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Biomedical subjects

F Rodeghiero

Publications and source records attributed to F Rodeghiero.

At least 91 records · Page 5Linked to original sources
PubMed1997

[Prevention of hemorrhage and dental treatment of patients with congenital or acquired coagulopathies].

The physiopathology of the hemorrhagic blood coagulation disorders caused by genetic or aquired problems is described. Among the former the most frequent ones include the hemophilia of type A-B and the von Willebrand disease, among the latter the use of oral anticoagulant constitutes the most frequent cause. If the are not subjected to an adequate haemostatic prophylaxis, both patients with hemophilia and von Willebrand disease present a serious haemorrhagic risk as a consequence of dental practice. As far as the use of anticoagulants is concerned, a periodical monitoring of the time of prothrombin (PT) is needed to find the right dosage (TP between 20%-30% or INR--international normalized radio between 2 and 3.5). Values over this range cause an increase of the hemorrhagic risk, while lower values involve an increased risk of thrombotic events. According to the authors the patients with the hemorrhagic diathesis show a precise handicap, caused both by his illness and by environmental elements, such as the fear of doctors for the haemorrhagic complications consequent to a therapeutical operation, fear that often leads to neglect important medical measures, in particular dental measures. The specialized dental surgeon has to mantain a strict cooperation with the hematologist in order to arrange an appropriate procedure of the prophylaxis. As far as the hemostatic prophylaxis is concerned, the use of the dermopressin (DDAVP), in patients with hemophilia A and von Willebrand disease, guarantees the realisation of dental practice without hemorrhagic risk. On the contrary, the use of the tranhexanic acid on patients in an anticoagulant oral treatment gives hemostatic security and makes it possible to carry on the therapy and the out-patient treatment.

Blood Coagulation Disorders↗
PubMed1996

Validated questionnaire for the identification of previous personal or familial venous thromboembolism.

The recognition of previous episodes of venous thromboembolism is of primary importance for the diagnosis of familial thrombophilia. Since there is no validated method to diagnose past venous thromboembolism for epidemiologic purposes, the authors administered a questionnaire to a group of subjects who had had venous thromboembolism in the past and to a group of normal controls. Both cases and controls were less than age 65 years and were identified by the discharge diagnosis International Classification of Diseases codes of records of the Vicenza general hospital, Italy, from 1975 to 1992. Cases were further validated by critical review of pertinent medical records. For each key question, the sensitivity and specificity were computed; questions were then aggregated into sets of maximal sensitivity and specificity. The best diagnostic efficiency (98.2%) was obtained by a set of questions about past symptoms and anticoagulant treatment; this set showed a very high specificity (99.4%), but a low sensitivity (37.1%). A higher sensitivity (71.3%) was obtained without loss of specificity (98.9%) by retaining as positive those subjects who gave a history of venous thromboembolism and anticoagulant treatment or those who had a history of venous thromboembolism and venous reflux at Doppler ultrasound scanning but had no treatment. The combined use of the questionnaire and Doppler scan is suggested for epidemiologic surveys in population.

Female↗
PubMed1996

Interleukin-15 promotes the growth of leukemic cells of patients with B-cell chronic lymphoproliferative disorders.

The recently discovered cytokine, interleukin-15 (IL-15), has been demonstrated to share several biologic properties with IL-2 in different cell systems, including T-cell and natural killer (NK) cell compartments. As for B lymphocytes, IL-15 has been shown to provide stimulatory activities in normal preactivated B cells that are mainly transduced through IL- 2 receptor (IL-2R) complex components. Since leukemic B cells from patients with chronic lymphoproliferative disorders (CLD) bear IL-2R and grow in response to IL-2, we investigated whether IL-15 triggers the proliferation of malignant B cells obtained from 12 patients with B-cell chronic lymphocytic leukemia (B-CLL) and five patients with hairy cell leukemia (HCL). Enriched B cells recovered from five healthy subjects were also studied as controls. IL-15 stimulated the proliferation of freshly isolated leukemic B cells, but not resting normal B lymphocytes, the latter being able to grow in the presence of IL-15 only after in vitro preactivation with phorbol myristate acetate. The proliferation elicited by IL-2 on leukemic cells was comparable to that determined by IL-15. Following addition of graded concentrations of IL-15 to low/intermediate-dose IL-2, resting leukemic B cells showed a higher stimulatory rate than that observed using the two cytokines separately. In normal resting B lymphocytes, this cumulative effect was not observed. The role of different IL-2R subunits in IL-15-driven growth of malignant B cells was investigated both by their expression on leukemic cells and by the block of different IL-2R subunits (p55, p75, and p64) with specific monoclonal antibodies (MoAbs). Using flow cytometry and reverse transcriptase-polymerase chain reaction (RT-PCR) analyses we demonstrated that both B-CLL and HCL leukemic B cells express the beta and gamma chains of the IL-2R system. The stimulatory activity achieved by IL-15 decreased significantly, blocking the beta and gamma chains of the IL-2R. Taken together, these findings demonstrate that IL-15 triggers the growth of leukemic B cells through IL-2R system subunits, pointing to the role of this novel cytokine in regulating the neoplastic proliferation in CLD.

