Red cell ferritin as a diagnostic tool.
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Erythrocytes↗
Biomedical subjects
E Ascari
Publications and source records attributed to E Ascari.
Complete remission in plasma cell leukaemia.
Two patients with primary plasma cell leukaemia who achieved complete remission are reported. They were treated with induction therapy consisting of a multipeptide derivative of sarcolysin, Peptichemio, given intravenously, combined with vincristine and/or prednisone, followed by conventional melphalan-prednisone therapy. 5-7 months following the beginning of therapy, both patients attained a complete remission which lasted 23 and 6 months; second remission was not achieved. Survival from starting therapy was 57 and 16 months respectively. These cases indicate that intravenous alkylating agents can induce a complete remission in plasma cell leukaemia similar to that achieved in other acute leukaemias.
Aged↗
Role of tumor proteinases in tumor cell-induced platelet aggregation.
In a previous work we found a correlation between in vivo metastatic potential of cancer cells and their platelet aggregating activity in sublines of the mFS6 murine fibrosarcoma. In the present study the effects of different proteinase inhibitors on platelet aggregation induced by these cells were investigated. When the platelets were incubated with the inhibitors, only those effective against cysteine proteinases strongly reduced platelet aggregation by cancer cells; serine protease inhibitors, including hirudin, had no effect on platelet response. Incubation of neoplastic cells with the same inhibitors gave similar, though less evident results. Addition of neoplastic cells to platelet-rich plasma also caused significant production of fibrinopeptide A, more by the less malignant cells. Thus, in this experimental model a cysteine proteinase of the neoplastic cells appears to play an important role in the platelet aggregation induced by them, and this property was detected in the M4 cells with high metastatic in vivo activity.
Adult↗
Proliferative characteristics and ploidy of human brain tumors by DNA flow cytometry.
We studied nuclear DNA distribution by flow cytometry in 59 human brain tumors. Samples were frozen at -20 degrees C immediately after surgery and unicellular suspensions were obtained with a mechanical dissociation technique. Nuclear DNA was stained with propidium iodide. Normal human brain tissue was used as a diploid reference standard. In 86.3% of benign tumors an unimodal DNA distribution with a DNA index usually within the diploid range was found. Among malignant tumors, 64% had un unimodal DNA distribution with diploid or near-diploid modal DNA content. The remaining 36% showed an additional cell peak with a DNA index ranging from 1.15 to 1.92. The percentage of S-phase cells was higher in malignant (median = 3.8) than in benign tumors (median = 1.9) (p less than .001), without correlation to histological tumor subtype.
Aneuploidy↗
Immunological reactivity of serum ferritin in patients with malignancy.
Serum ferritin has been suggested as a tumor marker in the diagnosis of certain malignancies and for following the activity or dissemination of the malignant process. Since neoplastic tissues generally contain more acidic isoferritins than their normal tissue counterparts, it has also been suggested that the specific assay of such isoferritins in serum may be of particular value in the diagnosis of malignancy. In this work, we have evaluated ferritin concentration in the serum of normal subjects and patients with acute nonlymphocytic leukemia, Hodgkin's disease, breast cancer and lung cancer by simultaneously using three different immunoassays: an immunoradiometric assay based on polyclonal antibodies against human liver (basic, L-subunit rich) ferritin, a radioimmunoassay based on polyclonad antibodies against HeLa cell (acidic, H-subunit rich) ferritin, and an immunoradiometric assay based on the monoclonal antibody 2A4 raised against human heart (acidic, H-subunit rich) ferritin. Most of the patients studied had increased values for liver-type ferritin in the absence of increased iron stores. Binding of serum ferritin to concanavalin A did not prove to be useful in distinguishing a tumor-specific basic isoferritin. The HeLa ferritin assay was found to be less specific than the heart ferritin assay in the detection of acidic isoferritins, and did not provide any advantage over the liver assay in detecting the increased levels of serum ferritin associated with malignant disease. Heart-type ferritin was found in one-fifth of normal sera and 64% of sera from patients with malignancy. Values were very low compared with those for basic ferritin, ranging from less than 0.1 to 17% of total serum ferritin (geometric mean value 1.3%) in patients with malignancy. These findings indicate that at present there is little application for serum ferritin immunoassays based on antibodies to HeLa cell or heart ferritin in the diagnosis or monitoring of malignant disease. This seems to be due to the presence in human serum of biding factors which are responsible for the rapid clearance of acidic isoferritins from the circulation. The serum concentration of basic ferritin, however, can be useful in the diagnosis and management of some malignancies, and it is possible that studies on cell isoferritins can be important in biologic monitoring of neoplastic disorders. It should also be noted that the increased levels of serum ferritin found in patients with malignancy can exert adverse effects on the host immune response and perhaps an inhibitory effect on hematopoiesis.
