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Biomedical subjects

T Barbui

Publications and source records attributed to T Barbui.

At least 127 records · Page 7Linked to original sources
PubMed1995

Autologous PBSC transplant for late onset AML after mafosfamide-purged and TBI-containing autologous BMT.

The prognosis of AML patients who fail autologous BMT and lack a donor for a salvage allogeneic BMT is very poor. We administered an alternative drug treatment including autologous PBSC transplant to a child who relapsed with AML 4 years after a mafosfamide-purged and TBI-containing BMT for second remission AML. Treatment comprised induction-consolidation with 'short' ICE courses (idarubicin-Ara C-etoposide for 2 days), high-dose CY plus G-CSF with collection of CD34+ PBSC and myeloablative treatment with high-dose mitoxantrone/BEAM supported by autologous PBSC reinfusion. The outcome was complete response, lasting 24 months. The patient died in remission of drug-related cardiotoxicity. This report emphasizes the possibility of a secondary AML after mafosfamide-purge autologous BMT, and documents the feasibility of an autologous PBSC transplant in such a high risk setting.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Short-term treatment for adult hypergranular and microgranular acute promyelocytic leukemia.

A high hemorrhagic risk and a complete response to the differentiative agent all-trans-retinoic acid (ATRA) are the main clinical features of acute promyelocytic leukemia (APL), two distinct subtypes of which have been recognized, the common hypergranular leukopenic form (M3) and a microgranular hyperleukocytic variant (M3v). We analyzed, with emphasis on both disease- and therapy-related prognostic factors, the results from a 9-year trial in 65 adults with M3 and M3v APL, treated homogenously with a short-term therapy (STT) program excluding maintenance. STT comprised a maximum of six courses with doxorubicin, cytosine arabinoside (ara-C), and 6-thioguanine. Sixty-five APL patients formed the study group, M3v accounting for 25% of cases. In M3v, the absolute blast cell count was significantly higher (p < 0.0001) and early hemorrhagic deaths were more frequent (p = 0.05). The blast count correlated inversely with the probability of remission (p = 0.005), poor-risk patients being those with > 10 x 10(9)/l blast cells. During the study, the median survival improved from 0.1 to 2.7 years (p = < 0.005). In first place, response to chemotherapy increased from 42 to 84% (p = 0.006), by giving daily prophylactic platelet transfusions (to > 30 x 10(9)/l) and no heparin (course I), and by avoiding too toxic high-dose ara-C and deferring treatment in infected/neutropenic patients showing the atypical differentiative bone marrow pattern (course II). Secondly, the probability of first unmaintained remission differed significantly between patients given intentionally more than four total chemotherapy courses or intermediate/high-dose ara-C consolidation (0.59 at 5 years) and those treated less intensively (0.21) (p < 0.005). Intensive STT was very effective for the management of adult APL patients at standard hemorrhagic risk and receiving optimal supportive care. In high-risk patients with hyperleukocytosis and M3v, induction results could be improved by the concomitant use of ATRA. M3v in adults must be recognized promptly because of the very high early hemorrhagic risk.

Adolescent↗
PubMed1995

Clinical coagulation laboratory and oral anticoagulant therapy treatment. Instrumentation and methodology.

To assess the organization and the quality of care of an anticoagulation clinic, the structure, the process of laboratory control and the clinical outcome in our Center are described. 1068 patients under control in 1994 (M/F 572/496; median age 63 range 6-91 ys., 74% in long-term prophylaxis) were evaluated. The clinic was run twice weekly by a physician, two nurses and a technician; management for emergencies was always warranted. Prothrombin time was carried out with a sensitive thromboplastin (ISI < 1.1) and a computer program provided calculation and graphical representation of INR, comparison with therapeutic range, automatic dosage prescription and print out. Laboratory quality of therapy was assessed by three different techniques: 'cumulative INR', 'last check in file' and 'linear change', yielding respectively 69% of laboratory controls, 71% of patients and 80% of days within the therapeutic range. The rate of thrombosis, major and total bleeding were respectively 0.2%, 0.2% and 12.5%. An anticoagulation clinic represents an effective organizational model for the management of patients taking oral anticoagulants.

Administration, Oral↗
PubMed1995

Increased thromboxane biosynthesis in essential thrombocythemia.

