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F Rodeghiero

Publications and source records attributed to F Rodeghiero.

At least 55 records · Page 3Linked to original sources
PubMed2000

The A20210 allele in the prothrombin gene enhances the risk of venous thrombosis in carriers of inherited protein S deficiency.

Sixteen families with inherited protein S deficiency and venous thromboembolism (VT) were screened for the presence of factor V (FV) Leiden mutation and for the G20210A allele in the prothrombin gene. While FV Leiden was not detected in any of the families, protein S deficiency and prothrombin mutation were present in five families. To assess the risk of VT in carriers of the combined defects, a total of 92 members of the 16 families, including propositi, were examined. Thirty subjects were normal, 40 showed protein S deficiency, 10 the prothrombin mutation and 12 showed both abnormalities. When index cases were excluded, thrombosis history were present in 40.7% of protein S-deficient patients, 75% of patients with combined abnormality, one out of the 10 (10%) with prothrombin mutation and only one (3.3%) of the normal subjects. Relatives with combined defects showed the highest incidence rate of VT in comparison with normal relatives (rate ratio = 32.4), those with protein S deficiency an intermediate degree (rate ratio = 15.7), and G20210A relatives the lowest (rate ratio = 3.4). Relatives with combined defects had an increased risk of VT in comparison with relatives with protein S deficiency (incidence rate ratio 2.1; 95% confidence interval, 0.7-5.41; P = 0.1). In conclusion, the presence of the prothrombin mutation seems to increase the risk of VT carriers of protein S deficiency, although additional families are required to fully estimate the magnitude of risk.

Adult↗
PubMed2000

Von Willebrand Disease type 2M "Vicenza" in Italian and German patients: identification of the first candidate mutation (G3864A; R1205H) in 8 families.

Von Willebrand disease type 2M "Vicenza" (VWD 2M V) is characterised by autosomal dominant inheritance, low von Willebrand factor (VWF) and the presence of "supranormal" multimers in plasma. This specific phenotype has been described in Italian and recently also in German patients. The molecular defect is linked to the VWF gene. However, no specific mutations have been identified until now. We analysed the complete coding region and adjacent intron sequences of the VWF gene in Italian families in comparison to German families with VWD 2M V by a PCR-based mutation screening, combined with SSC- and heteroduplex-analysis of exons 2 through 52, followed by direct sequencing. We identified the first heterozygous candidate mutation (G3864A; R1205H) in all affected members of the 7 Italian families and in 1 German patient but not in the unaffected family members nor on 100 chromosomes of normal subjects, suggesting a causal relationship between the mutation and the phenotype. Haplotype identity, with minor deviations in one Italian family, suggests a common but not very recent genetic origin of R1205H.

Female↗
PubMed2000

A comparative evaluation of gene transfer into blood cells using the same retroviral backbone for independent expression of the EGFP and deltaLNGFR marker genes.

BACKGROUND AND OBJECTIVES: Retroviral vectors are widely used to deliver foreign genes to hematopoietic stem cells (HSC). Improvement of marking protocols needs reporter genes to allow rapid detection and efficient selection of transduced cells. The great potential of EGFP and LNGFR as reporter systems prompted us to compare them simultaneously, using the same retroviral backbone and the same gene transfer procedures. DESIGN AND METHODS: The EGFP and LNGFR coding sequences were separately cloned into the MFG retroviral backbone. A cloning strategy assuring that both genes utilize the same ATG as the start codon was adopted. Marker gene expression, viral titers, transduction efficiency, and vector stability were evaluated in expanded amphotropic packaging clones and human hematopoietic cell lines by flow cytometry and PCR analysis. Vectors were also tested for their ability to transduce CD34+ peripheral blood cells. RESULTS: A significantly larger number of MFG- LNGFR packaging clones were obtained that produced high viral titers. A direct correlation between viral titer and marker gene expression in packaging clones was demonstrated for both constructs. Similar expression kinetics and absence of in vitro toxicity in transduced cells were also observed for both constructs. Successful infection of CD34+ cells was achieved even after a short time of exposure to recombinant viruses. INTERPRETATION AND CONCLUSIONS: Our results demonstrate that EGFP and LNGFR marker genes are equally useful for a rapid, specific and non-toxic detection of transduced cells. The MFG-EGFP construct appears useful to optimize gene transfer protocols in vitro. On the other hand, the MFG-LNGFR construct, for making possible a more efficient selection of high titer producer clones, as well as for safety and adaptability to the in vivo use, is more suitable for clinical applications.