Antibodies, Monoclonal↗
Peptichemio, vincristine, prednisone induction treatment in multiple myeloma.
Twenty-nine patients with multiple myeloma, 16 untreated and 13 relapsing after treatment with melphalan and/or cyclophosphamide, were treated with Peptichemio (PTC), vincristine (VCR) and prednisone (PRD). The treatment was well tolerated and produced rapid resolution of bone pain and improved performance status in symptomatic patients. Rapid and marked monoclonal component reduction (greater than 50 per cent) was noted in 50% of previously untreated and 31% of previously treated patients. The median survival of previously untreated patients was 27 months, 19 months for stage III patients. Four patients resistant to common alkylating agents responded to PTC-VCR-PRD treatment and achieved long remissions (from 18 to 38 months). The therapeutic results suggest that the present combination regimen may be indicated for induction treatment of multiple myeloma patients in an advanced stage of the disease, and for treatment of myeloma patients refractory or resistant to melphalan and/or cyclophosphamide.
Adult↗
Reevaluation of prognostic significance of symptoms in Hodgkin's disease.
The prognostic value--at diagnosis--of fever, sweating and weight loss, which enter the Ann Arbor B category, and of pruritus, whose influence on survival is still debated, were systematically reevaluated in 635 patients with Hodgkin's disease, observed between 1972 and 1982. By means of multivariate analysis an intrinsic, more negative prognostic value was demonstrated for each of the following symptoms: fever over 38 degrees C, weight loss more than 10% of body weight in the 6 months before admission, and severe pruritus, which is defined as being generalized, causing multiple excoriations and resisting local and systemic antipruritics. Patients with the mild counterparts of these symptoms, as well as sweats, were found to have a survival rate quite comparable with that of fully asymptomatic patients. A rearrangement of the Ann Arbor B constitutional symptoms which would replace sweats with severe pruritus might be more correct and more suitable for better selecting the patients who require more aggressive therapy.
Antineoplastic Combined Chemotherapy Protocols↗
LAV antibodies and IgG subclasses in haemophilia.
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Adolescent↗
[A case of scleroderma with sclerodermic renal crisis and association with the Vogt-Koyanagi-Harada syndrome].
We report a case of scleroderma with "scleroderma renal crisis", (arterial hypertension, high plasma renin levels and impaired renal function) associated with a Vogt-Koyanagi-Harada syndrome which includes neurological, ophthalmic and cutaneous symptoms. This case is interesting not only because both syndromes are rare and have not previously been reported in association, but because it suggests a pathogenetic relationship between two autoimmune diseases.
Acute Kidney Injury↗
Serum albumin in Hodgkin's disease.
Serum albumin levels were measured by electrophoresis in 552 evaluable patients with Hodgkin's disease. Determinations were made on all patients at onset, on 224 after induction therapy and on 78 in relapse after remissions of variable length. At onset a discrete hypoalbuminemia was evident, inversely related to stage and more marked in symptomatic cases and elder patients. Little or no differences in albumin levels were found with relation to histologic subtypes, sex and presence of weight loss or hepatic damage. Posttherapeutic normalization of serum albumin occurred only after achievement of complete remission and failed after partial remission, while a new clear decrease became evident in relapse. On the basis of 799 albumin measurements during active disease and in remission, the albumin/alpha 2-globulin ratio demonstrated a clear and useful clinical advantage over either albumin or alpha 2-globulin fractions alone as indicator of active disease and relapse. If defective synthesis is the most accepted mechanism for hypoalbuminemia in Hodgkin's disease, these results suggest a casual factor somehow related to the tumoral mass.
Adult↗
Prognostic factors in non-Hodgkin's lymphomas.
Prognostic factors were investigated in 67 patients with non-Hodgkin's lymphomas, homogeneously staged and treated (COP or CHOP according to low or high malignant histotype). A large number of parameters were scrutinized in order to recognize those exhibiting a prognostic value regarding length of survival. All the parameters that singly appeared to influence survival were entered into a multiple regression factor analysis. The erythrocyte sedimentation rate (ESR), higher or lower than 35 mm at the 1st h, better discriminated the groups of patients surviving or not at a given time. The histologic type, according to the Kiel classification of malignancy, was the second best prognosticator when a short-term prediction was requested (survival or death after no more than 2.5 years), but showed insufficient statistical weight for predicting longer survivals (greater than 4 years). Stage seemed to be the third best prognosticator for the first years of survival, but only the second best for longer survivals. Other parameters had very low prognostic importance when compared with those above. The results were substantially confirmed by 28 other patients, taken as controls. The importance that such a simple and easy test as ESR may be adequate with regard to prognosis is emphasized.