Adult↗
PubMed1996

Type I factor XIII deficiency is caused by a genetic defect of its b subunit: insertion of triplet AAC in exon III leads to premature termination in the second Sushi domain.

Factor XIII deficiency has been classified into two categories: type I deficiency, characterized by the lack of both the a and b subunits; and type II deficiency, characterized by the lack of the a subunit alone. To clarify the genetic bases of these diseases, previously reported cases of the type I deficiency were examined at the DNA level. DNA sequence analysis showed that a nucleotide triplet (AAC) was inserted within the codon for Tyr-80 in exon III of the gene for a female proband's b subunit, resulting in the creation of a stop codon. Restriction digestion of amplified DNAs confirmed that the proband and her sister were homozygotes, and their family members were heterozygotes of this mutant allele. A truncated protein composed of 79 amino acids could be synthesized by these homozygotes; however, such a protein would not be secreted or it would degrade quickly, because there were normal amounts of the mutant mRNA, but no b subunit was detected in these patients. The a subunit deficiency of these patients must be a secondary to the b subunit deficiency, as their gene for the a subunit was intact, and the a subunit in their platelets was present within normal levels.

Alleles↗
PubMed1996

Mutation pattern in clinically asymptomatic coagulation factor VII deficiency.

A total of 122 subjects, referred after presurgery screening or checkup for prolonged prothrombin time, were characterized for the presence of coagulation factor VII deficiency. Fourteen subjects carried a partial and asymptomatic deficiency, and in half of them dysfunctional molecules were detected in plasma. In nine subjects we found five missense mutations differing from those previously found in factor VII deficient patients. The others were homozygous for a common polymorphism (R353Q) that affects factor VII levels. A new codon dimorphism (A330) was also found in exon 8. Four mutations (R223W, M298I, R304Q, and R353Q) located at FVII-specific residues point out protein regions that are important for coagulation factor evolution, and two mutations (G342E and E265K) affect generic or partially generic residues. The newly reported mutations were combined with those we previously found, totalling 17 independent mutations responsible for FVII deficiency in 27 Italian pedigrees. We observed several similarities with the mutation pattern determined in factor IX, which include a high percentage of transitions at CpG doublets, the presence of hot spot sites affected by multiple substitutions, and of several topologically equivalent mutations.

Factor VII Deficiency↗
PubMed1996

Clinical usefulness of desmopressin for prevention of surgical bleeding in patients with symptomatic heterozygous factor XI deficiency.

Heterozygous factor XI (FXI) deficiency is sometimes associated with a significant bleeding tendency. Fresh frozen plasma of FXI concentrates are the mainstay of treatment in patients with a clear bleeding history, especially prior to surgery. However, these treatments are not completely free of risk. Furthermore, thrombosis has been reported in patients with FXI deficiency infused with FXI concentrate. No data are available on the possible efficacy of desmopressin in these patients. Two patients with a clear bleeding history associated with FXI deficiency and no additional haemostatic defects agreed to be treated with desmopressin before carpal tunnel surgery and dental extraction. The reduced basal FXI activity and antigen levels slightly increased after infusion, reaching borderline values. No bleeding was observed after surgical procedures. Desmopressin treatment seems a reasonable and useful choice in symptomatic, heterozygous FXI-deficient patients, thus reducing the cost of treatment, the risk of transmission of blood-borne viruses, and of thrombosis.

Blood Loss, Surgical↗
PubMed1996

A (15;17) translocation not associated with acute promyelocytic leukaemia.

