Biomedical subjects
Publications and source records attributed to M G Mazzucconi.
A family with factor XII severe congenital deficiency is described. Factor XII activity and factor XII antigen were both undetectable in the propositus plasma; levels of FXII:C and FXII:Ag were intermediate in heterozygotes. Plasma prekallikrein activity was low in the propositus, whereas normal levels of antigen could be found, suggesting a defect of kallikrein activation due to factor XII deficiency.
We have followed up 63 pregnancies in women with autoimmune thrombocytopenic purpura (ATP). Of these, 15 were previously splenectomized. The characteristics of the sample can be summed up as follows: average age 27 years (17-41); platelets at the beginning of pregnancy, mean 129.5 x 10(9)/l (range 16-488); platelets at delivery, mean 133 x 10(9)/l (range 8-477); PA-IgG at delivery, mean 320 ng IgG/10(7) platelets (range 10-1000); SPB-IgG at delivery, mean 262 ng IgG/10(7) platelets (range 10-1000). There were 30 spontaneous deliveries and 33 cesarean sections. Forty-two newborns had a platelet count within the normal range while nine had a platelet count less than or equal to 150 x 10(9)/l, while six had less than or equal to 100 x 10(9)/l and a further six less than or equal to 50 x 10(9)/l. The aim of this study is the evaluation of maternal risk and of possible feto-neonatal thrombocytopenia at birth. In this regard, the following parameters were considered: previous maternal splenectomy; the platelet count at the beginning of pregnancy; the platelet count and the titres of PA-IgG and SPB-IgG at delivery. Preliminary statistical evaluation of these parameters enabled us to identify a risk score. From this it was possible to obtain an optimum management of the final stage of pregnancy regarding the therapeutic approach and the timing of delivery.
Abnormal fibrinolysis and thrombotic complications have been often observed in patients who had undergone surgery for meningioma. Fourteen patients, affected by meningioma, were studied before surgery, during surgery and 24 h after surgery in order to evaluate the modifications of the fibrinolysis system and the coagulation physiological inhibitors. Before surgery, no patient showed hyperfibrinolysis and/or modifications of coagulation physiological inhibitors. During surgery, an activation of fibrinolysis with pathological levels of tissue plasminogen activator activity (mean = 6.33 U/dl, SD = 7.9, p = 0.02) and increased levels of fibrin degradation products (mean = 0.21, SD = 0.18, p = 0.002) was noted. Modifications of the fibrinolysis parameters occurred only in 9/14 patients (64%). These patients presented a more vascularized tumour, revealed before surgery by computerized tomography scan and cerebral arteriography and directly confirmed during the resection. Twenty-four hours after surgery no patient presented fibrinolysis activation. There was no evidence of disseminated intravascular coagulation in our patients. None of them presented pathological decrease of the physiological coagulation inhibitors or thrombotic complications. In conclusion, during surgery, fibrinolysis parameters show important modifications in patients with vascularized meningioma suggesting an ongoing tumour-host interaction. These variations must be taken in account, in order to plan timely a correct therapeutic approach.
BACKGROUND: Anagrelide, an imidazo-quinazolin compound first proposed as a potent inhibitor of platelet function, was subsequently recognized as a drug able to lower the platelet number both in normal subjects and in myeloproliferative syndromes with thrombocytosis. We report our experience with Anagrelide therapy in 20 patients affected by essential thrombocythemia (E.T.). PATIENTS AND METHODS: Twenty consecutive patients with E.T. entered the study from June, 89 to July, 91. Therapy schedule was as follows: 0.5 mg every 12 hours for 7 days; subsequently the daily dose was increased by 0.5 mg/day every week until a response was obtained (a decrease of the platelet count to less than 500 x 10(9)/l = complete response; to less than 600 x 10(9)/l = partial response). RESULTS: Of 19 evaluable patients, complete response (CR) was obtained in 13 (68%) and partial response (PR) in 3 (16%). For all responders, the mean time to response was 5.2 months: mean daily dose of Anagrelide 2 mg. Side effects were recorded in 8/20 patients (40%): tachycardia (n = 4), gastrointestinal distress (n = 3), perimalleolar edema (n = 1). In 6 cases therapy was discontinued definitively. DISCUSSION: Response rate to therapy with Anagrelide is similar to that with alkylating agents and alpha 2b-recombinant interferon; furthermore, Anagrelide is a drug without cytotoxic properties. The mean daily dose able to obtain a response is 2 mg, but maintenance therapy at similar doses is always necessary. In conclusion, we can say that Anagrelide is an effective drug in the treatment of patients with E.T., but its side effects must be seriously considered. A larger study may show whether it should be considered as a "first-line" drug for all patients with E.T.
