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Biomedical subjects

T Barbui

Publications and source records attributed to T Barbui.

At least 217 records · Page 12Linked to original sources
PubMed1988

Increased response to arachidonic acid and U-46619 and resistance to inhibitory prostaglandins in patients with chronic myeloproliferative disorders.

In patients with myeloproliferative disorders (MPD) a group of related diseases of the bone marrow stem cell and recurrent haemorrhagic and/or thrombotic complications, the production of aggregating prostaglandins (PGs) may be normal or slightly reduced, while PGI2 production is normal. However, MPD platelet sensitivity to antiaggregatory PGs is still unknown. We studied the potency of PGD2, PGI2 and PGE1 as inhibitors of platelet aggregation induced by threshold aggregating concentrations of arachidonic acid and U-46619-analogue of the cyclic endoperoxide PGH2 in 20 patients with MPD in comparison with healthy controls, with the aim of evaluating the sensitivity of MPD platelets to antiaggregatory PGs. In these patients platelet prostanoid metabolism was normal. However, the functional response of platelets to aggregating and antiaggregating prostanoids was shifted towards potentially increased platelet aggregation response. These findings could have a clinical relevance in view of the haemostatic and thrombotic complications so frequent in MPD.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1988

Association of large granular lymphocyte/natural killer cell proliferative disease and second hematologic malignancy.

We describe the first three patients with a large granular lymphocytosis/lymphocytic leukemia and another blood malignancy. In two, a myeloproliferative disorder developed soon after the diagnosis of abnormal proliferation of large granular lymphocytes-natural killer (LGL-NK) cells, a myelodysplastic syndrome evolving to acute leukemia and a Philadelphia-positive chronic myelogenous leukemia. In these cases, LGLs expressed the phenotype of CD3+ NK and CD3- NK cells, respectively, and were clonal in the first patient as demonstrated by T-cell receptor gene rearrangement study. In the third case, a similarly clonal excess of LGLs, phenotypically CD3+ NK cells, was detected following a diagnosis of B-cell hairy-cell leukemia. Clinically, the concurrence of LGL proliferation and other leukemia did not seem to confer a worse prognosis on the patients. Although an association by chance remains a possible explanation, a common origin from an altered precursor cell for both myeloid and LGL proliferations in the first two cases is discussed, whereas in the third it might be related to the severe immune derangement frequently observed in hairy-cell leukemia.

Adult↗
PubMed1988

Therapeutic efficacy of danazol in myelodysplastic syndromes.

Sixteen unselected untreated patients with primary myelodysplastic syndromes (MDS) and various combinations of blood cytopenia were treated with danazol, an attenuated androgen reported to be of some value in these conditions. After a 12 week trial (danazol 600 mg/day/p.o.), anaemia improved in 4/14 patients, with transfusional requirements being reduced by 50% or more in four other cases (response 57%). An enhanced reticulocyte production was documented in 6/13 cases (46%), and thrombocytopenia resolved in 5/8 (62%). Results of the granulocyte count were less satisfactory, with only one partial response obtained among five cases. A normalization of the monocyte count was seen in 3/5 patients with chronic myelomonocytic leukaemia, with one of them achieving a complete haematological and clinical remission lasting 6 months. Circulating blast cells decreased significantly (50% or more) in 4/6 cases. Although clinical symptoms from anaemia and bleeding disappeared in responsive cases, four patients developed acute non-lymphocytic leukaemia. Danazol was well tolerated and produced no acute or chronic toxicity. The drug appears useful in the management of anaemic and thrombocytopenic MDS patients.

Aged↗
PubMed1988

Investigation of chronic lymphocytosis in adults.

Thirteen cases of idiopathic chronic lymphocytosis are the subject of this report. Patients showed a lymphocyte count between 4 and 15 X 10(9)/L for at least six months, marrow lymphocytosis not exceeding 25%, absence of lymphomegaly and hepatosplenomegaly, and no associated infections, immune, or neoplastic disease. Morphologic examination of smears revealed a lymphocytosis of large granular lymphocytes in five. A selected battery of polyclonal and monoclonal antisera to antigens commonly found on B-, T-, and natural killer cells allowed the identification of six cases of early B-cell chronic lymphocytic leukemia, two cases of T-cell lymphocytosis with a suppressor or helper T-cell phenotype, and five cases of large granular lymphocyte/natural killer cell proliferative disease. The results demonstrate the usefulness of combining morphologic and phenotype studies for the investigation of chronic lymphocytosis, which often appears as an early leukemia or a benign clonal proliferative disorder of lymphocyte subsets.