We report a woman with acute myeloid leukaemia (AML) type M2 according to FAB classification, showing a t(15;17) apparently identical to that of acute promyelocytic leukaemia (APL) on conventional cytogenetic analysis. Fluorescence in situ hybridization (FISH) using cosmidic probes specific for RAR alpha and PML, regions did not show a fusion signal as in APL. The breakpoints were assigned to 15q24.3 and 17q21.1. Detailed molecular analyses did not reveal any involvement of RAR alpha and PML genes. The patient was resistant to several front-line AMI treatments and to all-trans retinoic acid (ATRA). These findings reinforce FISH and RT-PCR as useful tools for the characterization of a t(15;17) as the translocation specifically associated with APL.

Adult↗
PubMed1996

ETRO Working Party on Factor XIII questionnaire on congenital factor XIII deficiency in Europe: status and perspectives. Study Group.

A questionnaire was sent out in 1993 to more than 350 European institutions caring for patients with hemorrhagic disorders with the request to provide data of patients with congenital factor XIII deficiency, to pursue the following aims: (1) establish a registry of congenital factor XIII deficiency patients, (2) promote exchange between clinicians and basic researchers, (3) improve diagnostic and therapeutic approaches, and (4) stimulate research on gene defects and their impact on factor XIII function. So far, 72 patient questionnaires from 60 families have been collected. Their bleeding pattern is typical, with frequent involvement of the umbilical cord and the central nervous system. Forty-nine patients receive regular factor XIII replacement, but obviously some patients with mild symptoms do not require prophylactic substitution, despite low factor XIII levels. On the other hand, 18 patients had factor XIII activities of > or = 5% of normal, but only 3 of those patients were reported to have no bleeding symptoms. Furthermore, 17 symptomatic, apparently heterozygous relatives in eight families were observed. Seven out of 30 females aged over 18 years had experienced spontaneous abortions; wound healing problems were seen in 26 patients. Currently, a second questionnaire is being distributed to obtain more detailed information on bleeding and other symptoms, diagnostic approaches, and exclusion of concurrent other bleeding diatheses. Future activities will be validation and standardization of assays, and study of gene defects and their impact on the structure of factor XIII and symptoms of patients. We intend to expand the survey to countries outside Europe.

Abortion, Habitual↗
PubMed1996

Age-adapted moderate-dose induction and flexible outpatient postremission therapy for elderly patients with acute lymphoblastic leukemia.

We report the results of a recent trial in elderly acute lymphoblastic leukemia (ALL) patients (> or = 60 years). Initial chemotherapy consisted of one 14-day course with single-dose idarubicin plus vincristine-prednisone-L-asparaginase. Idarubicin was preferred to other anthracyclines because of its shorter time to response. Sequential outpatient postremission therapy included single-dose idarubicin plus vincristine-cyclophosphamide-L-asparaginase pulses, cranial irradiation with intrathecal methotrexate-cytarabine, flexible weekly vincristine-cyclophosphamide alternating with cytarabine-teniposide, and two-year standard maintenance with mercaptopurine-methotrexate. Granulocyte colony-stimulating factor (G-CSF) was added to induction and early consolidation courses. Twenty-two patients mainly with high-risk features entered the study: median age was 64 years (60-73), 40% of cases were CD10- B-lineage and T-lineage ALL, 38% of CD10+ B-lineage ALL carried a BCR-ABL rearrangement, while 23% coexpressed myeloid antigen, 86% had L2 morphology, 50% had a blast count greater than 10 x 10(9)/1, 54% had hepato-splenomegaly and lymphadenopathy. The complete remission (CR) rate after induction therapy was 59%. A partial remission was obtained in two cases. There were four early deaths (18%) and three refractory ALL (14%). Median time to response was 21 days. With G-CSF, the median duration of absolute neutropenia was 10.5 days. Flexible postremission therapy was very well tolerated, causing no major toxicity. With a median follow-up of 2.6 years, 3 patients remain alive in first CR (23%), 2 of whom at 21.3 months and 39.6 months, respectively. Median survival of responders was 12 months compared to only 1.2 months for nonresponders (p < 0.001). This moderate-dose idarubicin-containing and G-CSF-supported regimen was associated with a high early remission rate in elderly ALL. Postremission therapy results were modest, though not appreciably different from the general experience in this patient population. Because further escalation of drug intensity appears unjustified, attempts to document and reverse drug resistance patterns and restore a dysregulated apoptosis must be considered.

Aged↗
PubMed1996

The VITA Project: population-based distributions of protein C, antithrombin III, heparin-cofactor II and plasminogen--relationship with physiological variables and establishment of reference ranges.

