[The anti-factor Xa plasma activity in patients receiving coumarin derivatives therapy (author's transl)].
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Biomedical subjects
Publications and source records attributed to E Pogliani.
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Glomerulonephritis in idiopatic mixed cryoglobulinemia represents perhaps a glomerular damage by immune complexes. In this study, a sigmoidal-like curve was obtained after addition of 13 different mixed cryoglobulins to both autologous and isologous platelet-rich plasma, tested in platelet aggregometer. The lag phase of the curve corresponds to platelet phagocytosis of cryoglobulin-binding ferritin, as shown in electron microscopy and the optical density decrease phase corresponds to the aggregation of platelets that shows the same ultrastructural characteristics of ADP-induced platelet aggregation. This platelet aggregation is inhibited by different drugs. Intraglomerular platelet aggregation by cryoglobulins might play a key role in determining the glomerular damage in cryoglobulinemia by the release of nucleotides and vasoactive amines.
We describe a case of IgM paraproteinemia, whose macroblogulin reacted anomalously with heparin. Anti-heparin activity of the paraprotein was suggested by insensibility of the patient's plasma to heparin in heparin-thrombin clotting time. Moreover, the presence of heparin in the medium markedly reduced the inhibitory effect of the paraprotein on platelet aggregation by ADP.
102 sera from polytransfused patients have been screened in platelet aggregometry. Anti-human platelet isoantibodies, tested against 'responsive' human platelets in PRP, give in the aggregometer a decrease in optical density recorded as a sigmoidal curve. In the first step of reaction PF3 availability suggests that the primary action of antibody is to damage the platelet membrane. The second step might be a true aggregation (an ADP-mediated platelet clumping) or a platelet lysis, depending on the type and the potency of antibody, on the type of platelets (normal or thrombasthenic) and on some experimental conditions. These conclusions, confirmed by electron microscopy findings, suggest that aggregometry is a very rapid and simple method of detecting platelet antibodies.
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The inhibition of restriction enzyme digestion of lambda phage DNA by anthracyclines (i.e., adriamycin, daunomycin, epirubicin, idarubicin and esorubicin) commonly used in the treatment of human leukemia and cancer has been studied in vitro. The anthracyclines used inhibit DNA digestion by SmaI, AvaII, HaeIII, HhaI and HpaII, which cut DNA at guanine-cytosine (G-C) sequence sites, and by EcoRI, which cut DNA at adenine adenine-thymine thymine (AATT) sequence sites. Adriamycin completely inhibits DNA restriction by the indicated enzymes, daunomycin, epirubicin and idarubicin determine only a partial inhibition, while esorubicin does not inhibit DNA restriction at all. An attempt is made to correlate the extent of the in vitro interaction between anthracyclines and DNA to in vivo cardiotoxicity.
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Patients with chronic myeloproliferative disease are at increased risk of both thromboembolic and haemorrhagic complications. Cerebral thrombosis is a common cause of death in myeloproliferative disease patients. Picotamide is a new anti-platelet drug sharing a dual anti-thromboxane activity: inhibition of thromboxane A2 synthase and thromboxane A2 receptor antagonism. Picotamide inhibits in vitro and ex vivo platelet aggregation induced by different agonists. Interestingly, in vitro studies show that picotamide is able to increase prostacycline biosynthesis. In the clinical setting, picotamide treatment induces only a slight prolongation of bleeding time. The safety and efficacy of picotamide long-term treatment in 15 patients with essential thrombocytosis and a positive history of previous thromboembolic events was evaluated. After 12-month treatment with picotamide no patients suffered from thrombotic events and only one minor and transient bleeding episode was observed. This observational long-term trial shows that picotamide treatment in patients with thrombocytosis at high risk of thrombotic events is safe and well tolerated. Picotamide did not increase the risk of bleeding in these patients, while at the same time, no thrombotic events were observed during the 1-year treatment.
Tumor necrosis factor-alpha (TNF-alpha), a cytokine provided by both immunomodulating and inflammatory activities, has been described to be abnormally increased in the blood of patients affected by malignant lymphomas, particularly NHL. However, the biological and clinical significance of TNF-alpha secretion in malignant lymphomas is still controversial. The present study was carried out to further define TNF-alpha secretion in untreated malignant lymphomas and during low-dose IL-2 immunotherapy. The study included 80 malignant lymphoma patients, 54 of whom were affected by HD and the other 26 by NHL. The mean TNF-alpha serum concentrations observed in untreated lymphoma patients were significantly higher than those seen in the healthy controls, without significant differences between HD and NHL. Moreover, both HD and NHL lymphoma patients at clinical stage III-IV showed significantly higher mean TNF-alpha levels than those at clinical stage I-II. Finally, patients with systemic symptoms had higher mean TNF-alpha concentrations than those without any systemic symptoms, even though statistical significance was observed only for NHL patients. In a second study we have evaluated changes in TNF-alpha levels in seven evaluable lymphoma patients (NHL: 6; HD: 1)--who did not respond to conventional therapies--during subcutaneous low-dose IL-2 (3 MIU/day, 6 days/week for 4 weeks). Long-term stable disease was achieved in four patients with NHL, whereas the other three progressed. In patients with stable disease the mean TNF-alpha concentrations significantly decreased during treatment, whereas they increased in progressing patients. This study, by showing an abnormally enhanced TNF-alpha secretion in both NHL and HD patients with advanced disease and systemic symptoms and a decrease in its levels in patients who achieved disease control on IL-2 immunotherapy, appears to confirm the unfavorable prognostic significance of enhanced TNF-alpha levels in malignant lymphomas.