Adult↗
PubMed1988

In vitro platelet adhesion to vascular subendothelium: studies in patients with polycythaemia vera.

In this work we studied platelet adhesion to subendothelial surfaces in 10 patients with polycythaemia vera and 10 healthy volunteers at 40% Hct (corresponding to the mean value of our control group) and 55% Hct (a value roughly corresponding to the mean Hct in polycythaemic patients). Platelet concentration was kept constant at 2.0-2.5 X 10(11)/l. The results indicate that there was a statistically significant increase in adhesion both in controls and in patients with Hct varying from 40% to 55%. The contribution of the higher Hct in promoting platelet adhesion was comparable in the two groups. When red blood cells (RBC) from the patients were tested with platelets from healthy volunteers in cross-over experiments, they promoted adhesion in the same way as control RBC. Similarly, when patients' platelets were mixed with control RBC, adhesion was the same as control platelets. These data indicate that platelet and RBC contribution to this parameter are not significantly modified in this group of polycythaemic patients, provided that platelet and RBC values are adjusted to control range.

Adult↗
PubMed1988

Interaction between platelets and lupus anticoagulant.

10 consecutive patients fulfilled the diagnostic criteria for lupus anticoagulant. 4 had concomitant systemic lupus erythematosus, 1 Waldenstrom's disease and 5 had no apparent underlying disease. Only the case with Waldenstrom's disease presented a bleeding tendency, with bleeding time greater than 20 min; the others had a history of thrombotic complications. A defect of platelet aggregation induced by ADP, epinephrine, collagen and arachidonic acid was documented in the Waldenstrom's disease case whose lupus anticoagulant was an IgM. In the others, lupus anticoagulant, identified as IgG immunoglobulins, produced no aggregation abnormalities. However, beta-thromboglobulin levels in platelets, plasma and urine were consistent with a pattern of platelet activation in all cases. IgG immunoglobulins separated from sera of 6 patients showed lupus anticoagulant activity, with no effects on platelet aggregation of normal platelet-rich plasma, but they induced secretion of beta-thromboglobulin from normal platelets.

Adult↗
PubMed1988

Antiphospholipid antibodies in early repeated abortions: a case-controlled study.

The relation among lupus anticoagulant (LAC), anticardiolipin antibodies (ACA), and repeated abortions was evaluated in a case-controlled study of 49 women with two or more unexplained spontaneous abortions (cases) compared with 141 control subjects, who had had one or more normal pregnancies and no previous spontaneous abortion. The women were admitted to the same hospital where the cases had been identified for acute conditions other than immunologic neoplastic, gynecologic or cardiovascular. LAC was detected in 7 out of 49 cases (14%, 95% confidence limits 8% to 26%) but in none of the 141 controls. Similarly, ACA were detected in four cases (8%, 95% confidence limits 0.3% to 30%) but no controls. These differences in frequency were statistically significant. These findings confirm that LAC and ACA are associated with a history of repeated abortions in clinically asymptomatic patients for immunologic conditions.

Abortion, Habitual↗
PubMed1988

Inhibition of ticlopidine of platelet adhesion to human venous subendothelium in patients with diabetes.

To elucidate the bleeding tendency that follows the administration of ticlopidine, we investigated the skin bleeding time and some ex vivo functions of platelets from nine patients with insulin-dependent diabetes before and 2 weeks after daily doses of 500 mg ticlopidine. Ticlopidine significantly prolonged bleeding time and reduced platelet reactivity to fixed, relatively high concentrations of aggregating agents, without interfering with thromboxane B2 formation. We used a rotating probe device at a relatively low shear rate (570 sec-1) to measure platelet adhesion to human subendothelium. This system was able to detect an impairment of platelet adhesion dependent on glycoprotein (GP) Ib defect (Bernard Soulier syndrome) or on low platelet von Willebrand factor content, but was insensitive to platelet GPIIb-IIIa defect (Glanzmann's thrombasthenia). In our patients, platelet adhesion was consistently reduced after the administration of ticlopidine. We conclude that ticlopidine is an inhibitor of platelet function that modulates the interaction between platelets. The drug also appears to interfere with mechanisms that modulate platelet-subendothelium interaction at relatively low shear rates. This double action could be relevant in the prevention of vasculopathy in patients with diabetes.

Adult↗
PubMed1988

A new procoagulant in acute leukemia.

