 years of age, stage IV or other stages, lymphocyte depletion histotype or other types. The influence of B symptoms on survival was sharply decreased in patients treated with alternating chemotherapy regimens, whereas combined sandwich therapy showed a truly leveling effect on the role of mediastinal bulk, which has to be considered a very unfavorable factor with other treatments. In HD the evaluation of clinical findings with respect to their impact on prognosis is crucial for validating and graduating the staging process, and for matching the intensity of the therapy to the needs of the patient. The ongoing evolution in the roles of single prognostic factors due to therapy needs periodic reevaluation for proper adjustments of therapeutic strategies.

Adolescent↗
PubMed1989

Isolation of Reed-Sternberg cells from lymph nodes of Hodgkin's disease patients.

This study describes a simple and relatively rapid method of purifying Reed-Sternberg (R-S) cells and their morphologic variants from the lymph nodes of patients affected by Hodgkin's disease. Our initial studies defined the optimal procedure for a quantitative disaggregation of Hodgkin's lymph nodes and the densities of R-S cells in several donors. These preliminary steps were helpful in the development of strategies for selectively concentrating R-S cells by density gradient centrifugation. We layered a single-cell suspension over Percoll of appropriate density, centrifuged these samples for 15 minutes, and collected a fraction enriched in R-S cells. Most of the R-S cells were distributed between densities of 1.060 and 1.072, with a peak at approximately 1.066 g/mL. R-S cells are denser than many mononuclear cells present in the lymph nodes of Hodgkin's patients and lighter than reactive cells such as eosinophils, mast cells, and neutrophils. However, the ranges of densities of these cell types overlap, making purification of R-S cells by isopyknic centrifugation impossible. Nevertheless, when this enriched fraction is further processed by velocity sedimentation in order to take advantage of the larger size of R-S cells as compared with all other cells, a substantial purification is achieved. We used three different velocity-sedimentation chambers to find the optimal conditions for obtaining the highest purity with a high final yield. The cells isolated by this method are viable, appear to be morphologically normal, and have been further characterized biologically.

Antigens, Surface↗
PubMed1989

Effects of desferrioxamine on normal and leukemic human hematopoietic cell growth: in vitro and in vivo studies.

The iron chelator desferrioxamine (DFO) has been previously shown to be an S-phase inhibitor of cell proliferation. To investigate its potential as an antileukemic drug, we first studied the effects of DFO on the in vitro growth of normal human hematopoietic progenitors (CFU-GM and BFU-E) and clonogenic cells from human leukemic cell lines. Then we evaluated the effects of DFO on progression of leukemia refractory to conventional therapy in two individuals. Micromolar concentrations of DFO determined a dose-dependent inhibition of normal progenitor growth, with inhibitory dose 50% (ID50) for CFU-GM and BFU-E being 6.7 and 5.5 microM/liter, respectively. Marked inhibitory effects were observed on clonogenic cells from HL-60 (ID50 = 1.4 microM/liter) and U-937 (ID50 = 3.6 microM/liter) human leukemic cell lines grown in semisolid medium. When DFO was given intravenously to a patient with lymphoid blast crisis of chronic myelogenous leukemia, a marked reduction in circulating blast count was observed. On the contrary, no in vivo effect was observed in a patient with acute nonlymphocytic leukemia having transfusional iron overload. We conclude that: (a) DFO is an inhibitor of both normal and leukemic myeloid cell proliferation in vitro; (b) our limited in vivo observations and a previous case study suggest that intravenous administration of DFO to patients with normal to low plasma iron may result in leukemic cytoreduction in vivo.

Anemia, Refractory, with Excess of Blasts↗
PubMed1988

Cell kinetics in human malignancies studied with in vivo administration of bromodeoxyuridine and flow cytometry.

Bromodeoxyuridine (BrdUrd) is a pyrimidine analogue which is incorporated into the DNA of proliferating cells. When in vivo BrdUrd infusion is coupled with bivariate flow cytometry to measure cell BrdUrd incorporation and DNA content, both the percentage of DNA-synthesizing cells [BrdUrd-labeling index (LI)] and the DNA synthesis time (TS) can be determined on the same tissue sample. From experimentally determined LI and TS, the potential doubling time of the population and its cell production rate are calculated. To ascertain whether the BrdUrd infusion method is clinically feasible and if data are reliable, we studied patients with leukemia, refractory anemia, multiple myeloma, and brain and gastric tumors. The BrdUrd incorporation data were compared with those determined on duplicate samples with the techniques conventionally used for LI and TS values, i.e., 3H- and 14C-labeled thymidine autoradiography, respectively. The complete BrdUrd procedure takes 6-9 h, and no immediate toxicity from BrdUrd administration has been observed. In an 8-month period, 154 patients were studied. Successful LI and TS determinations were obtained in 78.9 and 59.7% of cases, respectively, more often in hematological than in solid tumors. The values for LI and TS assessed with the BrdUrd technique were very close to those found with 3H- and 14C-labeled thymidine autoradiography (r = 0.88, P less than 0.005, and r = 0.89; P less than 0.005, respectively). The potential doubling time and production rate were accordingly similar. These data indicate that in vivo BrdUrd infusion coupled with flow cytometry measurements can be performed in clinical settings and that this method is reliable. It could be used for kinetic studies in clinical trials aimed at evaluating the prognostic relevance of proliferative parameters and for planning radio- and/or chemotherapy.

