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Biomedical subjects

M J Nieto

Publications and source records attributed to M J Nieto.

At least 19 recordsLinked to original sources
PubMed2005

Benzenesulfonamide analogs of fluoroquinolones. Antibacterial activity and QSAR studies.

The structure-activity relationships (SAR) of new antibacterial benzenesulfonamidefluoroquinolones (BSFQs), coming from derivatization of N4-piperazinyl of ciprofloxacin (CIP) were studied. The behavior of the new BSFQ series was similar to the previously norfloxacin (NOR) analogs reported, making possible a quantitative structure-activity relationships (QSAR) analysis of the complete set of BSFQs. The presence of the benzenesulfonylamido (BS) groups shifted the activity of classic antimicrobial fluoroquinolones from being more active against Gram-negative to Gram-positive strains. QSAR studies through Hansch analysis showed a linear correlation of the activity with electronic and steric parameters. Small electron-donor groups would increase the in vitro activity against Gram-positive bacteria. Hydrophobic properties played a minor role when activity is measured as minimum inhibitory concentration (MIC). QSAR analysis also reinforces previous biological findings about the presence of new interactions with target topoisomerases.

Anti-Bacterial Agents↗
PubMed2002

Hydroxamic acids as pharmacological agents.

A variety of hydroxamic acid derivatives have recently been touted for their potential use as inhibitors of hypertension, tumor growth, inflammation, infectious agents, asthma, arthritis, and more. Here we provide a comprehensive review of the basic medicinal chemistry and pharmacology of hydroxamic acid derivatives that have been examined as inhibitors of zinc metalloproteases, matrix metalloproteinases, leukotriene A(4) hydrolases, ureases, lipoxigenases, cyclooxygenases, as well as peptide deformilases.

Amidohydrolases↗
PubMed2000

The detection of contaminating clonal cells in apheresis products is related to response and outcome in multiple myeloma undergoing autologous peripheral blood stem cell transplantation.

In the present paper, we report on the use of the heteroduplex PCR technique to detect the presence of clonally rearranged VDJ segments of the heavy chain immunoglobulin gene (VDJH) in the apheresis products of patients with multiple myeloma (MM) undergoing autologous peripheral blood stem cell (APBSC) transplantation. Twenty-three out of 31 MM patients undergoing APBSC transplantation with VDJH segments clonally rearranged detected at diagnosis were included in the study. Samples of the apheresis products were PCR amplified using JH and VH (FRIII and FRII) consensus primers and subsequently analyzed with the heteroduplex technique, and compared with those obtained at diagnosis. 52% of cases yielded positive results (presence of clonally rearranged VDJH segments in at least one apheresis). The presence of positive results in the apheresis products was not related to any pretransplant characteristics with the exception of response status at transplant. Thus, while no one patient with positive apheresis products was in complete remission (CR), negative immunofixation, before the transplant, five cases (46%) with negative apheresis were already in CR at transplant (P = 0.01). The remaining six cases with heteroduplex PCR negative apheresis were in partial remission before transplant. Patients with clonally free products were more likely to obtain CR following transplant (64% vs 17%, P= 0.02) and a longer progression-free survival, (40 months in patients transplanted with polyclonal products vs 20 with monoclonal ones, P = 0.03). These results were consistent when the overall survival was considered, since it was better in those patients with negative apheresis than it was in those with positive (83% vs 36% at 5 years from diagnosis, P= 0.01). These findings indicate that the presence of clonality rearranged VDJH segments is related to the response and outcome in MM transplanted patients.

Hematopoietic Stem Cell Transplantation↗
PubMed1999

Clinical significance of CD34+ cell dose in long-term engraftment following autologous peripheral blood stem cell transplantation.

The number of CD34+ cells has been described as the best parameter for predicting the quality of engraftment in peripheral blood progenitor cell (PBPC) transplantation in the early post-transplant period. In this study we have determined the optimal number of CD34+cells in order to maintain engraftment in the long term in a series of 100 patients receiving autologous PBPC transplantation. Based on our previous experience on the speed of early hematopoietic recovery, four subgroups of patients were established: patients infused less than 0.75 x 106/kg CD34+ (n = 9), 0.75 to 1.25 (n = 24), 1.25 to 2.0 (n = 37) and more than 2.0 (n = 30). These groups were designated as low, intermediate-low, intermediate-high and high CD34 groups, respectively. Transitory loss of neutrophil engraftment was observed in 67%, 30%, 16% and 6% of patients in the four mentioned CD34 groups respectively, with statistically significant differences between the different groups. Significant differences were also observed between the low CD34 group and the rest of the groups as regards platelet and red blood cell transfusion requirements, fever episodes, days of hospitalization and antibiotic requirements throughout the first year. Our results show that the dose of CD34+ cells influences engraftment also in the late post-transplant period, and correlates with transfusion and antibiotic requirements, fever episodes and days of hospitalization during the first year post-transplant.

