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Biomedical subjects

J M Moraleda

Publications and source records attributed to J M Moraleda.

At least 55 records · Page 3Linked to original sources
PubMed1996

Allogeneic peripheral blood progenitor cell transplantation: analysis of short-term engraftment and acute GVHD incidence in 33 cases. allo-PBPCT Spanish Group.

The results of 33 allogeneic peripheral blood progenitor cells transplants (allo-PBPCT) in adult patients with hematologic malignancies were analyzed in a retrospective and multicenter study. In 21 of 33 cases (63%) the disease was refractory or in advanced stage and eight of the 33 cases (24%) were second transplants after relapse. Donors were treated with a median of 10 (4-16) micrograms/kg/day of rhG-CSF subcutaneously for 5-7 days. Three required a central venous line for harvesting. Peripheral blood leukapheresis product contained a median of 5.9 (1.8-13) 10(6)/kg CD34+ cells and a median of 309.5 (153-690) 10(6)/kg CD3+ cells. After a myeloablative regimen, all patients received PBPC from HLA-identical donors as the sole source of progenitor cells. Cyclosporin A (CsA) alone (n = 2), CsA and steroids (n = 9), and CsA and methotrexate (MTX) (n = 22) were used for GVHD prophylaxis. Growth factors post-transplant were given to 11 patients (33%). The median follow-up of the patients was 3 months. Actuarial median day for hemopoietic recovery was: neutrophils to >0.5 (>1) x 10(9)/l, day 14 (15); platelets to >20 (>50) x 10(9)/l, day 14 (21). The quantity of CD34+ cells infused did not significantly affect the engraftment kinetics, from a starting cutoff of 2.5 x 10(6)/kg. The speed of neutrophil recovery seemed to be influenced strongly by using rhG-CSF post-transplant and marginally by the type of GVHD prophylaxis. Actuarial probability for grade II-IV acute GVHD of the whole group was 37% (95% Cl, 20-54%).

Actuarial Analysis↗
PubMed1995

[The follow-up of the mobilization of circulating hematopoietic progenitor cells by granulocyte growth factor (G-CSF) using flow cytometry].

BACKGROUND: The aim of the present study was to investigate the characteristics of the mobilization of hematopoietic precursor cells CD34+ in peripheral blood following stimulation with recombinant granulocytic colony stimulating factor (G-CSF). METHODS: Fourteen patients (10 males, 4 females: mean age 33 years; range 14-58 years) diagnosed with oncohematologic neoplasms, in complete remission were studied. The patients had not received antineoplastic for at least four weeks prior to inclusion in the study. Recombinant G-CSF (8 micrograms/kg) was administered subcutaneously over a minimum of 4 days. Peripheral blood control were performed prior to administration of G-CSF (day 0), the third (day +3) day, and the sixth day (day +6). Daily leukapheresis was initiated at day +3 in 5 patients and at day +4 in 9 patients. The CD34+ cell content was determined in both peripheral blood and leukapheretic material by flow cytometry with an anti CD-34 monoclonal antibody conjugated with fluorescein. RESULTS: No significant differences were observed between the mononuclear cells and CD34+ counts obtained at the first apheresis and those performed at days +3 or +4 (32 +/- 14 x 10(9) vs 29 +/- 19 x 10(9) and 240 +/- 125 x 10(6) vs 162 +/- 160 x 10(6), respectively). The content of the apheresis products in CD34+ cells correlated positively with the number of these cells circulating in peripheral blood (r = 0.53, p = 0.001). In the second apheresis, the presence of mononuclear cells decreased approximately 20% with respect to the first, remained constant in later collections. To the contrary, a constant maintained decrease was observed in the collection of CD34+ on each leukaphesis in that the fourth apheresis only contributed in approximately 10% of the total quantity of CD34+ cells collected. CONCLUSIONS: Maximum mobilization of precursor cells was achieved on the third day at a dosage of 8 micrograms/kg/day, with the data found suggesting that three leukapheretic procedures are enough to collect most of the CD34+ cells mobilized.

Adolescent↗
PubMed1995

Cryopreservation modifies flow-cytometric analysis of hemopoietic cells.

Although cryopreservation of human bone marrow has become very common in modern medicine, the knowledge on the effects of this procedure on hemopoietic cells is still limited. We herein have investigated whether the process of concentrating of human bone marrow to its buffy coat, the exposure to the cryoprotectant dimethyl sulfoide (DMSO), and/or the rate of controlled freezing/thawing procedures modifies the flow cytometric analysis of human bone marrow cells. We found that both the exposure of marrow cells to DMSO and/or the freezing procedure significantly modifies both the relative proportions of hemopoietic cell subsets and the intensity of expression of certain surface antigens. Thus, percentages of cells expressing CD7, CD13, CD33 and CD34, were found to be lower in both cryopreserved buffy coat and buffy coat merely exposed to DMSO, in comparison to those in untreated coat samples. Moreover, the intensity of the surface expression of CD33 decreased in cells exposed to DMSO, and further in cryopreserved samples. By contrast, the intensity of the CD19 antigen was higher in the last groups of samples than in the buffy coat or the unfractionated human bone marrow. Our present results suggest that flow-cytometric analysis of cryopreserved human bone marrow cells is not fully equivalent to that corresponding to fresh bone marrow or its fractionated buffy coat.