Adult↗
Blood glucose levels in Hodgkin's disease.
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Aged↗
Rate of M-component changes and plasma cell labeling index in 25 patients with multiple myeloma treated with peptichemio.
Twenty-five consecutive patients with previously untreated multiple myeloma were studied for bone marrow plasma cell labeling index, response to peptichemio induction therapy, and rate of M-component (MC) changes during the course of the disease. They received intermittent melphalan or cyclophosphamide as maintenance therapy and peptichemio associated with vincristine at first relapse. The response rate (76%) was independent of clinical stage, evaluated according to Merlini et al and to Durie and Salmon. Among responsive patients, rapid responders (half-life of MC decrease less than 47 days for IgA and IgG and less than 29 days for light chain myelomas) had a bone marrow plasma cell labeling index significantly higher (P less than 0.01) than that of slow responders. Rapid responders had a median survival of 15 months, while slow responders had a median survival of 42 months (P less than 0.05). The difference in survival between the two groups was accounted for mainly by the difference in duration of first response and the different rates of MC increase following it. Both of these parameters were directly related to the half-life of MC decrease at response in IgA and IgG myelomas. The duration of second response and the half-life of MC increase following it were shorter than the duration of first response and than the half-life of MC increase at first relapse.
Antineoplastic Combined Chemotherapy Protocols↗
The effect of ticlopidine on human endothelial cells in culture.
The effect of ticlopidine at various concentrations (150, 30, 6 microM), has been studied on cultured endothelial cells derived from human umbilical cord vein. Ticlopidine affects the initial attachment of endothelial cells to artificial substrata and has an inhibitory effect on endothelial cell growth rate which correlates to the concentration of the chemical in the culture medium. These effects are related to a marked reduction of intra- and extracellular fibronectin as evidentiated by immunofluorescence. The drug seems to interfere with the formation of fibronectin filaments from intracellular granules. The reduction of fibronectin availability could affect platelet adhesion to subendothelium as well as endothelial cell repair, and subsequently influence the bleeding time. The inhibition of cell proliferation and its possible effect on the thickness of the vessel wall should be considered as additional mechanisms of action for this substance.
Anticoagulants↗
Plasma cell DNA content in multiple myeloma and related paraproteinemic disorders. Relationship with clinical and cytokinetic features.
In 62 patients with multiple myeloma (MM) and related disorders, the nuclear DNA content distribution of bone marrow plasma cells was assessed by flow and conventional cytofluorometry. Abnormal distributions, suggesting the presence of aneuploid populations, were observed in 53% of MM at diagnosis, in 50% of benign monoclonal gammopathies and in 12% of Waldenström's macroglobulinemias. Eighty-six percent of aneuploid cases had DNA stem-lines falling between the diploid and triploid value. In advanced and relapsing MM, abnormal distributions were found in 75% of cases. In 4 out of 14 patients with MM serially studied during the course of disease, emergence of new abnormal clones was documented. The abnormal DNA content of bone marrow plasma cells was not correlated with any clinical and laboratory characteristic and it affected neither response to therapy nor survival in patients studied at diagnosis. In advanced phases of MM, the presence of abnormal clones was correlated with high plasma cell proliferation rates (studied by tritiated thymidine incorporation) and poor response to chemotherapy. Seven out of 8 patients in acute terminal phase of MM had abnormal clones. Among these, five had DNA stem-lines over triploid value.
Adult↗
Diabetes insipidus in the preleukaemic phase of acute non-lymphocytic leukaemia. A monosomy 7-associated condition?
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Acute Disease↗
Interactions between tumor cells and vascular endothelium.-I) Adhesion properties of cell lines with different metastasizing capacity.
The authors describe the adhesive properties of four murine tumor lines, chemically and virus induced, with different metastasizing potential. Cancer cells show similar behaviour in attachment kinetics when tested with endothelium monolayer or plastic surfaces, without differences between the lines with high or low malignancy. The time required for a complete adhesion to endothelial cells is three hours while to plastic surfaces is 90 min. The role of divalent cations is not required in the first phases of cellular attachment of tumor lines to plastic dishes.
Animals↗
Interactions between tumor cells and vascular endothelium.-II) Light and electron microscopic studies.
Electron microscope technique was used to investigate the passage across the endothelial monolayer by murine tumor lines. After the initial adhesion, cancer cells induce a retraction of endothelium and migrate under vascular intima. Subsequently they spread on basement membrane showing a flattened shape, meanwhile endothelial cells reconstitute the monolayer. The four tumor lines show a similar behaviour being able to induce endothelial retraction and exposure of extracellular matrix and cross through the monolayer. The technique appears useful to study in details this multi-step process.
Animals↗