Anti-Bacterial Agents↗
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

Minimal number of circulating CD34+ cells to ensure successful leukapheresis and engraftment in autologous peripheral blood progenitor cell transplantation.

BACKGROUND: The number of peripheral blood (PB) CD34+ cells has been widely used to monitor the timing of leukapheresis for autologous transplantation. However, no cutoff value for CD34+ cells in PB has been defined as a guideline for the identification of patients in whom the harvest would be effective and those in whom there was a high probability of failure. STUDY DESIGN AND METHODS: The present study investigated the best threshold of CD34+ cells in PB for successful harvesting and engraftment, using 263 PB samples with their corresponding leukapheresis components. In addition, that measure has been compared to other commonly used criteria such as the white cell count, the number of mononuclear cells, and the number of colony-forming units-granulocyte macrophage in PB. RESULTS: Time to engraftment of both granulocytes and platelets was significantly influenced by the number of CD34+ cells transfused, but all patients receiving > or = 0.75 x 10(6) CD34+ cells per kg achieved engraftment within a reasonable number of days (> 0.5 x 10(9)/L granulocytes by Day 11 and > 20 x 10(9)/L platelets by Day 13). A clear correlation between the number of CD34+ cells per microL in PB and of CD34+ cells per kg collected was found at each apheresis (r = 0.9, p < 0.0001). Moreover, the number of CD34+ cells per microL measured in PB the day the first leukapheresis was initiated displayed an excellent correlation with the total amount of CD34+ cells per kg finally collected (r = 0.81, p < 0.0001). On the basis of the regression curve obtained and the clinical engraftment results, it was found that the presence of > 5 CD34+ cells per microL in PB ensured a good yield from the harvest in 95 percent of patients and would avoid an unsuccessful harvest in 81 percent of cases. CONCLUSION: A dose of only 0.75 x 10(6) CD34+ cells per kg guarantees hematopoietic recovery within a reasonable number of days. To initiate a leukapheresis from which enough progenitor cells may confidently be obtained, a minimum of 5 CD34+ cells per microL in PB is required.

Antigens, CD34↗
PubMed1998

Randomized study of filgrastim versus molgramostim after peripheral stem cell transplant in breast cancer.

BACKGROUND AND OBJECTIVE: The aim of this study was to compare the efficacy and toxicity of Filgrastrim (granulocyte colony-stimulating factor-G-CSF) versus molgramostim (granulomonocyte colony-stimulating factor-GM-CSF) after autologous peripheral blood stem cell transplant (PBSCT) in patients with breast cancer. To the best of our knowledge no randomized studies comparing filgrastrim and molgramostim have been published. DESIGN AND METHODS: Forty-two patients with breast cancer were randomized to receive filgrastrim versus molgramostim subcutaneous at a dose of 5 mcgr/kg starting on day 6 after PBSCT. PBSC were collected in all patients after stimulation with filgrastrim and infused following conditioning with cyclophosphamide, cisplatin and carmustine (n = 25) or cyclophosphamide, carboplatin and thiotepa (n = 17). RESULTS: The median days to reach > 0.5 x 10(9)/L granulocytes was similar for patients receiving filgrastrim (10.5 +/- 0.8 days) and molgramostim (10.2 +/- 0.9 days). No significant differences were observed in time taken to reach 20 x 10(9)/L platelets 10.8 +/- 2.2 vs 12 +/- 2.9 for filgrastrim and molgramostim, respectively, but in time to reach 50 x 10(9)/L was slightly lower in the filgrastrim arm (15.1 +/- 2.9 vs 18.9 +/- 8.4, p = 0.03). Nevertheless there were no differences in the number of platelets transfused. Time of discharge was two days earlier in the filgrastrim arm (15 +/- 4.2 vs 17.4 +/- 4.7, p = 0.04). Finally, the incidence of adverse side effects attributable to the cytokines (filgrastrim or molgramostim) was equivalent and only present in 19% of the patients. INTERPRETATION AND CONCLUSIONS: This randomized study shows that filgrastrim and molgramostim yield quite similar toxicity and efficacy for early hematopoietic reconstitution after PBSCT in breast cancer patients.

Administration, Cutaneous↗
PubMed1996

A randomized study comparing the effect of GM-CSF and G-CSF on immune reconstitution after autologous bone marrow transplantation.