In order to investigate the in vivo thromboxane (TX) biosynthesis in essential thrombocythemia (ET), we measured the urinary excretion of the major enzymatic metabolites of TXB2, 11-dehydro-TXB2 and 2,3-dinor-TXB2 in 40 ET patients as well as in 26 gender- and age-matched controls. Urinary 11-dehydro-TXB2 was significantly higher (p < 0.001) in thrombocythemic patients (4,063 +/- 3,408 pg/mg creatinine; mean +/- SD) than in controls (504 +/- 267 pg/mg creatinine), with 34 patients (85%) having 11-dehydro-TXB2 > 2 SD above the control mean. Patients with platelet number < 1,000 x 10 (9)/1 (n = 25) had significantly higher (p < 0.05) 11-dehydro-TXB2 excretion than patients with higher platelet count (4,765 +/- 3,870 pg/mg creatinine, n = 25, versus 2,279 +/- 1,874 pg/mg creatinine, n = 15). Average excretion values of patients aging > 55 was significantly higher than in the younger group (4,784 +/- 3,948 pg/mg creatinine, n = 24, versus 2,405 +/- 1,885 pg/mg creatinine, n = 16, p < 0.05). Low-dose aspirin (50 mg/d for 7 days) largely suppressed 11-dehydro-TXB2 excretion in 7 thrombocythemic patients, thus suggesting that platelets were the main source of enhanced TXA2 biosynthesis. The platelet count-corrected 11-dehydro-TXB2 excretion was positively correlated with age (r = 0.325, n = 40, p < 0.05) and inversely correlated with platelet count (r = -0.381, n = 40, p < 0.05). In addition 11 out of 13 (85%) patients having increased count-corrected 11-dehydro-TXB2 excretion, belonged to the subgroup with age > 55 and platelet count < 1,000 x 10(9)/1. We conclude that in essential thrombocythemia: 1) enhanced 11-dehydro-TXB2 excretion largely reflects platelet activation in vivo; 2) age as well as platelet count appear to influence the determinants of platelet activation in this setting, and can help in assessing the thrombotic risk and therapeutic strategy in individual patients.

Adult↗
PubMed1994

Preventing fungal infection in neutropenic patients with acute leukemia: fluconazole compared with oral amphotericin B.

OBJECTIVE: To compare the efficacy and tolerability of fluconazole and oral amphotericin B in preventing fungal infection in neutropenic patients with acute leukemia. DESIGN: A randomized, controlled, multicenter trial. SETTING: 30 hematologic units in tertiary care or university hospitals. PATIENTS: 820 consecutive, afebrile, adult patients with acute leukemia and chemotherapy-induced neutropenia. INTERVENTION: Patients were randomly assigned to receive fluconazole, 150 mg, as a once-daily capsule, or amphotericin B suspension, 500 mg every 6 hours. MEASUREMENTS: An intention-to-treat analysis was done for 820 patients: 420 treated with fluconazole and 400 treated with oral amphotericin B. RESULTS: Definite systemic fungal infection occurred in 2.6% of fluconazole recipients and 2.5% of amphotericin B recipients; suspected systemic fungal infection requiring the empiric use of intravenous amphotericin B occurred in 16% of fluconazole recipients and 21% of oral amphotericin B recipients, a difference of 5 percentage points (95% CI for difference, -0.02% to 10%; P = 0.07). Superficial fungal infection was documented in 1.7% of fluconazole recipients compared with 2.7% of amphotericin B recipients, a difference of one percentage point (CI of difference, -0.9% to 3%; P > 0.2). The distribution of fungal isolates in systemic and superficial fungal infection was similar in both groups. The overall mortality rate accounted for 10% in both groups. An excellent compliance was documented for 90% of patients treated with fluconazole compared with 72% of those treated with amphotericin B suspension, a difference of 18 percentage points (CI for difference, 13% to 23%). Side effects were documented less frequently in fluconazole than in amphotericin B recipients (1.4% compared with 7%, a difference of 5.6 percentage points; CI for difference, 2% to 8%; P < 0.01). CONCLUSION: Fluconazole was at least as effective as oral amphotericin B in preventing systemic and superficial fungal infection and the empiric use of amphotericin B in neutropenic patients with acute leukemia but was better tolerated.

Acute Disease↗
PubMed1994

Retinoic acid and granulocyte colony-stimulating factor synergistically induce leukocyte alkaline phosphatase in acute promyelocytic leukemia cells.

