Disseminated aspergillosis after mobilization with intensive chemotherapy prior to autologous stem-cell transplant in chronic myeloid leukemia.
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Adult↗
Biomedical subjects
V Vicente
Publications and source records attributed to V Vicente.
The venous thrombosis risk factor 20210 A allele of the prothrombin gene is not a major risk factor for arterial thrombotic disease.
A nucleotide change (G to A transition) at position 20210 has recently been demonstrated to be a risk factor for venous thrombosis. The relevance of this polymorphism to thrombotic disease was investigated by genotypic identification in three prospective case-control studies: 101 case patients with acute coronary heart disease (CHD), 104 patients with acute cerebrovascular disease (CVD), 82 patients with a confirmed diagnosis of deep venous thrombosis (DVT), and one control age- and sex-matched for each patient. The prevalence of the genetic variation was significantly associated with the occurrence of DVT, but did not differ in patients with CHD or CVD from that in controls, suggesting that this allele should not be considered a major risk factor for arterial thrombotic disease.
Adult↗
Prospective randomized study comparing the efficacy of bioequivalent doses of glycosylated and nonglycosylated rG-CSF for mobilizing peripheral blood progenitor cells.
Thirty patients diagnosed with breast cancer were included in a prospective randomized study comparing the in vivo priming effect of bioequivalent doses of glycosylated (lenograstim) and nonglycosylated (filgrastim) rG-CSF administration. Analysis of the efficacy of equivalent biological doses of both rG-CSFs showed no significant differences either in the mobilization of the subpopulations of PBPC considered (CD34+, CD34+/38-, CD34+/DR-), the content of such CD34+ cell subsets in the leukapheresis product, or the cost of the mobilization and collection procedures between both recombinant molecules. These results suggest that priming with bioequivalent doses of the two commercially available forms of glycosylated or nonglycosylated rG-CSF has a similar in vivo effect on PBPC mobilization.
Adult↗
Loss of high-affinity thrombin receptors during platelet concentrate storage impairs the reactivity of platelets to thrombin.
BACKGROUND: The storage of platelet concentrates (PCs) induces a reduction in the platelet surface expression of glycoprotein (GP) Ib alpha. The location of the platelets' high-affinity binding site for thrombin has been postulated as being located on GPIb alpha. This study attempts to determine whether loss or alteration of GPIb alpha during storage of PCs is related to impairment in the reactivity of platelets to thrombin. STUDY DESIGN AND METHODS: In this study, platelet surface expression of GPIb alpha was monitored by means of flow cytometry, throughout standard storage of PCs for up to 10 days. Two thrombin-induced platelet responses, the binding of radiolabeled fibrinogen and the platelet surface expression of P-selectin, were evaluated. Thrombin-binding assays were also performed to assess the number of thrombin receptors in platelets. RESULTS: The surface expression of the GPIb/IX complex declines during storage of PCs. The thrombin-induced maximal binding of fibrinogen in platelets stored for 3, 7, and 10 days was 77 +/- 7 percent, 60 +/- 20 percent, and 34 +/- 25 percent, respectively, of that found in fresh platelets. Moreover, the concentration of thrombin needed for 50 percent of platelets to express the CD62 antigen P-selectin at the surface increased from 0.05 U per mL in fresh platelets to 0.11, 0.56, and 1.2 U per mL in platelets stored for 3, 7, and 10 days, respectively. Thrombin-binding experiments demonstrated a significant reduction in the number of high-affinity binding sites throughout storage of PCs (55 +/- 21 sites/platelet in 10-day-stored platelets vs. 73 +/- 25 in fresh platelets). A significant correlation was also observed between the number of high-affinity thrombin-binding sites and surface expression of GPIb alpha. Selective blockage of the thrombin-binding site on GPIb alpha with monoclonal antibody LJ-Ib10 also inhibited the response of fresh platelets to thrombin, up to a level equivalent to that found in 3-day-stored platelets. CONCLUSION: The loss of the GPIb alpha-located high-affinity thrombin-binding site may impair the ability of platelets to become activated by thrombin as storage time increases.
Antibodies, Monoclonal↗
HPA-1 genotype in arterial thrombosis--role of HPA-1b polymorphism in platelet function.