A proper laboratory diagnosis of inherited thrombophilia due to defects of the coagulation system may be obtained only by a stringent definition of the diagnostic reference ranges taking into account the influence exerted by major physiological variables. To this purpose, we analyzed the data for Protein C, Antithrombin III, Heparin-Cofactor II and plasminogen coming from the first 4,000 subjects enrolled in the VITA Project. This is the first study that allows the establishment of reference ranges in a non-selected, active population using stringent standardization of clinical and laboratory measurements and multivariable regression techniques for data analysis. Serum triglycerides and total cholesterol, together with plasma fibrinogen were found to influence the functional plasma level of the four considered proteins. Menopause increased AT-III concentration, while pill use increased Heparin-Cofactor II and plasminogen. PT and PTT ratio, gender, age, smoking, body-mass index, HDL cholesterol and blood group had minor effects. The effect of these variables should be taken into account for both clinical and epidemiologic purposes, using appropriate reference ranges or covariance analysis for adjustment.

Adolescent↗
PubMed1996

Prospective multicenter study on subcutaneous concentrated desmopressin for home treatment of patients with von Willebrand disease and mild or moderate hemophilia A.

Desmopressin is the treatment of choice in most patients with von Willebrand disease (vWD) and mild hemophilia A (HA). Several studies have demonstrated that the intravenous and subcutaneous route of administration are equivalent in terms of pharmacokinetics and clinical efficacy. Home therapy of vWD and mild HA is desirable but so far there have been only a few case reports and no prospective studies. We report the results of a prospective study of home therapy in patients with vWD and mild-moderate HA using concentrated desmopressin self-administered subcutaneously. Clinical efficacy and safety were assessed by the patient using a questionnaire and direct interview. The patients were instructed on self-administration and dosage, reasons for treatment, recognition of side effects and recording clinical efficacy. The study lasted 12 months (range 6-17). During this time, 43/100 (43%) of the enrolled vWD patients (median basal VIII:C 24%, range 9-49) and 36/69 (52%) of HA patients (median basal VIII:C 10%, range 5-34) self-administered the drug. A total of 127 bleeding episodes requiring treatment occurred in patients with vWD and 92 in HA patients. There were 10 treatment failures of which 7 required in-hospital treatment. Overall, in 94% of treatments (excluding menorrhagia) the response was scored as excellent or good. In 86% of treated episodes of menorrhagia the response was scored as excellent or good. According to the patients, 81% of clinical situations would have required in-hospital treatment. Mild flushing, with or without headache, was the only consistent side-effect, reported in about 30% of treatments. In conclusion, home therapy with subcutaneous desmopressin for von Willebrand disease and hemophilia A was well accepted by the patients and proved feasible, efficacious and safe for the prevention or prompt treatment of bleeding.

Adolescent↗
PubMed1995

Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis.

BACKGROUND: Abnormalities in the number and function of platelets may contribute to thromboembolic complications in patients with essential thrombocythemia. We assessed whether maintaining the platelet count below 600,000 per cubic millimeter with hydroxyurea reduces the incidence of thrombosis in patients with essential thrombocythemia and a high risk of thrombosis. METHODS: A total of 114 patients with essential thrombocythemia (77 women and 37 men; median age, 68 years; range, 40 to 85) and a median platelet count of 788,000 per cubic millimeter (range, 533,000 to 1,240,000 per cubic millimeter) were randomly assigned to receive hydroxyurea (56 patients) or no myelosuppressive therapy (58 patients). Ninety-seven (85 percent) were over 60 years old, and 52 (46 percent) had had thrombosis. The two groups were matched for age, sex, and platelet count at randomization. Antiplatelet prophylaxis with aspirin or ticlopidine was not stopped. Follow-up lasted a median of 27 months in both groups. RESULTS: Two patients (3.6 percent) treated with hydroxyurea had thrombotic episodes (one stroke and one myocardial infarction), whereas 14 patients (24 percent) in the control group had thrombotic episodes (one stroke, five transient ischemic attacks, five peripheral arterial occlusions, one deep-vein thrombosis, and two cases of superficial thrombophlebitis). The difference (20.4 percentage points; 95 percent confidence interval, 8.5 to 32 percent) was statistically significant (chi-square with Yates' correction, 8.3; 1 df; P = 0.003). CONCLUSIONS: Hydroxyurea is effective in preventing thrombosis in high-risk patients with essential thrombocythemia.

Adult↗