Biomedical subjects
Publications and source records attributed to A Girolami.
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Sixteen patients with chronic idiopathic thrombocytopenic purpura underwent splenectomy after failure of steroid therapy. The average time of follow-up was 69 months. Immediately after splenectomy, complete response (platelets above 150 x 10(9)/l) was obtained by 68% of patients while 25% had partial response (platelets from 50 to 150 x 10(9)/l) and only in 1 patient splenectomy failed. During the long-term follow-up, 2 patients relapsed 9 and 20 years, respectively, after splenectomy (20% of non-responders). Partial recurrence of thrombocytopenia (partial response) was observed in 33% of the patients. The persistent complete response rate was then 47%. The young patient age appears to be the only positive predictive factor both for short-term and long-term response to splenectomy. The platelet recovery rate and postsplenectomy thrombocytosis are also early features of lasting response. Positive serum and platelet-associated immunoglobulins became negative after splenectomy, but there is no correlation with clinical response.
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Platelet-derived growth factor (PDGF) is thought to take part in the genesis of bone marrow fibrosis that can be found in patients with myeloproliferative diseases. We evaluated platelet mitogenic activity as the difference between serum and plasma activity in 8 patients with myeloproliferative disease. We observed a trend of lower values in 2 cases of polycythemia vera and 2 cases of essential thrombocythemia, as seen by other authors. Two patients suffering from chronic myeloid leukemia were within the normal range. In contrast, our 2 cases of idiopathic myelofibrosis showed increased levels. If confirmed by further studies, this could suggest a pathogenetic relationship between increased levels of PDGF and bone marrow fibrosis, and give differential diagnostic significance to the PDGF mitogenic assay in myeloproliferative diseases.
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Factor X Friuli was isolated from plasma by immunoaffinity and ion exchange chromatography and compared with normal factor X purified by the same method. Similar molecular weights were observed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of the intact or activated factor X molecules including their respective heavy and light chains. These data indicated that there were no gross structural differences between the normal and variant proteins. Immunochemical assays employing either polyclonal or 46 monoclonal antibodies (MoAbs) did not reveal any structural deviations. Two-dimensional peptide maps indicated that while the light chains of normal and Friuli factor X were very similar, the heavy chains of the native and activated molecules contained a limited number of differences. These data suggested that the defect in factor X Friuli may be a point mutation which lies within the activated heavy chain defined by the 195-424 amino acid sequence. Activation of factor X Friuli in purified systems showed that Russell's viper venom cleaved the molecule at 70% of the normal rate, while the rate of proteolysis of the variant protein was reduced 98% and 75% when incubated with the extrinsic and intrinsic activation complexes, respectively. These data support the clinical laboratory findings and the hypothesis that the defect associated with the Friuli variant may reflect an abnormal interaction between factor X Friuli and the nonproteolytic cofactors of the extrinsic and intrinsic factor X activation complexes. Fluorescence polarization studies suggested that a bound dansylated inhibitor of factor Xa was not oriented to the same extent within the active site of the variant enzyme relative to normal factor Xa until the addition of phospholipid and factor Va. Activated factor X Friuli generated thrombin from prothrombin in a purified system, but at one third the normal rate that was attributed to the Kcat suggesting a secondary effect of this defect.
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We developed assays for the measurement of Factor VIII in a Laser Nephelometer and the results were compared with those obtained by conventional immunological methods. Marked discrepancies were obtained using different antisera and only the Dako antiserum lot 42 B yielded satisfactory results. Other antisera used (other lots of Dako antiserum, Behringwerke antiserum and Immunoscientific antiserum) failed to yield satisfactory results. From our data it seems that Laser Nephelometer has no role in the evaluation of Factor VIII complex. Statements to the contrary have to be accepted with great caution.
