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Biomedical subjects

L Vázquez

Publications and source records attributed to L Vázquez.

At least 19 recordsLinked to original sources
PubMed1999

Interferon alpha for chronic myeloid leukemia relapsing after allogeneic bone marrow transplantation.

Interferon alpha (IFN alpha) induces cytogenetic responses in patients with chronic myeloid leukemia (CML) who relapse after allogeneic bone marrow transplantation (BMT). The purpose of this study was to analyze the therapeutic role of IFN alpha in this setting. The experience of a single institution and the published results on this topic were evaluated. We have included patients who received IFN alpha as a single agent, excluding those patients who received previous or simultaneous donor leukocyte infusions. The outcomes of 11 patients treated in our center and those of 108 previously reported patients have been analyzed. Five out of 11 patients treated in our institution obtained a complete cytogenetic response (CGR). Two patients continue in complete cytogenetic response 3.5 and 8.2 years later, and the qualitative RT-PCR is negative for bcr-abl RNA. The CGR has been transient in one patient, and follow-up is short in the other two. Secondary effects have been acceptable, with myelosuppression as the main toxic effect. Graft-versus-host disease did not occur. The literature review identified 108 patients treated with IFN alpha as sole therapy for relapsed CML. Cytogenetic response and CGR seem to be better in patients with cytogenetic relapse, as compared to patients with hematologic relapse (61% vs. 45% and 45% vs. 28%, respectively). Several patients remained in CGR for more than 5 years. This overview also suggests that CGR is more frequent when IFN alpha is used in patients relapsing after non T-depleted BMT. IFN alpha induces complete cytogenetic response in nearly half of the patients with CML who relapse after allogeneic BMT, with acceptable toxicity. We believe that these results using IFN alpha as a front-line therapy for CML relapsing after BMT warrant a randomized comparison with donor lymphocyte infusions.

Antineoplastic Agents↗
PubMed1999

Detection of abnormalities in B-cell differentiation pattern is a useful tool to predict relapse in precursor-B-ALL.

Immunophenotypic investigation of minimal residual disease (MRD) has traditionally been based on the investigation of phenotypic aberrants at diagnosis to be used later as a target for MRD detection. This approach has several shortcomings (it is only applicable to patients with aberrant phenotypes, requires a diagnostic sample, and is patient-specific) and therefore a search for simpler alternatives is warranted. The present study is based on the hypothesis that in precursor-B-ALL patients the persistence of residual leukaemic cells may induce abnormalities in the precursor-B-cell compartment in bone marrow (BM) and these could be used as a criteria to predict relapse. These abnormalities may include: (1) the presence of an increase in the frequencies of immature B cells (CD34+/CD19+ or CD20-/CD19+) or (2) the existence of an altered B-cell differentiation pathway due to a blockade or to the presence of B cells outside the normal pathway. A total of 180 BM samples from 45 consecutive precursor-B-ALL patients who achieved morphological complete remission (CR) were analysed by multiparametric flow cytometry. Our results show that a significant increase in immature B-cell subsets or an altered B-cell differentiation predicts a high relapse rate (P<0.01) and a shorter disease-free survival (P<0.01). Moreover, abnormalities in either of these two criteria detected at specific time points during follow-up (end of induction, maintenance, or after treatment) were associated with a significantly shorter disease-free survival (P<0.01). In summary, the investigation of abnormalities in B-cell differentiation is a relatively simple and cheap approach for predicting relapse in precursor-B-ALL patients.

Adolescent↗
PubMed1999

Randomized prospective study comparing cost-effectiveness of teicoplanin and vancomycin as second-line empiric therapy for infection in neutropenic patients.