Recently, the HPA-1b (PlA2) polymorphism of the platelet glycoprotein IIIa has been suggested as a genetic risk factor for coronary artery disease. We conducted two case-control studies of 103 patients with ischaemic cerebrovascular disease (CVD) and 101 patients with ischaemic heart disease (IHD). The groups were matched for age, race and sex. No significant differences regarding selected risk factors (hypertension, diabetes mellitus, hypercholesterolaemia and smoking) were found between case patients and controls. Moreover, we investigated 286 normal individuals from the Mediterranean area. Genotyping of HPA-1 was performed by PCR-allelic specific restriction and single-strand conformation polymorphism analysis. The prevalence of HPA-1b was similar among case patients and controls (29.2% vs. 25.3% and 26.7% vs. 34.6% for CVD and IHD case-control studies, respectively). The HPA-1b allele was found in 36.4% of the normal population. Finally, the analysis of platelet function in nine controls with the three possible HPA-1 genotypes (three a/a, three a/b and three b/b) indicates that HPA-1b genotype does not modify either the in vitro platelet aggregation and activation profile, nor the GP IIb/IIIa interaction with fibrinogen or von Willebrand factor. Our results do not support the role of HPA-1b polymorphism as an inherited risk factor for arterial thrombotic disease.
Adult↗
[Autologous transplant with BEAM protocol in lymphoma].
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Adult↗
[Other congenital hypercoagulable states].
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Afibrinogenemia↗
[Economic costs of autotransplantation of hematopoietic progenitors].
BACKGROUND: A comparative analysis of the economic costs of the different methods of autologous transplantation was carried out. METHODS: A series of 22 patients was retrospectively studied: 8 treated with autologous bone marrow transplantation (ABMT), 9 treated with peripheral blood stem cell (PBSC) transplantation and 5 in whom mixed transplantation of bone marrow and peripheral blood hematopoietic progenitors was performed. The expenses derived from pretransplant studies and from the collection of hematopoietic progenitors and from the autologous transplantation procedure itself were evaluated. RESULTS: The pretrasplant study and the collection of hemopoietic progenitors were significantly more expensive in the PBSC than in the ABMT (p = 0.04 and p = 0.007, respectively). Nonetheless, the costs of the transplant procedure were lower in the PBSC than in the ABMT group although the differences were not statistically significant. The estimated costs of these procedures in the Hematology Unit of the General Hospital of the University of Murcia, Spain, is of 3 million pesetas for the ABMT and 2.5 million for the PBSC. The greatest cost observed in the ABMT was due to these patients requiring longer hospitalization, greater transfusion support and longer antibiotic treatment. CONCLUSIONS: Although the collection of hematopoietic progenitors and pretransplant evaluation are less expensive in autologous bone marrow transplantation, the early morbidity is higher than that of peripheral blood stem cell transplantation or mixed autotrasplanted of bone marrow and circulating progenitors thus resulting in higher costs.
Adolescent↗
Association of autoantibodies against platelet glycoproteins Ib/IX and IIb/IIIa, and platelet-reactive anti-HIV antibodies in thrombocytopenic narcotic addicts.
The levels of platelet-associated Igs (PAIgs) and plasma circulating antiplatelet antibodies were evaluated by a flow cytometric immunofluorescence assay (FCIFA), an enzyme-linked immunoassay (ELISA), and a platelet radioactive antiglobulin test (PRAT), in a group of 45 human immunodeficiency virus (HIV)-infected intravenous drug users (IVDUs), with or without thrombocytopenia (TCP). Direct tests demonstrated an increased amount of PAIgs in 40% of the patients, irrespective of their platelet count. These PAIgs were mainly of IgG class and could not be eluted with ether. Plasma IgG with antiplatelet activity was found in 70% of the thrombocytopenic individuals, whereas it was detected in only one patient without TCP. The relative frequencies of antibodies against the platelet glycoproteins (GPs) Ib/IX and IIb/IIIa were assessed in plasma from all patients by means of the monoclonal antibody-specific immobilization of platelet antigens assay (MAIPA). Plasmas from all non-thrombocytopenic patients were negative when tested by indirect MAIPA. In contrast, 10/23 plasma from thrombocytopenic patients reacted with either GP IIb/IIIa, GP Ib/IX, or both GPs. Finally, aiming to investigate whether HIV antibodies from these patients are reactive with normal platelets, we performed absorption-elution experiments, followed by evaluation of HIV antibodies in the indirect eluates by ELISA and Western blot. Interestingly, we detected anti-HIV antibodies that bind to normal platelet antigens in 50% of the ether eluates prepared from control platelets sensitized with plasma from patients with TCP, but in only 5% of eluates obtained from platelets sensitized with plasma from non-thrombocytopenic patients. The present study provides direct evidence that specific autoantibodies against platelet membrane GPs Ib/IX and IIb/IIIa are common in HIV positive thrombocytopenic individuals. The finding in these patients of HIV antibodies cross-reactive with normal platelets, suggests that mimicry of human antigens by HIV could play a key role in the pathophysiology of the HIV-related TCP.