In this report we show a strong synergistic interaction between granulocyte colony-stimulating factor (G-CSF) and all-trans retinoic acid (ATRA) on the expression of leukocyte alkaline phosphatase (LAP) in freshly isolated acute promyelocytic leukemia (APL) blasts as well as in NB40 and HL-60 cell lines. The strong synergism observed in these cell types was not evident in two acute leukemia cell lines (K562 and GF-D8), in normal granulocytes, and in monocytes. In freshly isolated leukocytes derived from chronic myelogenous leukemia (CML), in the stable phase of the disease, a weaker interaction between ATRA and G-CSF was documented. The cross-talk between the cytokine and the retinoid was studied in detail in NB4, an immortalized APL leukemia cell line, retaining the 15-17 chromosomal translocation involving the retinoic acid receptor type alpha. The treatment of NB4 cells with G-CSF alone or ATRA alone leads to no increase and to minor induction in LAP activity, respectively. If the cells are treated with the two compounds simultaneously, a dramatic elevation of LAP is observed after 4 days. The synergism between G-CSF and ATRA is evident at concentrations of the retinoid between 10(-7) and 10(-5) mol/L and at concentrations of the cytokine between 1 and 10 ng/mL. The simultaneous presence of the two compounds is necessary to obtain maximal increase of LAP activity and the effect is cell density-dependent. Synergism is specific for G-CSF, and it is not observed with other cytokines and functional inducers of the granulocyte. The augmentation of LAP activity is the consequence of an increased transcriptional rate of the liver/bone/kidney-type (L/B/K-type) alkaline phosphatase gene, as determined by Northern blotting and nuclear run-on analysis using specific cDNA probes. Only one of the two possible alternatively spliced forms of L/B/K-type alkaline phosphatase transcript is detected in NB4 cells after stimulation with G-CSF and ATRA. This mRNA form, which is the one observed in normal polymorphonuclear leukocytes, contains the most upstream leader exon. In NB4 cells, ATRA induces G-CSF, alpha, and beta retinoic acid receptor transcripts, whereas G-CSF has minor effects on the expression of these mRNAs.

Alkaline Phosphatase↗
PubMed1994

Essential thrombocytemia and ischemic stroke: report of six cases.

Essential thrombocytemia (ET) is a clonal myeloproliferative disorder of unknown cause, characterized by an increased number of apparently normal platelets. It has been related to a large number of mild ischemic complications, but rarely to acute stroke associated with documented large vessel thrombosis. We report the cases of 6 patients with acute ischemic stroke associated with ET (4 men and 2 women; mean age 61.7: range 49-78 years). The diagnosis of ET followed the onset of the stroke. The number of platelets was never greatly increased at the time of the stroke, and two patients presented no major risk factors for stroke. The involvement of the posterior circulation was observed in three patients, that of the anterior circulation in two patient and that of the border territory in one. The obstruction of large intracranial or extracranial vessels was detected in all of the patients, and all of them were treated with antiplatelet agents (aspirin or ticlopidine). The outcome was good in 3 patients, fair in one and bad in two. We retain that ET might be a cause of acute ischemic stroke as a result of large vessel obstruction.

Aged↗
PubMed1994

Hemostatic system activation in patients with lupus anticoagulant and essential thrombocythemia.

Hemostatic system activation was estimated in the plasmas of 39 patients with LAC and 19 patients with ET by measuring concentrations of TAT complex and prothrombin F1+2. The concentrations of FVII, recognized previously as a risk factor for arterial thrombosis, were also measured. None of the patients had active thrombosis during this study. The mean TAT and F1+2 levels in LAC and ET plasmas were higher than the respective values in the plasmas of healthy control subjects. Compared with their respective controls, TAT levels were significantly higher in the LAC group (P < 0.05) and F1+2 was significantly higher in the ET group (P < 0.005). The mean FVIIt and FVIIz was significantly higher (P < 0.05 and P < 0.01, respectively) in LAC than control plasmas. Furthermore, the differences between FVIIt and FVIIz were significantly greater in LAC than control plasmas, indicating increased in vivo proteolysis of FVII in LAC. Although the mean concentrations of these two FVII parameters in ET plasma were not significantly different from those of normal plasmas, the FVII levels were higher in 30% of ET plasmas than the upper limit of controls. Our results are consistent with hypercoagulation in LAC and ET patients, and this may be a contributory factor for the increased rates of thrombosis associated with the two conditions.