We report the results of a randomized clinical trial of two different coricosteroids (prednisone versus deflazacort) in patients affected by autoimmune thrombocytopenic purpura (ATP). We have evaluated the efficacy of the two steroids on platelet count, antiplatelet antibodies, lymphocyte subsets and the occurrence of side effects. Twenty-seven patients were evaluable: 13 were treated with PDN and 14 with DFC. After 24 weeks of treatment, 4/12 (33%), subjects treated with PDN were refractory while complete responses were obtained in 2/12 (17%) and partial responses in 6/12 (50%). Among patients treated with DFC, 4/11 (36%) were considered as refractory, 2/11 (18%) had a complete response and 5/11 (46%) a partial response. A statistically significant decrease of antiplatelet antibodies was recorded in both groups after 4 weeks of therapy, but only in subjects receiving PDN did the reduction last until the 24th week. We observed an increase of T lymphocyte subsets (CD3, CD2, CD4, CD8) in absolute number, due to an increase in circulating lymphocytes, after 4 weeks. No substantial modifications were observed in these populations regarding the percentage or the CD4/CD8 ratio. After 24 weeks, 91% (10/11) of patients treated with PDN presented an increase of body weight and 1 had a stable increase in blood pressure. Among the subjects treated with DFC, 64% (7/11) showed an increase of body weight after the same follow-up. In conclusion, no difference was observed the two steroids studied.
Sixty probable carriers of haemophilia from 25 families were studied by using coagulation phenotype and DNA analysis: 33 with haemophilia A and 27 with haemophilia B. Coagulation phenotype was based on factor VIII/IX assay and DNA analysis on the examination of restriction fragment length polymorphisms (RFLPs) within and closely linked to factor VIII or IX: 3 RFLP for factor VIII and 3 for factor IX. The comparison between the coagulation phenotype and RFLP analysis showed the misclassification of 15 females (6 for haemophilia A and 9 for haemophilia B). Four prenatal haemophilia A diagnosis were made by DNA analysis of chorionic villi, taken with a transcervical trophoblastic biopsy, between the 18th and the 11th week.
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We report a study concerning 100 patients affected by essential thrombocythemia: 90 adult (age greater than 20 years) and 10 pediatric subjects. The diagnosis was made by chance (78%), because of hemorrhages (10%), thrombosis (9%), vasomotor symptoms (29%). In the adult group, single-agent chemotherapy was performed with good remission using pipobroman or interferon. Antiaggregant agents were used in all patients at diagnosis. During the clinical course only a few complications occurred.
We performed 56 HDIVG administrations in adults (26) and children (30) affected by idiopathic thrombocytopenic purpura with two different schedules: a five-day course at 400 mg/kg/d and a "bolus" 1 gr/kg. Forty-five cases were treated in preparation for surgical operations and eleven for bleeding episodes. Response to the five-day course in adults was good in 3/24, fair in 13/24, poor in 8/24, while in children it was good in 14/26, fair in 9/26, poor in 3/26. The difference between adults and children is statistically significant. None of the responder patients submitted to surgical operation needed platelet infusions during surgery. Response to the "bolus" schedule (6 cases) in adults was poor in 1 case and good in the other one, and in children, fair in 3 cases and good in the other one. In responder patients treated for bleeding episodes we obtained clinical improvement with hemorrhage arrest. In adults the treatment was well-tolerated, while in children we observed 3/30 mild side effects and 1/30 important side effect.