Adult↗
Immune recovery after autologous or rhG-CSF primed PBSC transplantation.
We performed a prospective study in 17 consecutive patients following Autologous bone marrow (BM) or rhG-CSF primed peripheral blood item cell (PBSC) transplantation, with the objective of comparing immune recovery between both procedures and to evaluate results in rhG-CSF mobilized peripheral blood stem cell transplantation (PBSCT). Kinetics of immune reconstitution showed differences, with a faster recovery of CD3+ and CD8+ T cells, and a more rapid and sustained recovery of CD8+/-/CD56+ natural killer (NK) cells in the PBCSCT group. Autologous bone marrow transplantation (ABMT) was associated with a improved reconstitution of the CD19+/CD5+/-subpopulation. Moreover, rhG-CSF mobilized PBSCT generated a greater recovery of CD8+/-/CD56+ cells than previous data concerning transplantation with peripheral blood (PB) progenitors collected after myelosuppressive chemotherapy or myelosuppressive therapy plus rhG-CSF. Our results show differences in the rate and pattern of B and T lymphocytes reconstitution after ABMT and PBSCT. Additionally, we state an enhancement of CD56+ cells in patients undergoing PBSCT mobilized solely using rhG-CSF.
Adolescent↗
Quantification of circulating activated protein C in human plasma by immunoassays--enzyme levels are proportional to total protein C levels.
We have developed a simple assay that measures the circulating activated protein C (APC) in plasma. The assay requires collection of duplicate blood samples, one in citrate plus heparin and the other in citrate plus inhibitors of the enzyme. In the heparin tube, APC reacts completely and irreversibly with its major plasma inhibitors, protein C inhibitor (PCI) and alpha 1-antitrypsin (alpha 1AT), and the complexes formed are measured by ELISAs. The amount of circulating APC is calculated from the difference between the total amount of complexed APC (sample in citrate plus heparin) and the amount of APC complexed in vivo (sample in citrate plus inhibitor). Over 95% of the APC added to blood collected with heparin was recovered in the assay. The assay can easily be performed in four hours, and had a detection limit of 0.1 ng/ml APC. The mean APC level in 18 protein C heterozygous members from seven kindreds was significantly lower (0.6 +/- 0.3 ng/ml) than in 20 healthy controls (1.1 +/- 0.3 ng/ml) (p < 0.001), whereas the mean level in 10 non-affected members from the kindreds studied was 1.5 +/- 0.3 ng/ml. In the group of 12 nonanticoagulated heterozygous protein C-deficient individuals, the three patients with a history of venous thrombosis had a mean APC level significantly lower than the nine asymptomatic members (p < 0.01), both subgroups showing similar protein C levels. There was a significant correlation in all groups between the levels of APC and the levels of protein C antigen (r = 0.758, p < 0.0001) and activity (r = 0.745, p < 0.0001), which means that APC circulating levels are proportional to protein C levels and suggests that the protein C level is the limiting factor in the rate of protein C activation in vivo.
Adolescent↗
Detection of factor V Leiden from a drop of blood by PCR-SSCP.
Recently, a point mutation in the coagulation Factor V gene (G to A in position 1691) has been identified which makes the mutant Factor V (called Factor V Leiden) resistant to activated protein C. This defect is a well established genetic risk factor in venous thrombosis. Because of the high prevalence of Factor V Leiden in normal population (2-7%), it would be reasonable to perform a rapid and simple method for screening the genetic abnormality in population at risk. We have developed a simple, reproducible, rapid and cheap procedure that, using PCR and SSCP, allows the identification of the mutation responsible for Factor V Leiden. Specificity of this method has been tested in 319 samples: 304 normal, 14 heterozygous and 1 homozygous for Factor V Leiden. This assay allows non-isotopic Factor V Leiden identification by using frozen whole blood in 3 h. All these features make this test adequate for routine screening of this mutation in a large number of samples.
Factor V↗
[Endometriosis of the small intestine as a cause of intestinal obstruction].
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Endometriosis↗
[Subcutaneous administration of desmopressin to plasma donors: a controlled study].