BACKGROUND AND OBJECTIVE: The current health-care philosophy dictates that new therapies should always be evaluated for their economic impact. Along with acquisition cost, the cost of delivery, monitoring, adverse effects and treatment failure must also be considered when determining the total cost of therapy. These auxiliary costs can be significant and greatly alter the overall cost of a drug treatment. We conducted a prospective randomized study to evaluate the efficacy, safety and cost of vancomycin and teicoplanin therapy in patients with neutropenia, after the failure of empirical treatment with a combination of piperacillin/tazobactam and amikacin. DESIGN AND METHODS: Seventy-six febrile episodes from 66 patients with hematologic malignancies under treatment, neutropenia (neutrophils <500/mm3) and fever (38 degrees C twice or 38.5 degrees C once) resistant to the combination piperacillin/tazobactam and amikacin were included in the study. RESULTS: Primary success of second-line therapy was obtained in 35 cases (46%) with no significant difference between vancomycin (17/38) and teicoplanin arms (18/38). No difference in renal or hepatic toxicity related to the antibiotic therapy was observed. The average cost per patient according to glycopeptide used was $450+/-180 for the teicoplanin group and $473+/-347 for the vancomycin group. Interestingly, in the teicoplanin arm, drug acquisition accounted for 97% of the total cost, while in the vancomycin arm administration and monitoring play an important role in overall costs. INTERPRETATION AND CONCLUSIONS: In conclusion, our pharmacoeconomic analysis demonstrates that teicoplanin and vancomycin can be administered in neutropenic hematologic patients with similar efficacy and direct costs.

Amikacin↗
PubMed1998

[Immune reconstitution after autologous progenitor hemopoietic cell transplantation. A study comparing autologous bone marrow and autologous peripheral blood transplantation].

BACKGROUND: In order to find out the effect of peripheral blood (PB) hematopoietic progenitor cells on immune reconstitution the present study compares, through a randomized trial, some lymphoid subsets after peripheral blood (PBT) or bone marrow (BMT) autologous transplantation. MATERIAL AND METHODS: Twelve patients suffering from malignant hematological disorders were included (6 BMT and 6 PBT). From these patients 14 lymphoid and natural killer (NK) subsets were sequentially analyzed using appropriate dual staining. NK activity was analyzed by measuring Cr51 release from the K562 cell line. Studies were done in days and -6, +10, +17, +24, +31, +38, +52, +66, +90, +120, +180 and +360 after transplantation. RESULTS: The CD8+ cell regeneration was produced mainly by activated cells (CD38+), and no differences were observed between BMT and PBT, but CD8+ HLADR+ cells were higher in the PBT group. During the first year after transplantation CD4+ lymphoid cells were never within normal range, and its recovery was due to the memory subset (CD4+/CD45RO+). The CD19+ lymphocytes began their regeneration after the first month and it was produced mainly by by the CD19+/CD5+ subset. NK cells recovered faster in patients who underwent PBT, but NK activity was similar in both subgroups of patients and it was within normal range from day +17 until the end of the study. CONCLUSION: T, B and NK lymphoid reconstitution do not differ significantly between patients that receive BM or PB as hemathopoietic rescue, but PB seems influence a faster reconstitution of cytotoxic subsets (CD8+/HLADR+ and NK lymphoid cells).

Adolescent↗
PubMed1998

Isolation of the receptor for Amaranthus leucocarpus lectin from murine peritoneal macrophages.

The receptor for Amaranthus leucocarpus lectin from CD-1 resident macrophages was purified with affinity chromatography with biotin labeled A. leucocarpus lectin and using avidin-agarose as affinity matrix. The receptor is a glycoprotein of 70 kDa that contains 18% of sugar by weight; it is mainly composed of galactose and N-acetyl-D-galactosamine in its saccharidic portion, and lacks sialic acid; the protein is rich in glycine, serine and alanine and lacks cysteine residues. The amino terminus of the receptor is blocked. By ionic strength chromatography on a mono P column in anionic form we purified three isoforms from the affinity purified receptor, each showing quantitative differences in glycosylation. The A. leucocarpus lectin receptor is identified only in resting, not activated, macrophages suggesting that it plays a role in activation mechanisms of macrophages.

Animals↗
PubMed1998

Autologous stem cell transplantation (ASCT) for poor prognostic Hodgkin's disease (HD): comparative results with two CBV regimens and importance of disease status at transplant.