To verify whether cancer procoagulant (CP), a cysteine proteinase procoagulant distinct from tissue factor (TF), is associated with leukemic cells, we assayed the procoagulant activity of blast cell extracts from 26 patients with different cytological subtypes of acute nonlymphoid leukemia (ANLL) according to the French-American-British classification. All the samples except two shortened the recalcification time of normal human plasma, the effect being significantly greater in the M3 subgroup. The two criteria used to distinguish between CP and TF, independence from factor VII in initiating blood coagulation and sensitivity to cysteine-proteinase inhibitors, were positive in 19 samples from M1, M2, M3, and M4 cytological subtypes. None of the M5 samples fulfilled these criteria. In addition, M1, M2, M3, and M4 samples immunoreacted with an anti-CP goat polyclonal antibody on an Ouchterlony immunodiffusion plate. This study provides the first evidence for a procoagulant other than TF that is associated with leukemic cells.

Acute Disease↗
PubMed1987

Aspirin and risk of bleeding in patients with thrombocythemia.

Thirty-two patients with thrombocythemia associated with myeloproliferative syndromes were selected on the basis of normal bleeding time and absence of hemorrhagic or thrombotic history. Twenty-five control subjects were studied simultaneously. They were all given a single intravenous infusion of 500 mg of aspirin (lysine acetylsalicylate), and bleeding time was measured two hours later. Both in the control group and in the patient group, aspirin significantly prolonged the bleeding time, but the average prolongation was significantly more pronounced in the patients. In comparison with the control subjects, the patients had a statistically significant reduction of platelet serotonin content and no difference in the production of platelet lipoxygenase derivative 12-HETE or plasma von Willebrand factor properties. Fourteen patients had abnormal platelet aggregation in response to adenosine diphosphate, adrenaline (epinephrine), or collagen. In six of them, all with very low serotonin content, the bleeding time was prolonged above the upper limit of the post-aspirin values in the control group. Thus, cyclooxygenase inhibition by aspirin unmasked a bleeding tendency in patients with a severe reduction in platelet dense bodies content. These findings might be relevant in relation to the use of antiplatelet drugs.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1987

Treatment of the lymphoid blast crisis of chronic myeloid leukemia.

Ten patients with lymphoid-type blast crisis of chronic myeloid leukemia were treated with combination chemotherapy comprising doxorubicin, vincristine, L-asparaginase, and prednisone. Once remission was achieved in 9 (90%), consolidation with doxorubicin, vincristine and cyclophosphamide was given, and then maintenance chemotherapy with 6-mercaptopurine and methotrexate. Median remission duration was 12 months (range 2-18) and survival 17 (range 3-29). Drug-related toxicity was manageable, leading to a major schedule alteration in 3 cases. These data suggest that combination chemotherapy including doxorubicin improves the prognosis of lymphoid blast crisis in chronic myeloid leukemia.

Adult↗
PubMed1987

T cell receptor (alpha, beta, gamma) gene rearrangements and expression in normal and leukemic large granular lymphocytes/natural killer cells.

The large granular lymphocyte (LGL) population, which effects a natural killer (NK) function, consists of cells whose lineage derivation has not been clearly established on the basis of phenotypic and functional properties. To clarify the relationship of LGL/NK cells to T cells we studied patterns of rearrangement and expression of the T cell receptor (Ti) genes alpha, beta, and gamma in normal human LGLs; in CD8+, CD8-, Mol+, and Mol- LGL subsets; and in 17 cases of leukemic LGL proliferations (T gamma LPD). T alpha, T beta, and T gamma genes were not expressed, nor were T beta and T gamma genes rearranged in normal LGLs or LGL subsets. The T gamma LPD were divided into two groups. One group (15/17 cases) was characterized as CD3+ and displayed Ti gene rearrangements. Seven of these cases were reactive with monoclonal antibody WT31, which suggested expression of an alpha/beta heterodimer on the cell surface. The other group (2/17 cases) was CD3- with unrearranged Ti genes. These results indicate that the normal LGL/NK population is homogeneous and distinct from the normal T cell population because it does not express, and as a result, cannot effect its immune function through the T cell receptor molecules. Conversely, T gamma LPDs represent a heterogeneous group of lymphoproliferative diseases within which the CD3-, Ti- cases most likely represent the neoplastic counterpart of normal LGL cells. The more frequent CD3+ cases may be related to recently described NK-like T cells. The observations that normal LGLs maintain germline T gamma genes and that many CD3+ T gamma LPD display an alpha/beta heterodimer suggest that a T gamma-containing receptor may not be necessary for NK or NK-like cytotoxicity.

Antigens, Surface↗