BACKGROUND: The aim of the present controlled study was to assess the effect of subcutaneous administration of desmopressin acetate (DDAVP) on the yield of Factor VIII (FVIII) and von Willebrand Factor (vWF) obtained in cryoprecipitates after plasmapheresis collection. SUBJECTS AND METHODS: Fifteen plasma donors underwent twice plasmapheresis collections using an "Autophereses C. model A-201" and cryoprecipitates were prepared using standard methods. In every subject of study one of the procedure was performed 35 min after subcutaneous administration of DDAVP (0.3 micrograms/kg), obtained from a highly concentrated preparation of the drug (40 micrograms/ml). Prior to the other apheresis procedure no chemicals were administered. Evaluation of FVIII and vWF levels was performed in peripheral blood samples obtained at different time points and cryoprecipitates product samples. RESULTS: Administration of DDAVP led to two-fold increase the yield of FVIII and vWF immediately before the performance of plasmapheresis. DDAVP stimulation resulted in an increase in the yield of FVIII and vWF in cryoprecipitates, compared with levels in the absence of the drug (703 +/- 53 and 768 +/- 51 U versus 227 +/- 12 and 362 +/- 20 U, respectively). No adverse effects but flushing were observed after DDAVP administration. CONCLUSIONS: Subcutaneous administration of DDAVP prior to plasma collection is a safe method to improve drastically the content of FVIII and vWF in cryoprecipitates. This procedure should be considered as an useful tool to help in providing self-sufficiency of plasma.
Adult↗
Activation of the protein C pathway in acute sepsis.
To obtain quantitative information on the in vivo activation of the protein C system during the acute phase of sepsis, several components of the protein C pathway were studied in 18 patients. Blood samples were obtained one day after diagnosis (day 1) and, in 11 patients, also on the fourth and tenth days after diagnosis (days 4 and 10). On day 1, patients showed laboratory signs of haemostatic alterations such as positive fibrinogen/fibrin degradation products, and increased thrombin:antithrombin-III (TAT) complex levels. Compared with the control group, patients on day 1 had significantly decreased (p < 0.001) antigenic protein C (69 +/- 28%) and protein C inhibitor (PCI) (33 +/- 22%) whereas a significant increase in the levels of activated protein C (APC) complexed with alpha 1-antitrypsin (alpha 1AT) (APC:alpha 1AT, 26 +/- 15 ng/mL) and APC:PCI complex (3.0 +/- 2.0 ng/mL), and in the level of plasma kallikrein (KK) complexes with PCI (KK:PCI) (31 +/- 22 ng/mL) was observed. There was a positive correlation between APC:alpha 1AT and TAT complex levels (r = 0.597, p = 0.009). In the follow-up a trend toward normal values in antigenic protein C and PCI, and in APC:PCI and KK:PCI complex levels was found. However, PCI remained significantly decreased compared to normal values. C4b-binding protein, alpha 1AT, and TAT and APC:alpha 1AT complexes did not show any significant variations during the course of the disease, suggesting the contribution of the inflammatory and haemostatic responses, in spite of the good recovery of the patients. This study shows that in the course of sepsis, patients experience a generalized activation of the protein C pathway which was more prominent on day 1, resulting in the consumption of protein C and PCI and in the increase of APC:inhibitor complexes. Moreover, these data provide further evidence that KK:PCI circulating complexes occur in vivo.
Acute Disease↗
[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↗
Effect of rhG-CSF on the mobilization of CD38 and HLA-DR subfractions of CD34+ peripheral blood progenitor cells.
Several studies have demonstrated that both CD34+/CD38- and CD34+/HLA-DR- human hematopoietic progenitor cells have properties associated with hematopoietic stem cells. However, the kinetics of these two cell populations in human peripheral blood (PB) after priming with granulocyte colony-stimulating factor (rhG-CSF) has not been investigated. By using flow-cytometric analysis we have shown that administration of rhG-CSF to 14 patients eligible for peripheral blood progenitor cell (PBPC) transplantation led to an increment of CD34+/CD38+ and CD34+/HLA-DR+ cells in the PB that paralleled the increase of total CD34+ cells, indicating that such subpopulations are responsible for the major release of CD34+ cells. Furthermore, rhG-CSF priming led to a significant mobilization of fractions of more immature CD34+/CD38- and CD34+/HLA-DR- cells to the PB. In the leukapheresis preparations, the average frequency of CD34+ cells lacking the CD38 or HLA-DR antigens was low (5% and 30%, respectively), with little overlap between the CD38- and HLA-DR- subpopulations. In addition, the yield of each subset of CD34+ cells (CD34+/CD38 +/- and CD34+/HLA-DR +/-) in the PB correlated with the numbers in the collected material. The results of the present study indicate that administration of rhG-CSF causes a significant increase of CD34+/CD38 +/- and CD34+/HLA-DR +/- cells in PB, and that such cells can be then safely harvested by leukapheresis procedures.
ADP-ribosyl Cyclase↗
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↗