Clinical outcome of 47 consecutive patients with advanced HD who underwent ASCT in our Department was analyzed retrospectively. Median age was 28 years (28 males and 19 females). At transplant, 15 (32%) patients were in CR (five in first CR after two chemotherapy regimens and 10 in second CR), eight (17%) in PR (seven without a prior CR), 22 (51%) had relapsing disease (19 with sensitive relapse) and two had primary refractory disease. The CVB regimen with two different schedules was used: 22 (47%) patients received standard CBV (CY 6 g/m2, BCNU 300 mg/m2 and etoposide 600 mg/m2) and 25 (53%) received an increased CBV dose (CY 7.2 g/m2, BCNU 440 mg/m2 and etoposide 2 g/m2). Antitumor response for 28 evaluable patients was similar for both CBV regimens: 87 and 75% (P=0.39). At 7.2 years, actuarial overall survival (OS), progression-free survival (PFS) and event-free survival (EFS) for the whole series were 51.7+/-8%, 34+/-9% and 28+/-8%, with a median follow-up for the surviving patients of 3 years (0.7-7.6). No differences in these survival functions according to the CBV regimen used were observed (P=0.57). A history of a prior CR (P=0.003), duration of first CR >1 year (P=0.04), absence of bulky nodal disease at transplant (P=0.054), absence of extranodal disease at transplant (P=0.01), and a CR status at transplant (P=0.0006) were associated with a better PFS on univariant analysis. On multivariate analysis, only CR status at transplant remained significant (P=0.05). When patients in second CR at transplant and those in first sensitive relapse were analyzed separately, no differences in clinical characteristics or in treatment received pretransplant were observed; however, PFS was significantly different (P=0.01). In conclusion, CR status at transplant is useful in identifying 'good risk' patients and is necessary to obtain the greatest benefit from ASCT independent of the CBV regimen used.

Adolescent↗
PubMed1998

[Treatment with lymphoblastoid alpha interferon in patients with chronic myeloid leukemia refractory to recombinant interferon alpha 2].

The results of the treatment with lymphoblastoid alpha interferon (IFN-alpha N1) in 10 patients with chronic myeloid leukaemia who had poor response to previous recombinant alpha interferon (rIFN-alpha) are presented. Eight of these patients had not developed anti-alpha 2 interferon antibodies, and 2 had non-neutralising anti-IFN antibodies. Three of the 10 patients received benefit from IFN-alpha N1 treatment. Two of them, with no response to rIFN alpha 2, attained complete haematologic response wit IFN-alpha N1. Cytogenetic responses although minimal, were achieved as well. The third patient, after receiving rIFN-alpha for 3 years with no response, had partial cytogenetic response after 4 months of treatment with IFN-alpha N1. These results suggest that IFN-alpha N1 when used in patients refractory to IFN-alpha N1. These results suggest that IFN-alpha N1 when used in patients refractory to IFN alpha 2 without anti-IFn alpha 2 neutralising antibodies may be useful in a minority of patients, although the frequency of cytogenetic responses is low.

Adult↗
PubMed1997

Participation of a sialic acid-specific lectin from freshwater prawn Macrobrachium rosenbergii hemocytes in the recognition of non-self cells.

Phagocytic activity of circulating hemocytes from freshwater prawns is mediated by a small group of granulocytes. Recognition of nonself cells by these cells seems to be mediated by two independent mechanisms: specific, via O-acetylsialic acid, as well as N-acetylated sugars on recognized cells and a nonspecific one. Both mechanisms show differences in their optimal temperature and time differences for activity. Hemocytes with phagocytic activity interact positively with rabbit IgG raised against the serum lectin. Attempts to elucidate the nature of the membrane-lectin on hemocytes performed by electroimmunotransfer blot assays on cell lysates indicates the presence of two major proteins with a molecular weight of 68-72 kDa. Electron microscopy revealed a regular distribution of lectin on hemocyte plasma membranes. Our results suggest the active participation of a membrane lectin in the recognition of nonself.

Animals↗
PubMed1997

Sequential intravenous-oral ciprofloxacin plus amoxycillin/clavulanic acid shortens hospital stay in infected non severe neutropenic patients.

The objective of this study was to determine the efficacy and safety of the combination ciprofloxacin plus amoxicillin/clavulanic acid as an empirical treatment of infection in hematologic patients without severe neutropenia. These drugs allowed us to carry out a sequential therapy, first intravenously and later orally, so that the patient could be discharged as soon as there was a response. Serum concentrations of ciprofloxacin were monitored in this study. Forty seven of the sixty-six patients included (71%) responded to the treatment with no differences between the dosages of ciprofloxacin employed (600-900 mg daily in two or three divided doses). In the patients who responded, the signs and symptoms of infection lasted only three days, which could allow a short hospital stay (median of six days). In the first pre and post-dose serum samples, ciprofloxacin concentrations were significantly higher when the drug was administered every 8 h. Nevertheless, 72 h after the beginning of treatment, they had leveled out in either 8 and 12 h schemes. The toxicity of the treatment was very light, with only four cases with adverse effects, grades I and II. This data suggests that the employed combination is effective and safe and can considerably decrease costs incurred through the admission of hematologic patients with serious infections but without severe neutropenia.