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This retrospective study, including 118 patients with acute lymphoblastic leukemia (ALL) aged greater than 15 years, with a minimum follow-up of 6 years, was aimed at defining potentially "cured" adults with ALL. At present, 21 out of 92 patients who achieved complete remission (CR) are long survivors: 16 in first CR, off-therapy; 4 in 2nd CR (3 off-therapy); 1 in 3rd CR, on treatment. On the basis of available data, we tried to identify factors at diagnosis which might predict long-term survival: white blood cell (WBC) count on admission was the only significant prognostic factor for overall survival (p = 0.0002) and first CR duration (p = 0.0005). The survival hazard rate (risk of death from acute leukemia per day) reaches 0 between 8 and 9 years from diagnosis. From our data we can identify two groups of ALL long-term survivors: the first includes 16 patients in 1st continuous CR (CCR), 12 of whom in CCR for over 8 years may be considered "cured"; the second group comprises 5 patients, relapsing once or twice, alive in 2nd or 3rd CR.
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Explore the source record for details and available documents.
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Hepatitis C is an important complication of therapy with coagulation factor concentrates; in fact, more than 90% of post transfusion hepatitis is caused by hepatitis C. Evaluation of HCV antibodies has been carried out mainly with the ELISA method but this test generates false positive results. Therefore, we studied ninety coagulopathic patients with the aim of determining the prevalence of hepatitis C virus (HCV) antibodies using the ELISA and RIBA methods. Our study confirms that the ELISA method presents false positivities: of 60 ELISA positive patients, only 41 were confirmed by RIBA. We found a significant correlation between HCV positivity, ALT titre and the number of concentrates used annually. In conclusion, our data suggest that the RIBA test is a useful confirmatory method in ELISA HCV-positive patients. This fact is particularly important in coagulopathic patients, in whom progression of chronic hepatitis C to cirrhosis is elevated.
We report the case of a young hemophilic patient with antibodies against the human immunodeficiency virus (HIV) who was affected by immune thrombocytopenic purpura (ITP). This condition did not respond to pharmacological therapy with steroids and alpha-2b-r-IFN, and the patient was splenectomized. Immune status evaluation was performed before and after surgery and during follow-up with CD4-CD8 monoclonal antibodies and cytofluorimetric analysis in order to explore possible correlations between splenectomy and the cytologic immune regulatory system. Splenectomy resulted in a resolution of ITP with consequent disappearance of the hemorrhagic diathesis related to thrombocytopenia. Moreover, at 30 months from splenectomy the patient is still in remission, his CD4 count is not decreased, and no progression to AIDS has been evidenced. These aspects are analyzed and briefly discussed.
We report the case of a young HIV seropositive patient with severe hemophilia A who presented rapid liver failure related to his chronic C hepatitis. The patient had been receiving factor VIII:C clotting factor concentrates (mean 60,000 U/year) since 1975. In 1984 alanine aminotransferase presented abnormal levels. The CD4 lymphocyte count in 1991 was normal and ultrasonographic scan showed normal liver morphology. In 1991 the patient were found to be seropositive for HCV antibodies as detected by the ELISA method and confirmed by the RIBA method. One year later, a progressive increase in policlonal gamma-globulin and a decrease in the CD4+ lymphocyte count to below 500/muL were detected in concomitance with ultrasonographic evidence of a progressive increase in the longitudinal diameters of the liver and spleen and signs of liver inhomogeneity. A significant inverse correlation was observed between the increase in the longitudinal diameter of the liver and the decline in albumin levels, and between the increase in the longitudinal diameter of the liver and the drop in platelet count. Elevated levels of ammonemia, gamma-glutamyl transpeptidase, alkaline phosphatase and IgA were detected. Moreover, decreased levels of the C4 and C3 complement fractions were documented. At this time (1994), esophagogram and esophagogastroscopy evidenced varicosities in the lower esophageal section (stage F1). The patient died in 1995 March at the age of 29 years of sudden septic shock related to Pseudomonas aeruginosa infection.