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Biomedical subjects

T Barbui

Publications and source records attributed to T Barbui.

At least 145 records · Page 8Linked to original sources
PubMed1994

Different incidence of venous thrombosis in patients with inherited deficiencies of antithrombin III, protein C and protein S.

A cohort study was undertaken to compare the incidence of thrombosis in patients with inherited deficiency of Antithrombin III (n = 9), Protein C (n = 36) and Protein S (n = 36). The patients were stratified for schedule of antithrombotic prophylaxis and followed for a total period of 160 patient-years. Seven venous thrombosis were observed for a total incidence of 4.3% pts.-ys. The incidence of thrombosis was not significantly different in patients of different age, sex and schedule of prophylaxis, although there was a trend to a lower incidence in young individuals and in those receiving long-term oral anticoagulation. Patients with AT III deficiency had an higher incidence of thrombosis than patients with Protein C or Protein S deficiency (12 vs. 2.8 vs. 3.3% pts.-ys, p < 0.05), despite the fact that they were, on average, younger and more prophylaxed. This study suggests that congenital Antithrombin III deficiency constitutes a greater risk of thrombosis than congenital deficiencies of Protein C and Protein S.

Administration, Oral↗
PubMed1994

Cancer procoagulant in the human promyelocytic cell line NB4 and its modulation by all-trans-retinoic acid.

Acute promyelocytic leukemia (APL) cells express different types of procoagulant activity (PCA), including tissue factor (TF), and cancer procoagulant (CP). The aim of this study was to investigate whether the NB4 cell line, the first ever isolated human APL line, with the typical t(15;17) chromosomal balance translocation, possess CP as well as the cells freshly isolated from APL patients. Secondly, since the NB4 line is maturation inducible by all-trans-retinoic acid (ATRA), we wanted to verify whether CP, if present, was affected by ATRA treatment. The NB4 cells were able to shorten the recalcification assay of normal human plasma (total PCA). To distinguish CP in the assay for clotting activity, two criteria were used, the independence from factor VII to trigger blood coagulation and the sensitivity to cysteine proteinase inhibitors. Forty-seven per cent of total PCA of cell extracts was found to be FVII-independent PCA. A similar proportion of FVII-independent activity (42%) was detected in the cell serum-free supernatants. The activity was significantly decreased by cysteine proteinase inhibitors, including HgCl2, lodoacetic acid and Z-Ala-AlaCHN2. Additionally CP was directly identified and quantified by an immunocapture enzyme assay. The mean +/- SD concentration of CP detected by this assay in the NB4 cells, before any treatment, was 1.89 +/- 0.5 microgram/mg protein. Treatment of NB4 cells with 10(-6) M ATRA for 5 days significantly decreased the expression of CP, which became virtually undetectable by the clotting assay, and was 64% less than the untreated control by the immunocapture enzyme assay. This study provides the first evidence that the human promyelocytic cell line NB4 possess CP. The expression of this procoagulant is modulated by ATRA.

Blood Coagulation Factors↗
PubMed1993

Detection of ALL-1/AF4 fusion transcript by reverse transcription-polymerase chain reaction for diagnosis and monitoring of acute leukemias with the t(4;11) translocation.

The chromosomal breakpoints of t(4;11) translocation of acute lymphoblastic leukemia (ALL) have been recently identified at molecular level and shown to involve the AF4 (FEL) gene on chromosome 4 and the ALL-1 (MLL, Hrx) gene on chromosome 11. The ALL-1/AF4 fusion gene is transcribed into a chimeric mRNA. Using primer sets derived from ALL-1 and AF4 cDNAs by reverse transcription-polymerase chain reaction (RT-PCR), we were able to amplify the breakpoint sites of the fusion transcript of all 15 ALL cases with karyotypic or molecular evidence of the t(4;11). DNA fragments of different size were obtained as the consequence of different breakpoints on chromosome 11 and the presence of alternative splicing of ALL-1 exon 8. The feasibility of monitoring the residual cells carrying the t(4;11) in 2 ALL patients with different clinical outcome was evaluated. Overall, the presented results provide evidence that RT-PCR can be used as a rapid method for detecting this chromosomal abnormality and following the patient's response to therapy.