Administration, Oral↗
PubMed1997

BEAM chemotherapy followed by autologous stem cell support in lymphoma patients: analysis of efficacy, toxicity and prognostic factors.

In the present paper, we evaluate tolerability, outcome and prognostic factors in patients with poor prognosis non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) when uniformly treated with BCNU, etoposide, cytarabine and melphalan (BEAM) and autologous stem cell transplant (ASCT). On hundred and forty-eight patients with NHL (n = 112) or HD (n = 36) received BEAM followed by infusion of bone marrow (n = 55), peripheral blood stem cells (n = 79) or both (n = 14). Twenty-eight patients had low-grade lymphoma (LGL), 68 intermediate- and 16 high-grade lymphoma (IGL). Within the NHL group, 21 patients were in 2nd or subsequent complete remission (CR) at transplant, 34 had sensitive disease and 11 resistant disease; 46 patients were transplanted in 1st CR due to the presence of > or = 2 adverse prognostic features at diagnosis or to a slow CR. Of the HD patients at transplant 17 had active disease, 16 were in > or = 2 CR and three in 1st CR. The overall percentage of toxic deaths was 5.4%, while in the group of patients transplanted with PBSC it was only 1.3%. NHL patients: 78% were in CR following ASCT, including 25 out of 45 patients (56%) who were transplanted with active disease. Only two of the 11 patients transplanted with resistant disease achieved CR. Incidence of overall survival (OS) and disease-free survival (DFS) at 3 years was 65 and 75%, respectively. As far as histology was concerned, OS was significantly better for patients with LGL in comparison with IGL (88 vs 56%) (P = 0.002). DFS was significantly higher for patients transplanted in first CR or first partial remission (PR) than it was for those transplanted in a later CR or PR (86 vs 53%) (P = 0.02). Multivariate analysis for OS showed that histology, bulky disease, poor performance status at transplant and achievement of CR were independent prognostic factors. In addition, a high number of infused MNC was associated with poor DFS. HD patients: 30 (83%) were in CR after transplantation, with 25 maintaining CR at the end of the study. Only one of the four patients transplanted with resistant disease reached CR. Incidence of OS and DFS at 3 years was 78 and 81%. DFS was similar for patients transplanted with early or late relapse (95 and 93%). With multivariate analysis, the only independent variable for OS was CR after transplant. In conclusion, the present results demonstrate the efficacy and low toxicity of the BEAM regimen in high-risk lymphoma patients with sensitive disease. Other strategies should be investigated for patients with refractory lymphoma.

Adolescent↗
PubMed1997

On the correct determination of reference values for serum antibodies against pigeon serum antigen using a group of healthy blood donors.

An enzymatic immunoassay was developed in order to evaluate the statistical distribution of IgG serum antibodies against pooled pigeon sera antigen in 102 healthy blood donors (HBD). A non-normal distribution was obtained as demonstrated by abnormal values of skewness (2.02) and kurtosis (6.50). A cut-off point (0.120) was determined from the mean plus 2 standard deviations of the optical density values obtained in the HBD group. This value was able to segregate 94% of subjects. However, when calculation of the mean less 2 SD was performed to delimit 95% of the samples, an aberrant negative value was obtained. In contrast, when the nonparametric method of percentile calculation was applied, an optical density value of 0.130 discriminated 97.5% of samples. In addition, the interval between p97.5 and p2.5 delimited 95% of samples. We conclude that when reference values and cut-off point are determined from an enzymatic immunoassay, careful analysis of the statistical distribution of reference values is necessary in order to avoid the inappropriate application of parametric procedures as demonstrated in this study for antibodies against pigeon serum antigens.

Adult↗
PubMed1996

Analytical applications of retinoid-cyclodextrin inclusion complexes. 1. Characterization of a retinal-beta-cyclodextrin complex.