Adolescent↗
PubMed1994

The hypercoagulable state in cancer patients: evidence for impaired thrombin inhibitions.

Activation of prothrombin and the subsequent reactions of thrombin with its substrates and its major inhibitors, antithrombin III (AT III) and heparin cofactor II (HC II), likely reflect both intravascular and extravascular coagulation. Several studies have reported increased in vivo coagulation in cancer. Whether the increased thrombin production in malignancy is accompanied by a corresponding increase in thrombin inhibition is unknown. This study quantified prothrombin fragment 1 + 2 (F1 + 2), thrombin-AT III (TAT), thrombin-AT III-vitronectin (TAT.V), and thrombin-HC II-vitronectin (THCII.V) in the plasmas of healthy volunteers (n = 37); patients with localized solid tumours before treatment was initiated (n = 39); and five patients with non-Hodgkin's lymphoma, both before and during weekly chemotherapy. Two of the five non-Hodgkin's lymphoma patients developed deep venous thrombosis (DVT) during chemotherapy. In normal plasma, where the concentrations of the four parameters likely reflect haemostasis, the sum of TAT, TAT.V and THCII.V was 61% that of F1 + 2, compared with 30% in cancer plasmas. In addition, the mean +/- SEM of F1 + 2 in the plasmas of cancer patients (1.56 +/- 0.09 nM) was significantly elevated (P < 0.001) when compared with healthy volunteers (0.89 +/- 0.06 nM). Eight weeks of chemotherapy increased the F1 + 2 and the binary TAT in plasmas of the non-Hodgkin's lymphoma patients by approximately 1.5- and 2.9-fold, respectively. Thus, increased prothrombin activation in cancer patients, without corresponding increases in concentrations of thrombin-inhibitor complexes, raise the possibility that a significant portion of the thrombin generated in vivo escapes inhibition in cancer and contributes to the high risk of DVT in malignancy.

Adult↗
PubMed1994

Further characterization of platelet-aggregating cysteine proteinase activity in thrombotic thrombocytopenic purpura.

Circulating platelet-aggregating activities have been described by several authors. In a previous study we have confirmed the presence in serum and plasma from patients with thrombotic thrombocytopenic purpura (TTP) of a platelet aggregating cysteine proteinase (PACP). This activity differed in that, among the class of thiol enzymes, it showed characteristics of a lysosomal cathepsin rather than of a cytoplasmic calpain. To further investigate the enzymatic properties of this PACP we have designed a study to evaluate the dependence of the activity on Ca++. Calcium-dependence is a property of calpains but not of cathepsins. A proteolytic assay was set up and conducted with and without Ca++. The release of acid-soluble peptide from denatured human globin promoted by TTP samples and standards was fluorimetrically measured. The results show that TTP samples were equally active with and without Ca++ similar to standard papain (the cathepsin B-like proteinase), whereas standard calpain only acted with Ca++. An inhibition study performed by the proteolytic assay confirmed the same pattern of sensitivity of PACP to a series of specific cystein proteinase inhibitors previously shown by the proaggregating assay. The enzymatic behaviour of PACP of TTP resembled a lysosomal (cathepsins) rather than a cytoplasmic (calpains) cysteine proteinase.

Calcium↗
PubMed1994

Unexpected remission of acute myeloid leukaemia after GM-CSF.

The administration of granulocyte-monocyte colony-stimulating factor (GM-CSF) was associated with complete clinical and haematological response in an adult patient with minimally differentiated acute myeloid leukaemia who presented with pneumonia and moderate neutropenia, but no blast cells in the peripheral blood. The response lasted 9 months. At relapse, a second GM-CSF course resulted in a very good partial remission lasting 5 months, although differences in the kinetics of haemoglobin, neutrophil and platelet recovery were noted. Subsequent recurrences were managed with chemotherapy, a complete remission being obtained twice more and lastly consolidated with myeloablative chemo-radiotherapy supported by a peripheral blood stem cell autograft. This report suggests that GM-CSF should be further investigated as a therapeutic agent in selected cases of AML.

Acute Disease↗
PubMed1994

Recombinant versus high-sensitivity conventional thromboplastin: a randomized clinical study in patients on oral anticoagulation.