Cell Line↗
PubMed2000

Acquired von Willebrand syndrome: data from an international registry.

The acquired von Willebrand syndrome (AvWS) is a rare bleeding disorder with laboratory findings similar to those of congenital von Willebrand disease (vWD). Despite the numerous cases reported in the literature until 1999 (n = 266), large studies on AvWS are not available. Moreover, diagnosis of AvWS has been difficult and treatment empirical. These considerations prompted us to organize an international registry. A questionnaire, devised to collect specific information on AvWS, was sent to all the members of the International Society on Thrombosis and Haemostasis (ISTH), who were invited to respond if they had diagnosed cases with the AvWS cases. 156 members answered the questionnaire and 54 of them sent information on 211 AvWS cases from 50 centers. Data were compared with those already published in the literature and 25 cases already described or not correctly diagnosed were excluded. The 186 AvWS cases that qualified for the registry were associated with lymphoproliferative (48%) and myeloproliferative disorders (15%), neoplasia (5%), immunological (2%), cardiovascular (21%) and miscellaneous disorders (9%). Ristocetin cofactor activity (vWF:RCo) or collagen binding activity (vWF:CBA) were usually low in AvWS (median values 20 U/dL, range 3-150), while factor VIII coagulant activity was sometimes normal (median 25 U/dL, range 3-191). FVIII/vWF inhibiting activities were present in only a minority of cases (16%). Bleeding episodes in AvWS were mostly of mucocutaneous type (68%) and were managed by DDAVP (32%), FVIII/vWF concentrates (37%), intravenous immunoglobulins (33%), plasmapheresis (19%), corticosteroids (19%) and immunosuppressive or chemotherapic agents (35%). Based upon the data of this international registry, it appears that AvWS is especially frequent in lympho- or myeloproliferative and cardiovascular diseases. Therefore, AvWS should be suspected and searched with the appropriate laboratory tests especially when excessive bleeding occurs in patients with these disorders. On the basis of the information provided by this registry guidelines for diagnosis and management of the AvWS are given.

Adolescent↗
PubMed2000

The VITA Project: heritability of resistance to activated protein C. Vincenza Thrombophilia and Arteriosclerosis.

Resistance to activated protein C (APC) is a risk factor for venous thromboembolism also in absence of the FV Leiden mutation. To evaluate the influence of genetic factors on APC resistance, we evaluated the heritability of the APC resistance phenotype in 1,519 sib-parent pairs randomly selected from the VITA Project. After adjustment for known influencing factors, a high heritability coefficient (0.58) was observed and parental response to APC was the single most important factor in predicting the corresponding phenotype in sibs. In 32 parent-sib pairs in which phenotypic resistance to APC unrelated to FV Leiden was present in both parents and sibs, no additional mutation on the 306-aminoacid residue of FV (FV Cambridge and FV Hong Kong) was found. In these 32 parent-sib pairs, FVIII:C and vWf:Ag levels were not significantly increased and there was no excess prevalence of the R2 allele of exon 13 of FV gene. This study suggests that the response to APC is significantly influenced by genetic factors also at a population level, but the responsible mechanisms are still undefined.

Activated Protein C Resistance↗
PubMed1999

Activated protein C resistance and factor V Leiden mutation are independent risk factors for venous thromboembolism.

BACKGROUND: Resistance to activated protein C due to the factor V R506Q (Leiden) mutation is the most common clotting abnormality in patients with venous thromboembolism. OBJECTIVE: To evaluate the risk for venous thromboembolism associated with the factor V Leiden mutation or with resistance to activated protein C in the general population. DESIGN: Cross-sectional survey. SETTING: General community of Vicenza, Italy. PATIENTS: A population-based sample of 15,109 white persons 18 to 65 years of age who were randomly selected from the census list. MEASUREMENTS: Sequential validated approach based on participants' reports and Doppler ultrasonography. Resistance to activated protein C was investigated in all participants; 2134 participants with resistance to activated protein C were screened for the factor V Leiden mutation. RESULTS: Carriers of the factor V Leiden mutation had a relative risk of 3.3 (95% CI, 1.7 to 6.1) for venous thromboembolism before 65 years of age. The fraction of cases attributable to the factor V Leiden mutation was 6.6%. By 65 years of age, 5.7% of carriers of the mutation had had venous thromboembolism, mostly after surgery. Participants with a reduced response to activated protein C were at higher risk even if they did not carry the mutation (odds ratio, 1.7 [CI, 1.0 to 2.7]); the attributable risk for venous thromboembolism was 5.1%. CONCLUSIONS: The factor V Leiden mutation and resistance to activated protein C are important, independent risk factors for venous thromboembolism. Screening strategies for the factor V Leiden mutation in patients undergoing surgery or experiencing major trauma cannot be recommended, but phenotypic evaluation of resistance to activated protein C should be encouraged in patients with venous thromboembolism.