Autoradiography↗
PubMed1988

Hodgkin's disease prognosis: a directly predictive equation.

586 patients with Hodgkin's disease diagnosed between 1970 and 1979 were staged and treated in the same way. Multivariate analysis was used to delineate the prognostic roles of several clinical features at diagnosis. A multiple regression analysis was applied to an exponential model for survival-time distribution, which proved to fit the data accurately. Several clinical characteristics were studied and those that could singly discriminate survival significantly were chosen as predictive variables for the multiple regression. These were: sex, age, stage, histological subtype, presence of constitutional symptoms, mediastinal mass, and erythrocyte sedimentation rate (ESR), and haemoglobin and serum albumin concentrations. ESR, stage, histological subtype, and age proved to be the best prognostic factors, while sex and albumin had minor value. The presence of symptoms, mediastinal bulk, and haemoglobin were not so important. A linear equation for the six variables was derived to calculate the estimated median survival time for any given patient. This equation was validated on an external group of 179 similar patients.

Actuarial Analysis↗
PubMed1988

Cell cycle-related proteins: a flow cytofluorometric study in human tumors.

We used 2-parameter flow cytometry (FCM) to investigate the relationship between the cell cycle phases and 3 proteins whose expression is known to increase in proliferating cells: the surface antigen transferrin receptor (Trf-r), the "cyclin" (a proliferating cell nuclear antigen, PCNA), and the nuclear antigen recognized by the monoclonal antibody (MoAb) Ki-67. FITC-labeled antibodies against Trf-r, PCNA, and the Ki-67-reactive antigen, as well as propidium iodide-DNA distribution, were simultaneously measured on human leukemia HL-60 and K562, and breast carcinoma MCF-7 cell lines and on fresh human leukemic and glioblastoma cells. The 70% ethanol fixation for Trf-r and PCNA and the 95% acetone fixation for Ki-67 plus permeabilization (with 0.1% and 1% Triton X100, respectively, for the surface and the nuclear antigens) produced cell suspensions with negligible cell clumping, high-quality DNA profiles, and bright specific immunofluorescent staining. The investigated proteins have different relationships with the proliferative state of the cell. Trf-r is expressed mainly at the transition from G0/G1 to S-phase. PCNA expression is prominent in late G1 and through S-phase and decreases in G2-M. The Ki-67-reactive antigen is widely distributed in G1, S, and G2-M phases. Knowledge regarding the relationships between proliferation-associated antigens and cell cycle phase in normal and neoplastic cells could improve our understanding of the mechanisms underlying growth regulation and neoplastic transformation. Bivariate FCM is an easy method for obtaining these data from large numbers of cells.

Antibodies, Monoclonal↗
PubMed1988

A prognostic classification of myelofibrosis with myeloid metaplasia.

The dependence of survival time on a set of prognostic factors was explored by means of Cox's regression model in 137 cases of myelofibrosis with myeloid metaplasia (MMM). The following parameters recorded at diagnosis proved to be important independent indicators of a poor prognosis: a higher value for age, a lower value for Hb concentration, a higher value for immature myeloid cells in peripheral blood (IMC), a lower value for total erythroid iron turnover (TEIT), and a bone marrow red cell aplasia (RCA). A prognostic classification tree was constructed whose terminal nodes (risk groups), described by simple logical conditions upon important indicators, were characterized by significantly different expected survival. The two extreme risk groups lend themselves to a simple, but complete description. The low-risk group (19.7% of the sample) comprises cases who had the diagnosis of MMM before age 45 and a number of IMC constantly lower than 24%. The actuarial proportion of patients surviving at 15 years was 100%. The high-risk group (29.9% of cases) comprises patients with age greater than 45 and Hb lower than 13 g/dl, associated with RCA, or with a relatively decreased erythropoiesis (TEIT lower than 2 times the normal) or with IMC greater than 24%. Seven out of the 11 who died within this group developed blastic crisis. Median survival time of the group was 69 months.

Adolescent↗