Antigens, CD↗
PubMed1994

Quantitative defect of glycoprotein Ib in severe cirrhotic patients.

A decrease of platelet agglutination induced by ristocetin has been described in cirrhotic patients. In order to investigate the relationship of such phenomenon with a putative defect on platelet membrane glycoprotein Ib, we have studied the quantitative and functional status of Gp Ib in eleven severe alcoholic cirrhotic patients, and the ability of their formalin-fixed platelets to agglutinate in the presence of normal plasma plus ristocetin. Interestingly, we found a significant decrease of immunoreactive GP Ib molecules (9,978 +/- 1,534 vs. 17,064 +/- 404 molecules per platelet) and ristocetin-dependent binding of vWF (9,113 +/- 1,338 vs. 13,992 +/- 1,968 molecules per platelet) (P < 0.01) in comparison to the levels found in a control group of healthy subjects. Immunoblotting analysis of platelet lysates confirmed the reduction of GP Ib level in cirrhotic patients, but showed no modification on the precipitation pattern of this glycoprotein. The ristocetin-induced platelet agglutination (light transmission %) was also significantly lower in patients with cirrhosis (48 +/- 7.6 vs. 92 +/- 3.6, P < 0.01), and correlated with the binding of normal vWF (r = 0.863, P = 0.0013). Patients with bleeding times longer than 7 min and/or clinical history of bleeding episodes showed the lowest values of platelet agglutination and GP Ib level. In conclusion, our present results indicate that liver cirrhosis is associated with a relevant decrease of functional GP Ib molecules on the platelet surface. This reduction might be related to the prolongation of bleeding time and to the bleeding diathesis observed in cirrhotic patients.

Adult↗
PubMed1994

Stability of glycoproteins Ib/IX and IIb/IIIa during preparation and storage of platelet concentrates: detection by binding assays with epitope-defined monoclonal antibodies and physiological ligands.

Preservation of the glycoprotein (GP) complexes Ib/IX and IIb/IIIa, because of their role as specific platelet receptors for adhesive proteins, is essential for the haemostatic efficacy of transfusions of platelet concentrates (PCs). We have combined binding assays with epitope-defined monoclonal antibodies, and with the physiological ligands von Willebrand factor and fibrinogen (Fo), to investigate the total expression and functional status of these receptors, in PCs stored for up to 9 days. Routine preparation and storage for up to 5 days have no apparent effect on the surface expression and the functional status of GPs Ib/IX and IIb/IIIa. However, after prolonged storage for up to 9 days we found a 50% decrease in the level of the total and functional GP Ib/IX content of platelets. This finding parallelled a significant rise in plasma glycocalicin, a proteolytic fragment of GP Ib. In addition, long-term storage promoted an impairment in the exposure of GP IIb/IIIa to Fo, and a 50% decrease in Fo binding capacity, without affecting the complex quantitatively. Finally, we also noticed a storage-induced increase in the platelet surface expression of GMP 140, and after 9 days of storage there was a rise in mean platelet volume, and a significant reduction in pH levels.

Agglutination Tests↗
PubMed1993

Repeated infusions of DDAVP induce low response of FVIII and vWF but not of plasminogen activators.

Although the vasopressin analogue desamino-d-arginine vasopressin (DDAVP) induces a very well characterized increase in factor VIII (FVIII), von Willebrand factor (vWF), tissue plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA), the mechanism(s) by which DDAVP enhances the plasma levels of these proteins is poorly understood. Some clinical evidence suggests that certain patients repeatedly treated with DDAVP at closely spaced intervals become progressively unresponsive (tachyphylaxis). In order to investigate the effect of repeated DDAVP infusion on the behaviour of FVIII, vWF, t-PA and u-PA, we infused three different doses of DDAVP (0.3 microgram/Kg) to six healthy volunteers (19-26 years old, mean 22) at 12-hour intervals. Blood samples were collected immediately before and after DDAVP. The second and third infusion of DDAVP induced a low response of FVIII and vWF. In contrast, t-PA and u-PA exhibited a consistent response after each DDAVP infusion. If the progressive decrease of FVIII and vFW response observed in healthy subjects after repeated doses of DDAVP at 12-hour intervals is extended to haemophiliacs and von Willebrand's patients, the usefulness of desmopressin may be limited when these proteins must be raised therapeutically for a prolonged period of time. Finally, our results suggest that the mechanism for regulating the release of vWF and plasminogen activators in the conditions of our study are not dependent.