Activated Protein C Resistance↗
PubMed1999

Pseudohomozygosity for activated protein C resistance is a risk factor for venous thrombosis.

Pseudohomozygosity for activated protein C resistance (APC-r) is a rare condition due to the association of heterozygous FV Leiden mutation and partial type I FV deficiency. To assess the risk of venous thromboembolism in these subjects, seven families including 11 pseudohomozygotes and 45 relatives were examined. Among the relatives, 16 were heterozygous FV Leiden carriers, nine showed partial FV deficiency and 20 no abnormalities. Deep vein thrombosis occurred in 4/11 (36.3%) pseudohomozygous patients versus 6/16 (37. 4%) FV Leiden carriers and 1/20 (5%) normal relatives. Pseudohomozygotes and FV Leiden carriers had a significantly increased risk of venous thrombosis in comparison to normal relatives (RR 8.8 and 5.7, respectively). There was no difference between the thrombotic risk of pseudohomozygous subjects and of FV Leiden carriers (RR 1.6, 95% CI 0.43-5.7). Furthermore, there was no difference in thrombosis-free survival between pseudohomozygotes and 45 consecutive FV Leiden heterozygous outpatients, suggesting that a referral bias may explain the apparent younger age of thrombosis in the pseudohomozygotes in comparison to relatives with FV Leiden heterozygosity (27 years v 54 years; P = 0.01). Pseudohomozygosity for APC resistance carries a significantly higher risk for venous thromboembolism in comparison to normal subjects, but probably not in comparison to heterozygous FV Leiden carriers.

Activated Protein C Resistance↗
PubMed1999

Detection of identical T-cell clonotype expansions in both the donor and recipient after allogeneic bone marrow transplantation.

Using phenotypic, functional and molecular techniques, this study was performed to compare the complexity of the T-cell receptor repertoire of a bone marrow transplanted patient with that of his HLA-matched related donor, both of whom developed a chronic lymphocytosis sustained by CD3+CD8+CD57+CD16-CD56- granular lymphocytes 3 years after transplantation. Although Southern blot analysis revealed the presence of extra bands in both subjects, thus indicating the presence of at least one clonal T-cell population, the study of the different T-cell receptor Vbeta (TCRBV) usage did not demonstrate discrete overexpression of any TCRBV segments. On the contrary, heteroduplex analysis of TCRBV transcripts suggested the presence of oligoclonal T-cell expansions in the two subjects. Cloning and sequencing studies demonstrated that T-cell clones expressing identical TCRBV chains were expanded both in the donor and in the recipient. Furthermore, clones with similar, but not identical, junctional regions were also found in the two subjects. These data indicate that, at the time of the graft, a few cells with a monoclonal/oligoclonal pattern that were present in the donor were transferred to the recipient, where they may have found the same environmental in vivo conditions and/or the antigenic pressure favouring their abnormal expansion.

Adult↗
PubMed1999

Rabbit antithymocyte globulin (r-ATG) plus cyclosporine and granulocyte colony stimulating factor is an effective treatment for aplastic anaemia patients unresponsive to a first course of intensive immunosuppressive therapy. Gruppo Italiano Trapianto di Midollo Osseo (GITMO)