Adolescent↗
PubMed1993

Thrombotic and hemorrhagic complications in patients with mechanical heart valve prosthesis attending an anticoagulation clinic.

This study evaluated the advantage of an anticoagulation clinic in terms of the improvement of the clinical quality of oral anticoagulation (i.e. prevention of thromboembolism and low rate of hemorrhagic complications). The incidence of thromboembolic events and major hemorrhagic complications was assessed in a series of 271 patients on oral anticoagulation for mechanical heart valve prosthesis before and after their enrollment in our anticoagulation clinic from January 1987 to December 1990. Risk factors for hemostatic events were also analyzed. The incidence of major hemostatic complications was significantly lower when patients attended the clinic: 1.0 vs 4.9%/pt-yr for hemorrhage and 0.6 vs 6.6%/pt-yr for thrombosis. This depended on three main factors: better dose regulation of warfarin, continuous patient education and early identification of clinical conditions potentially at risk for thrombosis and hemorrhage. Only previous hemorrhagic or thromboembolic events were recognized as major risk factors for hemostatic complications. In conclusion, our study shows that an anticoagulation clinic offers a real advantage to patients with mechanical heart valve prosthesis in terms of prevention of thromboembolic events and hemorrhagic complications.

Administration, Oral↗
PubMed1993

Establishment and characterization of a new granulocyte-macrophage colony-stimulating factor-dependent and interleukin-3-dependent human acute myeloid leukemia cell line (GF-D8).

A novel factor-dependent human myeloid leukemia cell line (GF-D8) was established from the peripheral blood of an 82-year-old man suffering from acute myeloblastic leukemia (AML). By morphology, cytochemical staining, and analysis of surface antigens, GF-D8 cells are myeloblasts of immature progenitor origin. The consensus karyotype is 45, XY, -5, 7q-, inv(7) (q31.2q36), 8q+, +8q+, 11q+, 12p-, -15, -17, + marker. The long-term survival and proliferation of GF-D8 cells is dependent on the presence of either granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3). Weak colony growth was observed after exposure of GF-D8 cells to stem cell factor (SCF) but not after exposure to granulocyte-CSF (G-CSF), macrophage-CSF (M-CSF), IL-1 beta, IL-2, IL-5, or tumor necrosis factor-alpha (TNF-alpha). GM-CSF- and IL-3-induced proliferation is dose dependent, with significant growth observed at concentrations as low as 0.1 ng/mL, but the combination of both factors has no synergistic effect. A significant proliferation is induced by GM-CSF and IL-3 even in serum-deprived cultures, although with a slightly decreased efficiency. GF-D8 cells were shown to express specific messenger RNAs for the alpha chains of the GM-CSF and IL-3 receptors as well as for the beta chain, common to both receptors. Interestingly, despite the absence of biologic response to G-CSF, specific transcripts for the G-CSF receptor gene were similarly identified by reverse polymerase chain reaction analysis. GF-D8 cells represent a useful tool for studying chromosome abnormalities of human AML as well as the regulation of myeloid proliferation and differentiation in vitro.

Aged↗
PubMed1993

Supranormal antithrombin III levels induced by concentrate administration are ineffective in quenching thrombin generation in acute promyelocytic leukemia.