In studies in these laboratories on the supramolecular chemistry of the retinoids, it has been recently confirmed that inclusion of these substances within the cavity of cyclodextrins protects their excited states, thus improving their photochemical stability. In the present paper, the isolation is described of a crystalline stable complex between retinal and beta-cyclodextrin, which has been characterized by means of several techniques including atomic force microscopy (AFM). The complex shows distinct spectroscopic differences from both retinal and beta-cyclodextrin. Thus, it absorbs at lambda(max) = 380 nm in water whereas retinal is insoluble; it shows room-temperature luminescence, which retinal does not; finally, it give 1H-NMR and 13C-NMR spectra in d6-DMSO with clear differences in chemical shifts with respect to those of beta-cyclodextrin. Besides these studies in solution, the behaviour of the complex in the solid state has been compared with that of physical mixtures of retinal and beta-cyclodextrin. IR spectroscopy shows clear differences, particularly a shift in the retinal carbonyl absorption (1644-1672 cm-1). AFM studies reveal the existence of aggregates; X-ray diffractometry also supports the formation of a cyclodextrin-retinal complex.

Cyclodextrins↗
PubMed1996

Differentiating inclusion complexes from host molecules by tapping-mode atomic force microscopy.

Tapping-mode atomic force microscopy imaging under different cantilever vibration amplitudes has been used to differentiate the host beta-cyclodextrin nanotubes from retinal/beta-cyclodextrin inclusion complex nanotubes. It was observed that both compounds were deformed differently by the applied probe force because of their different local rigidity. This change in the elasticity properties can be explained as a consequence of the inclusion process. This method shows that tapping-mode atomic force microscopy is an useful tool to map soft sample elasticity properties and to distinguish inclusion complexes from their host molecules on the basis of their different mechanical response.

Biophysical Phenomena↗
PubMed1995

[Allogeneic bone marrow transplantation in chronic myeloid leukemia. The clinical results and risk factors in 70 patients].

BACKGROUND: The 10 year experience of a single center performing allogeneic bone marrow transplantation in 70 patients with chronic myeloid leukemia (CML) is analyzed. METHODS: Seventy patients transplanted for CML between November 1982 and October 1992 were evaluated. Fifty-two patients were in the first chronic phase (FC), 10 in an accelerated phase, 4 in blast crisis and 4 in the second chronic phase. The combination of cyclosporin and methotrexate was the most commonly used prophylactic schedule for graft versus host disease (GVHD) (60 cases) and T depletion was not performed in any case. The combination of cyclophosphamide (120 mg/kg) and total body irradiation was used in 48 patients with the remaining patients received busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg). The estimation of survival was performed using the Kaplan-Meier limit product method. The prognostic factors influencing survival, disease free period and relapse were evaluated by Cox multivariate models of proportional risk. RESULTS: Actuarial survival at four years was 40% (95% Cl: 26-58%). Multivariate analysis selected variables associated with lower survival, the presence of acute GVHD (relative risk-RR-4.75), advanced disease phase (RR: 3.26) and age over 30 years (RR: 3.57). Eleven patients had relapsed. Multivariate analysis found the absence of chronic GVHD (RR: 5.3) and advanced phase (RR: 1.91) to be associated to a higher probability of relapse. In a separate analysis of the 48 patients transplanted in chronic phase who received cyclosporin and methotrexate, the disease free survival was longer for those under the age of 30 years (71.4% vs. 36%) without acute GVHD (68.8% vs. 39.6%) and those transplanted from a male donor (64.6% vs. 30%). CONCLUSIONS: Advanced phase of the disease, the presence of acute graft versus host disease and the age and female sex of the donor are the main factors associated to shorter survival in allogeneic bone marrow transplant for chronic myeloid leukemia. In contrast, the presence of chronic graft versus host disease decreases the possibilities of relapse.

Adolescent↗
PubMed1995

Specificity of the isolectins from the plant cactus Machaerocereus eruca for oligosaccharides from porcine stomach mucin.

Sugar specificity of the Machaerocereus eruca isolectins, MeAI and MeAII, has been determined by comparing the capacity of glycans with well defined structures to inhibit their haemagglutinating activity. Both are galactose-specific isolectins with high affinity for O-glycans. However, the two M. eruca isolectins recognize different oligosaccharidic sequences belonging to O-glycosidically linked glycans from porcine stomach mucin. The minimal structure recognized by MeAI on the porcine mucin glycans is the O-glycan core Gal beta 1,3GalNAc-ol, whereas MeAII has a more extended site and interacts with a biantennary O-glycan possessing the terminal trisaccharide Fuc alpha 1,2 (GalNAc alpha 1,3) Gal beta 1,4.

Animals↗