About 30% of patients with severe aplastic anaemia (SAA) unresponsive to one course of immunosuppressive (IS) therapy with antithymocyte or antilymphocyte globulin can achieve complete or partial remission after a second IS treatment. Among various second-line treatments, rabbit ATG (r-ATG) could represent a safe and effective alternative to horse ALG (h-ALG). In a multicentre study, 30 patients with SAA (17 males and 13 females, median age 21 years, range 2-67) not responding to a first course with h-ALG plus cyclosporin (CyA) and granulocyte colony stimulating factor (G-CSF), were given a second course using r-ATG (3.5 mg/kg/d for 5 d), CyA (5 mg/kg orally from day 1 to 180) and G-CSF (5 microg/kg subcutaneously from day 1 to 90). The median interval between first and second treatment was 151 d (range 58-361 d). No relevant side-effects were observed, but one patient died early during treatment because of sepsis. Overall response, defined as transfusion independence, was achieved in 23/30 (77%) patients after a median time of 95 d (range 14-377). Nine patients (30%) achieved complete remission (neutrophils >/=2.0 x 109/l, haemoglobin >/=11 g/dl and platelets >/=100 x 109/l). The overall survival rate was 93% with a median follow-up of 914 d (range 121-2278). So far, no patient has relapsed. Female gender was significantly associated with a poorer likelihood to respond (P = 0.0006). These data suggest that r-ATG is a safe and effective alternative to h-ALG for SAA patients unresponsive to first-line IS treatment.

Adolescent↗
PubMed1999

Homocysteine levels in polycythaemia vera and essential thrombocythaemia.

Patients with polycythaemia vera (PV) or essential thrombocythaemia (ET) have an increased risk of arterial and venous thromboembolic complications. Since hyperhomocysteinaemia (HHC) is a risk factor for vascular disease, we investigated the frequency of HHC in these disorders and analysed a possible association of elevated plasma homocysteine levels with vascular complications. In the cohort of 134 patients from Vienna (69 female, 65 male, median age 65.5 years, range 21-91 years) with PV (n = 74) or ET (n = 60), plasma homocysteine levels were significantly higher compared to 134 healthy controls. Median homocysteine level was 12.3 micromol/l (range 3.5-48.4 micromol/l) in patients with PV or ET and 8.9 micromol/l (range 4.8-30.5 micromol/l) in normal controls (P < 0. 0001). In addition to the 134 patients from Vienna, 48 patients (28 female, 20 male; median age 66.5 years, range 24-82) from Vicenza with PV (n = 25) or ET (n = 23) were included to evaluate the impact of HHC on the risk of thrombosis. Of 59 patients with HHC (44 from Vienna and 15 from Vicenza) 18 (31%) had a history of arterial and 10 (17%) of venous thrombosis. Of 123 patients with normal homocysteine levels, 30 (24%) had arterial and 16 (13%) had venous thromboses. The difference between the two groups was statistically not significant. Even though mild to moderate HHC occurred in a larger number of patients with PV or ET and thrombosis, it can presently not be regarded as an additional risk factor for thrombosis.

Adult↗
PubMed1999

Inconsistency of association between type 1 von Willebrand disease phenotype and genotype in families identified in an epidemiological investigation.

In a previous epidemiological investigation among schoolchildren of Northern Italy, a conservative 1% prevalence of type 1 von Willebrand disease (VWD) was found. Diagnosis was based on a positive family history and low von Willebrand factor (VWF) ristocetin cofactor activity. To investigate whether the type 1 VWD phenotype as detected by our original methodology cosegregates with one or more specific alleles of the VWF gene, we have performed genotype analysis in affected subjects and their family members. Eleven of the 14 subjects previously identified as having VWD, all with mild personal bleeding symptoms, agreed to participate in the genetic study. Remarkably, the laboratory measurements of the previous investigation were completely confirmed in 10 of the 11 subjects. Clear cosegregation of the VWD type 1 and a specific VWF allele was observed in one family and was likely in the family of two other pro-bands. In three additional propositi and their families a possible association of the phenotype with a VWF allele was found. No association was observed in the remaining five subjects and their families. During 13-year follow-up few additional bleeding episodes were recorded among investigated subjects, most often occurring in the one family manifesting clear cosegregation. The results of this study illustrate that a personal and family bleeding history and persistently low VWF ristocetin cofactor activity, fitting the usual criteria for type 1 VWD, may not cosegregate with genetic markers at the VWF gene locus. Thus the prevalence of VWD defined as a disorder involving the VWF locus might be overestimated in population study. However, phenotypic diagnosis still remains fundamental to identify patients at risk of bleeding. Further research should clarify whether in families with more severe clinical and laboratory phenotype a clear association with markers of VWF is found.

Alleles↗