Coagulation abnormalities occurring in patients with acute promyelocytic leukemia (APL) are partially corrected by heparin administration. This study was undertaken to verify if "supra-normal" levels of antithrombin III (AT-III) are similarly able to quench intravascular thrombin generation triggered by APL cells. Eight patients with APL were randomly assigned to receive either 50 U/kg (Group A) or 100 U/kg (Group B) of an AT-III concentrate, starting on the first day of chemotherapy and continuing for 7 days thereafter. Fibrinopeptide A (FPA), prothrombin fragment F1+2 and thrombin-AT III complexes, measured before and 15 minutes after each AT-III infusion, decreased significantly after each infusion, but the effect was minimal and short-lived, despite the achievement of post-infusion levels of AT-III activity well above 150% (Group A) or 200% (Group B). Small amounts of heparin were consistently detected in AT-III concentrates and post-infusion plasma samples. The short-lived quenching of thrombin generation after AT-III concentrate could be partially explained by the infusion of heparin, rather than by supranormal AT-III levels.

Adult↗
PubMed1993

Nosocomial outbreak of severe Pseudomonas aeruginosa infections in haematological patients.

From June to September 1988, an outbreak of Pseudomonas aeruginosa infections in neutropenic patients admitted to the Haematological Wards of "Ospedali Riuniti" in Bergamo, Italy, was detected. Out of 11 cases of P. aeruginosa infections, 8 were bacteremic. Of these, 7 died within few days of onset (mortality rate: 87.5%). Consequently, possible sources of infection were investigated, and moist areas of the hospital environment were shown to be highly contaminated by P. aeruginosa. A clinical and microbiological follow-up of patients admitted to the Haematological Wards was performed for a 10 month period following the outbreak. Adequate measures for cleaning and disinfection were shown to reduce the frequency of P. aeruginosa hospital infections.

Adolescent↗
PubMed1993

Effect of antiphospholipid antibodies on procoagulant activity of activated platelets and platelet-derived microvesicles.

We have recently described the in vitro mechanism of action of anticardiolipin (aCL) and lupus anticoagulant (LA) antibodies in patients with the antiphospholipid syndrome. LA antibodies inhibit coagulation reactions in plasma because they appear to recognize the complex of lipid-bound (human) prothrombin, whereas aCL antibodies require beta 2-glycoprotein I (beta 2-GPI) for binding to anionic phospholipids. aCL antibodies can be divided into two subgroups, according to their behaviour in lipid-dependent coagulation reactions: aCL-type A enhances the anti-coagulant effect of beta 2-GPI, whereas aCL-type B does not. In the present study we investigated the effect of purified aCL-type A and B and of LA antibodies on the procoagulant activity of both Ca-ionophore activated platelets and platelet-derived microvesicles, using an assay system with highly purified bovine coagulation factors Xa, Va, and prothrombin from human and bovine origin. In the absence of beta 2-GPI neither type of aCL was able to inhibit the prothrombinase activity of platelets or microvesicles. However, a strong and dose-dependent inhibition of the prothrombinase activity of both platelets and platelet-derived microvesicles was observed within a few minutes, when aCL-type A antibodies were added in combination with beta 2-GPI. This inhibitory effect was dependent also on the concentration of beta 2-GPI. Conversely, no inhibitory effect of aCL-type B antibodies on platelet- (or microvesicle) prothrombinase activity in the presence of beta 2-GPI could be observed. LA antibodies were able to inhibit in a dose-dependent way the procoagulant activity of activated platelets and platelet-derived microvesicles. With two LA preparations this inhibition was only apparent when human prothrombin was used as substrate, while a third preparation exhibited its inhibitory effect both in the presence of human and bovine prothrombin. The data indicate that, in the presence of their respective cofactors beta 2-GPI and prothrombin, aCL and LA antibodies interact with the membrane of activated platelets and platelet-derived microvesicles in a very similar way as previously observed for their interaction with anionic phospholipid surfaces.

Adult↗
PubMed1993

Transcriptional and post-transcriptional regulation of IL-1 beta, IL-6 and TNF-alpha genes in chronic lymphocytic leukaemia.