Haemopoietic growth factors (HGFs) have been shown to accelerate recovery from severe neutropenia after autologous bone marrow transplantation (ABMT) but their effect on immune reconstitution is not well defined. The present study compares, through randomized trial, the in vivo effect of GM-CSF and G-CSF administration on the immune recovery of patients who underwent ABMT. For that purpose, we have sequentially analysed 14 different T, B and NK lymphoid cell subsets using appropriate dual staining during the first year following transplant (days +6, +17, +31, +66, +90, +120, +180, +360). 24 patients with lymphoproliferative disorders (20 lymphomas and four multiple myelomas) and who had undergone ABMT were included in the study. The median age was 43 years (range 22-62 years). All lymphoma patients were homogenously conditioned with BEAM. Our results show that both GM-CSF and G-CSF aid T-cell (CD3+/alpha beta) recovery though their contribution varies depending on the T-cell subset analysed. G-CSF contributed to a significantly faster recovery of CD8+ cells (P = 0.03). The CD8+ cell regeneration was produced mainly by activated cells (CD38+/HLA-DR+) which lacked the CD11b antigen. In contrast, GM-CSF favoured the regeneration of CD4+ cells (through both the CD45RO+ and CD45RA+ subset), leading to a higher CD4+:CD8+ ratio (P = 0.007). No statistically significant differences were detected in the three groups of patients as regards both the recovery of NK cells and NK activity. Furthermore, the use of HGF did not seem to exert a significant influence on the recovery of B lymphocytes. This recovery was based on the CD5+ subpopulation that showed a rapid rise after the first month. We suggest that G-CSF and GM-CSF not only influence myeloid recovery, but also regeneration of the immune system after ABMT.

Adult↗
PubMed1996

[Effect of chemotherapy on hematopoietic stem cells in peripheral blood].

PURPOSE: To analyze the effect of conventional chemotherapy on haematopoietic progenitor cells (HPC) from peripheral blood (PB). PATIENTS AND METHODS: The present work studies the behaviour of CFU-GM from PB in 47 patients subjected to conventional chemotherapy with the following diagnoses: non-Hodgkin's lymphoma (NHL): 16; Hodgkin's disease (HD): 8; multiple myeloma (MM): 5; acute leukaemia (AL): 8; solid tumor (ST): 10. A total of 57 studies was performed. As controls, 51 samples of PB from healthy subjects were used. Cultures were made in semisolid medium (methylcellulose), using PHA-LCM as stimulant, evaluating the growth of clusters (cl) and colonies (col) on days 7 and 14. RESULTS: Our findings show that in the overall series of patients the number of clusters from days 7 and 14 and of colonies-7--that is the most differentiated progenitor cells--were decreased with respect to the controls while colonies-14 were slightly increased. When the patients were separated by diagnostic groups, the col-14 were found to be increased in ST (p = 0.03) and in AL; in NHL col-14 were the same as in the controls. In the patients with HD all progenitor cells, including col-14 were much lower than the control values (p = 0.005). In order to determine whether the kind or the amount of chemotherapy received might affect these progenitor cells, we have analyzed the cases of NHL, 11 patients treated with moderate chemotherapy versus 12 patients receiving intensive chemotherapy: a stronger degree of growth in the latter, although with no significant differences. On comparing the cases that had received little previous chemotherapy (< 5 courses) against those who had received more than 5 courses growth was seen to be stronger in the patients who had received the fewest courses (p = 0.04). CONCLUSIONS: These results indicate that the HPC from PB are scanty in certain diseases, such as HD and that in all lymphomas the collection of these cells for transplantation purposes should be performed before they have damaged by an excessive number of chemotherapy courses.

Acute Disease↗
PubMed1995

[Influence of hematopoietic growth factors on transfusion support following autologous bone marrow transplantation].

PURPOSE: To determine the effect of haematopoietic growth factors (HGFs) (G-CSF and GM-CSF) on supporting platelet and red blood cell (RBC) transfusions in patients undergoing autologous bone marrow transplantation. PATIENTS AND METHODS: We retrospectively evaluated the transfusion requirements of 44 patients over three months post-transplant. Ten of these patients received recombinant human G-CSF and ten received GM-CSF. This group was compared with the control group, formed of 24 patients who did not received HGFs. The patients receiving HGFs did not differ significantly from those who did not receive growth factor with regard to age, sex, diagnosis, number of bone marrow cells infused and clinical factors affecting the efficacy of platelet and/or RBC transfusion (fever, infection, amphotericin B treatment, bleeding episodes). Statistical analysis of the results was made using the Mann-Whitney U test, with a p value significant at the 0.05 level. RESULTS: No significant effect of HGFs on platelet cell recovery was observed, but there was a trend for the time taken to recovery to increase. The median time of duration of platelet support dependence in the HGFs treated group was 19 days (range 7-100), compared with 15 days (range 3-65) in the control group. The number of platelet transfusions was 8.5 (2-43) and 7.5 (1-33) respectively. The treated patients received a median of 57 units of platelets (range 12-363), compared with 49 in the controls (range 7-206). In NHL there was a reduced need for platelet transfusions in HGFs group. In HD, HGFs increased platelet usage considerably (p < 0.05), although these groups were formed by only 5 and 7 patients respectively. The median RBC usage was the same between both patient groups (6 units of packed red cells). CONCLUSION: In our patients, the administration of HGFs has no beneficial effect on blood product requirements.