A prospective, randomized, double-blind clinical trial was carried out in a single center to compare the clinical and laboratory quality of oral anticoagulant therapy monitored with recombinant tissue factor (RTF) or with a sensitive, human-derived, conventional thromboplastin (CT) in the PT test. Seven hundred and fifty-seven consecutive patients receiving oral anticoagulation for various indications were randomized to RTF (n = 379) or CT (n = 368) for 6 months. Total follow-up was 167 and 153 patient-years for RTF and TP groups respectively. Fifty-six bleeding events were observed: 31 in the RTF group and 25 in the TP group. The incidence of bleeding was 18.5 and 16.5% pt-yrs for RTF and TP patients respectively (n.s.). The event-free follow-up curves were not significantly different between the two groups. The laboratory quality of oral anticoagulation was evaluated with the "last check in file" method: therapeutic INR was found in the same proportion of RTF and TP patients (70.2% vs 68.8%). Our study shows that RTF is as effective as a sensitive, conventional thromboplastin for monitoring oral anticoagulation.

Administration, Oral↗
PubMed1994

Clinical manifestations and management of inherited thrombophilia: retrospective analysis and follow-up after diagnosis of 238 patients with congenital deficiency of antithrombin III, protein C, protein S.

The clinical history of 238 patients with inherited thrombophilia (AT III = 94, PC = 103, PS = 41) was analyzed retrospectively at diagnosis and in the follow-up period after diagnosis. At diagnosis 129 patients (54%) had suffered from thrombosis, with a recurrence rate of 48%. The most frequent onset manifestation was deep vein thrombosis of lower limbs (58%). Thrombotic history started before 40 in 80% of the cases. Forty-nine percent of the venous thromboses were preceded by a triggering event, in most cases pregnancy (17%) and surgery (12%). After diagnosis, follow-up lasted a total of 1,113 pt-years. A policy of short-term prophylaxis during risk situations for all patients and long-term prophylaxis in symptomatic patients failed to prevent venous thrombotic episodes (diagnosed by objective methods) in 4 previously asymptomatic subjects and recurrence in 7 previously symptomatic subjects. After knowledge of the patients' diagnosis the incidence of venous thrombosis/100 pt-years was reduced as compared before diagnosis as total episodes (onset+recurrencies) (1.0 vs 1.9), onset episodes (0.7 vs 1.3) and recurrent episodes (1.3 vs 4.8), even though the differences were not statistically significant. However most of the venous thromboses occurred at a more advanced age (67% after 40 years) and without any apparent cause (83%), at significant variance with the period preceding the diagnosis; in particular the incidence of venous thrombotic onset in patients younger than 40 passed from 1.3/100 pt-years to 0.2/100 pt-years. In 6 recurrences after diagnosis a poor compliance for antithrombotic treatment was recognized.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Anti-glycoprotein Ib/IX and IIb/IIIa antibodies in patients with antiphospholipid antibodies.

Antiphospholipid antibodies, namely lupus anticoagulant (LA), anticardiolipin (aCL) type A and type B antibodies, are frequently associated with immune-mediated thrombocytopenia. Antiphospholipid antibodies have been suggested to bind to the phospholipids of the platelet membrane, thus participating to the process of platelet destruction, which leads to thrombocytopenia. However, a clear antiphospholipid (aPL) demonstration of such a role has never been given for antibodies. Conversely, autoantibodies directed against membrane-associated glycoproteins (GP) have been shown to be pathogenetically linked to the development of thrombocytopenia in patients with idiopathic thrombocytopenic purpura. For this reason, we have measured anti-GPIb/IX and GPIIb/IIIa IgG in the plasma of 68 patients with aPL antibodies by ELISA. The monoclonal antibody-specific immobilization of platelet antigen (MAIPA) assay was used. Twenty-seven out of 68 patients with antiphospholipid antibodies (40%) had increased plasma levels of anti-GP antibodies. In particular, 7 of them had elevated anti-GPIIb/IIIa levels only, 6 had anti-GPIb/IX antibodies only, whereas in the remaining 14 cases both types of autoantibodies were found elevated. The level of anti-GP antibodies in plasma did not correlate with age, sex, clinical associated conditions, history of thrombosis, IgG aCL titer or the presence of a phospholipid-dependent inhibitor of coagulation. In contrast, a statistically significant association between thrombocytopenia and high anti-GP antibody titer was observed (p = 0.0458). To establish whether there was cross-reactivity between antiphospholipid and anti-GP antibodies, adsorption experiments were performed using cardiolipin-containing liposomes or washed, normal, resting platelets.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