The present study was designed to define the mechanisms of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and tumour necrosis factor (TNF-alpha) gene regulation in chronic lymphocytic leukaemia of B cell origin (B-CLL). By nuclear run-on analysis, all B-CLL cases displayed high levels of nuclear transcription of the IL-6 and TNF-alpha genes, whereas IL-1 beta gene transcription was only barely detectable. Upon in vitro culture for 1 h, B-CLL cells from different patients were substantially heterogeneous in terms of expression of steady state mRNA levels of IL-1 beta, IL-6 and TNF-alpha even though the pattern of nuclear transcription of these cytokines was only marginally affected by in vitro culture. mRNA stability was then examined and cytokine gene transcripts showed a half life of more than 2 h in cultured B-CLL cells and treatment with cycloheximide (CHX) did not affect cytokine transcript levels in B-CLL cells. These results indicate that: steady state levels of each mRNA do not reflect the rate of nuclear transcription of these cytokines in fresh or cultured B-CLL cells, that purification and in vitro culture of leukaemic cells may amplify cytokine gene expression in B-CLL, and that cytokine gene transcripts are relatively stable in B-CLL.

Blotting, Northern↗
PubMed1993

Cutaneous manifestations associated with antiphospholipid antibodies in patients with suspected primary antiphospholipid syndrome: a case-control study.

OBJECTIVE: To study the association of a variety of dermatological manifestations related to vascular abnormalities with antiphospholipid antibodies in patients with suspected primary antiphospholipid syndrome. METHOD: Case-control study. Consecutive patients referred to the coagulation and haemostasis service of a general hospital for the first determination of antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibodies) and newly diagnosed disorders (for example, thrombocytopenia, thrombotic disorders, and unexplained repeated abortions) were selected. Patients were examined by two dermatologists according to predefined criteria, and information about general characteristics and relevant dermatological and medical histories were collected using an ad hoc questionnaire. The study was limited to patients without evidence of systemic lupus erythematosus. A total of 35 patients was examined; 13 subjects were positive for lupus anticoagulant or anticardiolipin antibodies, or both (cases), and 22 were negative (controls). RESULTS: Moderate to severe livedo reticularis and acrocyanosis were significantly associated with antiphospholipid antibodies, with relative risks of 13.1 (95% confidence interval 1.1 to 149.0) and 8.6 (95% confidence interval 1.1 to 65.1). Capillaritis was also associated with the antibodies. Histories of Raynaud's phenomenon and superficial thrombophlebitis were more common in cases than controls. CONCLUSIONS: This study provides quantitative evidence of the association of antiphospholipid antibodies with several cutaneous diseases in which vascular abnormalities seem to play a major part. The study suggests that these manifestations might appear early in the development of the antiphospholipid syndrome.

Adult↗
PubMed1993

Clinical and biological effects of erythropoietin treatment of myelodysplastic syndrome.

To evaluate its clinical efficacy as well as its biologic safety, human recombinant Erythropoietin (rh-Epo) was given to 19 patients with myelodysplastic syndromes (MDS) in an open non-randomized study. Among the seventeen evaluable patients only two showed an apparent hematologic response to rh-Epo treatment. In these patients hemoglobin levels increased from a mean pretreatment value of 8.5 and 8.4 g/dl up to 11.7 and 11.3 g/dl respectively and remained relatively stable for several weeks. In one of these patients the transfusion requirement decreased from 4 to 1.5 units per month whereas the other had no transfusion requirement during the whole period of rh-Epo treatment. Interestingly, when the responding patients, after a "wash-out" period of at least ten weeks, received an additional course of rh-Epo results were less impressive. Before treatment the serum level of endogenous Epo was 18 and 110 mU/ml in the two responding patients, whereas a mean value of 532 mU/ml (range 17-2797 mU/ml) was observed in non responders. The treatment of MDS patients with rh-Epo was clinically well tolerated since no relevant side effects were registered. Moreover, no evidence of harmful cytogenetic changes nor activation of myeloid growth factor genes, as determined by Northern blot analysis of GM-CSF and G-CSF gene expression, could be related to rh-Epo treatment. Overall, it appears that administration of rh-Epo is well tolerated but the therapeutic effects appear to be restricted to a minority of patients and a limited period of time.