The presence of gene lesions in coagulation factor X (FX, Stuart factor) was investigated in patients with FX deficiency or an FX abnormality (FX Friuli). The proposita had a heterozygous partial deletion of the FX gene with severe deficiency of FX activity and antigen. The lesion, which was inherited from her mother, removes the 3' portion of the gene coding for the catalytic domain of the factor. In this family, two differently affected FX genes are present, leading to double heterozygosity of the proposita and thus excluding consanguinity of parents. An apparently normal gene structure was observed in the other patient with FX abnormality, suggesting the presence of a small gene lesion.
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An additional TaqI restriction site was mapped in intron 2 of the factor XII gene. The site was found only in subjects with total or partial factor XII deficiency and thus represents the true gene lesion or a very tightly linked restriction fragment length polymorphism. The altered gene identified by this marker is present in four (three heterozygotes and one homozygote) of five unrelated Hageman trait subjects from different Italian regions. In the homozygous state the altered gene gives rise to a very marked reduction of factor XII activity. No deletion was found in the deficient factor XII genes.
Ascitic fluid reinfusion in severe cirrhosis has frequently been associated with intravascular coagulation (DIC). A low-grade DIC has been postulated to be present in liver cirrhosis. PT, APTT, fibrinogen, plasminogen, antiplasmin, fibrin degradation producers (FDP), euglobulin lysis time, tissue plasminogen activator, and fibrinopeptide A were investigated both in the plasma and ascitic fluid of cirrhotic patients before and after the concentration-reinfusion technique. Our results indicate that increased thrombin formation associated with hyperfibrinolysis is present in the plasma of cirrhotic patients. In ascitic fluid very high levels of thrombin and fibrinolysis activation were found. We conclude that (1) a DIC-like picture exists in ascites and (2) after ascites reinfusion procedures, ascitic fluid is the principal factor in the pathogenesis of DIC. During ascitic fluid reinfusion heparin treatment could be used successfully.
The aim of this study was to assess the cardiovascular and hormonal responses to 1-desamino-8,D-arginine vasopressin (DDAVP) in hypertensive patients before and after non-selective beta-blockade. We infused DDAVP at 400 ng/kg body weight for 10 min in nine subjects with mild essential hypertension before and 14 days after administration of nadolol at 80 mg/day. Blood pressure and heart rate were recorded, and blood was drawn at 0, 30 and 60 min for measurement of plasma renin activity, aldosterone, cortisol, noradrenaline, adrenaline and dopamine. Before the administration of nadolol, DDAVP induced a significant decrease in blood pressure, and significant increases in the heart rate, plasma renin activity, cortisol and noradrenaline; there were no changes in adrenaline or dopamine. After the administration of nadolol, baseline noradrenaline was significantly increased, while cortisol, adrenaline and dopamine remained unchanged. A second infusion of DDAVP did not significantly alter blood pressure, [corrected] heart rate, noradrenaline, adrenaline or dopamine, but plasma renin activity, aldosterone and cortisol still showed a significant increase. The blunted hypotensive effect of DDAVP after the administration of nadolol may be aspecific, due to lower basal blood pressure levels, or may indicate a mechanism of action common to both drugs. A similar post-DDAVP increase before and after beta-blockade suggests that the drug has a direct effect on the renin-secretory apparatus. An indirect effect, mediated by changes in intrarenal haemodynamics or by other factors with renin-stimulating activity, e.g. tissue plasminogen activator, can also be hypothesized.
Factor VIII/von Willebrand factor (VIII/vWf) related properties were studied in 10 patients affected by acute lymphoblastic leukemia during L-asparaginase-vincristine-prednisone treatment. These properties remained within the normal range during the period of observation without any difference from the basal values. On the contrary, VIII:C activity was already increased before medication and showed gradual additional elevation during the observation period, reaching a peak 1 week after discontinuation of L-asparaginase administration. Crossed immunoelectrophoresis of vWf, performed weekly in 2 patients during the period of medication, demonstrated a normal pattern before the beginning of treatment, but an apparently faster migrating peak during L-asparaginase therapy, suggesting a qualitative abnormality of vWf. No abnormal bleeding tendency was found in any of the patients.