Adult↗
PubMed1991

[Clinico-hematological characteristics of acute transformation of chronic myeloproliferative syndromes].

BACKGROUND: The aim of the present study was to analyze the blastic transformation occurring during chronic myeloproliferative diseases (CMPD) and to establish the differences between them. METHODS: The clinical and hematological characteristics of 54 patients in blastic crisis (BC) of a CMPD were analyzed: 40 chronic myelogenous leukemias (CML), 9 idiopathic myelofibroses (IMF), 4 polycythemia vera (PV), and one essential thrombocythemia (ET). The results were analyzed by the BMDP statistical program. RESULTS: The BC of CML appeared in younger patients (p less than 0.05). Only in this group did some patients achieve complete remission. Moreover, in this BC a greater incidence of visceromegalies and leukocytoses were observed. The BC of the IMF patients led to marked anemia (p less than 0.01) and bone marrow infiltration (p less than 0.05); these leukemias were more frequent in males and began with lymphadenopathies and visceromegalies. The transformations of PV were preceded by a longer chronic phase and had a lower incidence of visceromegalies and a nearly normal hemoglobin count value. The patient with acute leukemia secondary to ET did not display visceromegalies but did have anemia, leukopenia and a normal platelet count. None of the four groups responded to therapy, and their survival was short. CONCLUSIONS: Blast transformations of different myeloproliferative disorders have their own idiosynchratic clinical and hematological characteristics, some of these may be related to the chronic phase of disease.

Age Factors↗
PubMed1990

[Non-traumatic rupture of the spleen in malignant hemopathies. 2 new cases].

Spontaneous splenic rupture is an unusual complication of hematologic malignancies with a high mortality rate. We report two cases of non-traumatic splenic rupture: the first one was a patient with myelomonocytic leukaemia and the second one a previously undiagnosed patient with non Hodgkin's lymphoma, both of them survived after splenectomy. Emphasis on the necessity of an early diagnosis and treatment are made.

Aged↗
PubMed1990

Surface phenotype and immunoglobulin levels in B-cell chronic lymphocytic leukaemia.

The aim of the present study is to analyze the relationship between serum immunoglobulin (Ig) levels and the immunological phenotype and the clinicohaematological features of B-cell chronic lymphocytic leukaemia (B-CLL) in a series of 126 patients. Eighty-eight of the cases (70%) had a decreased concentration of at least one Ig. IgM and IgA were the most frequently decreased (60% and 49% respectively). A serum monoclonal gammapathy was found in 4 patients, Ig M/k in two cases and IgM/l and IgG/k in one case. Patients with hypogammaglobulinaemia had a similar surface phenotype as patients with normal Ig levels (MRFC+, sIg+, CD20+, HLA/DR+, FMC7-, CD5+, CD9+). On the other hand the cases with hypogammaglobulinaemia displayed the features of a more advanced disease, a higher incidence of organomegalies (p less than 0.05), anaemia and/or thrombopenia (p less than 0.05), a diffuse bone marrow pattern (p less than 0.05), advanced clinical stages (p less than 0.05) as well as higher levels of both peripherial blood (p less than 0.02) and bone marrow lymphocytosis (p less than 0.02). These findings suggest that the presence of hypogammaglobulinaemia in B-cell patients is probably more related to a higher tumor burden than to either certain stages of B-cell differentiation or a particular cellular phenotype.

Agammaglobulinemia↗
PubMed1988

A randomized trial comparing chlorambucil plus prednisone vs cyclophosphamide, melphalan, and prednisone in the treatment of chronic lymphocytic leukemia stages B and C.

Ninety-six previously untreated patients (67 males/29 females; mean age: 63 years; range: 46-84) with CLL in stage B (62 cases) or C (34 cases) were randomized to be treated with either chlorambucil (0.4 mg/kg orally days 5 and 6) plus prednisone (60 mg/m2 orally days 1 to 4) (CL + PDN) every 2 weeks or cyclophosphamide (160 mg/m2 orally days 1 to 4), melphalan (6 mg/m2 orally days 1 to 4), and prednisone (60 mg/m2 orally days 1 to 4) (CMP) every 3 weeks for 10 months. Forty-eight patients were treated with CLR + PDN, and the remaining 48 with CMP. The following types of response were considered: complete response (CR): total disappearance of symptoms and signs related to the disease. Partial response (PR): shift of the disease to a less advanced stage. Stable disease (SD) no change in the stage after treatment. Progressive disease (PD): progression of the disease to a more advanced stage. Thirty-six (75%) responses (27% CR) with CLR + PDN and 26 (54.5%, 12.5% CR) with CMP were observed (p = 0.054). Although more responses were achieved in stage B (69%, 24% CR) than in stage C (54%, 12% CR) this difference did not achieve statistical significance. Survival was statistically not different for those patients treated with LCR + PDN as compared to those receiving CMP.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