Aged↗
PubMed1993

Modulation of cell proliferation and cytokine production in AML by recombinant interleukin-1 receptor antagonist.

In Acute Myelogenous Leukemia (AML), Interleukin 1 (IL-1) might sustain autocrine and paracrine loops of leukemic growth. An IL-1 inhibitor has been recently purified and cloned. This molecule binds to the IL-1 receptors but has no IL-1 like activity fulfilling the characteristics of a pure Interleukin-1 receptor antagonist (IL-1ra). We studied the in vitro effect of human recombinant IL-1ra on proliferation of AML blasts. Spontaneous as well as IL-1 stimulated AML proliferation was significantly inhibited by the addition of 50 ng/ml of recombinant IL-1ra in a dose dependent manner. The inhibitory effect of IL-1ra was measurable after 12 hours of culture and reached a plateau at 60 hrs. We found that IL-1ra could compete with IL-1 in binding to specific IL-1 receptors on AML cells. As expected, culture supernatants of unstimulated leukemic samples contained IL-1 beta and GM-CSF activity. The incubation of the same leukemic blasts with IL-1 ra was followed by reduction or disappearance of GM-CSF in culture supernatants whereas the IL-1 beta production was only partially modulated. By Northern blot experiments performed on freshly isolated, uncultured leukemic blasts, we found a constitutive expression of the IL-1 beta gene in 19 of 23 AML cases analyzed. On the contrary, only three of these patients express the IL-1 RA mRNA. All together these results suggest that imbalanced secretion of IL-1 and its natural receptor antagonist could contribute to the unrestricted growth of AML cells.

Cell Division↗
PubMed1993

Human T-cell lymphoblastic lymphoma expressing the T-cell receptor gamma/delta established in immune-deficient (bg/nu/xid) mice.

A small subgroup of human CD3-positive T-cell lymphoblastic lymphoma (T-LL) has been recently identified to express the T-cell receptor (TCR) gamma/delta heterodimer. Moreover peculiar clinical and histologic patterns of spleen and liver involvement have been associated with the TCR gamma/delta phenotype of tumor cells. In this paper we describe a human T-LL cell line (LL-DP) established in beige-nude-xid (BNX) mice, that by immunophenotype, molecular, and karyotype analyses, maintained most of the features of the patient. After serial transplants in BNX mice, LL-DP acquired quite a stable phenotype, producing a visible tumor in about 5 weeks in all the intravenously injected animals. The minimum number of transplanted cells that produce a tumor in all mice is 1 x 10(6). BNX mice bearing LL-DP lymphoma cells presented marked abdominal distension and splenomegaly. Diffuse lymphadenopathy with large tumor deposits in various lymph nodes that produce architectural effacement with a diffuse growth pattern was documented. The bone marrow was completely replaced, and spleen, liver, and kidneys were involved. Invasion of the central nervous system was leptomeningeal and perivascular. Overall this model might be useful for understanding mechanisms supporting lymphoma growth and progression as well as for testing new therapeutic strategies.

Adolescent↗
PubMed1992

Prolonged bleeding time in patients with lupus anticoagulant.

Platelet adhesion to collagen under flow conditions was studied in 18 patients with lupus anticoagulant, seven of which showed a prolonged bleeding time in the presence of a normal platelet count. The effect of patient plasma, IgG and purified anticardiolipin antibodies on platelet adhesion was also examined. We found a significant reduction of platelet adhesion in patients with lupus anticoagulant, which was more evident in patients with prolonged bleeding time. This platelet adhesion defect could be attributed to a plasma factor. In fact, patients' platelets regained normal adhesion when mixed with normal plasma, whereas controls' platelets showed abnormal adhesion in the presence of patient plasma. A causative role of antiphospholipid antibodies was demonstrated in experiments using purified immunoglobulins and anticardiolipin antibodies.

Adult↗