Adolescent↗
PubMed1994

[Clonogenic cells of acute leukemia secondary to myeloproliferative and myelodysplastic syndromes].

PURPOSE: To assess if the in vitro behaviour of leukaemic colony-forming units (CFU-L) from secondary leukaemias is similar to that of the de novo acute myeloblastic leukaemia. An attempt was also made to verify if such behaviour correlated with the characteristics of the disease or with the cell-surface markers of the leukaemic population. PATIENTS AND METHODS: The study was carried out on 21 patients with secondary acute leukaemia (12 had previous myelodysplastic syndrome, MDS-AL, and 9 had previous chronic myeloproliferative syndromes, MPS-AL). Peripheral blood mononucleated cells were cultured on methyl-cellulose with MCL-PHA stimulation. The dishes were examined after 7 days of incubation in humid 37 degrees C environment with 5% CO2. Direct or indirect immunofluorescence was used for the immunophenotypic analysis and the patients were divided in two groups: 1) immature phenotype, which include those cases expressing only precursor (CD34) or pan-myeloid (CD33/13) antigens, and (2) mature phenotype, comprising the caes with granulomonocytic (CD15, CD14), erythroid (glycophorin) or megakaryocytic (CD61) differentiation. The statistical analysis was done with the BMDP programme. RESULTS: Up to 95% of the secondary acute leukaemias proliferate in vitro, as opposed to 82% of the de novo ones, the difference not being significant (p = 0.14). Successful cell showing was clearly superior in the former (p = 0.02), mostly due to higher proliferation of the MPS-AL cells. Neither the clinico-biologic characteristics of the patients nor the phenotype of the blast cells correlated with the in vitro behaviour of CFU-L. Only CD19 antigen expression and nuclear TdT provided a lesser in vitro growth (p = 0.05 and p-0.06, respectively). CONCLUSION: In general terms, secondary leukaemias, especially MPS-AL, show higher in vitro growth than de novo acute myeloblastic leukaemias.

Adult↗
PubMed1992

Concomitant chronic lymphocytic leukemia (CLL) and acute myeloid leukemia. Complete remission of CLL achieved with high-dose cytosine arabinoside.

The concomitant presentation of acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) is rare with so far only eleven cases reported. In addition, the achievement of complete remission (CR) in CLL is exceptional and generally not assessed by immunophenotypical investigations. We report a case with a simultaneous occurrence of AML and CLL in which, in addition to the complete remission of AML, an eradication of the CLL clone was obtained following high-dose cytosine arabinoside. The immunophenotypic investigation of minimal residual disease showed that less than 1 x 10(-3) CD19+/CD5+ B-cells remained in bone marrow.

Acute Disease↗
PubMed1989

[Study of leukemic colony-forming units (CFU-L) in non-lymphoblastic malignant hemopathies].

CFU-L is considered as the clonogenic cell of acute non-lymphoblastic leukaemias (ANLL). Twenty-five malignant myelogenous hemopathies (5 blast crisis and 20 "de novo" ANLL) were studied in order to assess the proliferative capability of these cells and its relationship to FAB types and the achievement or not of complete remission (CR). The proliferative capability was assessed by culture on methylcellulose using conditioned leucocyte medium stimulated with phytohaemagglutinin as stimulating agent. Cell proliferation was observed in 21 cases, reaching 100% of the blast crisis and 80% (i.e., 16 cases) of the "de novo" ANLL. As regards the FAB types, it was found that the leukaemias with monocytic cells showed higher cell-growth than those of granulocytic lineage (90%, vs 60%). Of the patients not achieving CR (12 cases) colonies were formed in 66.6% (8 cases), while of the 8 patients who attained CR only in 3 (37.5%) were colonies observed. It was concluded that the FAB types of ANLL show different proliferative capability, which might influence the prognosis of the disease.

Blast Crisis↗
PubMed1987

Determination of the thermodynamic ionization constants of cefroxadine.

The values of the thermodynamic ionization constants of the carboxylic (pK = 3.30 +/- 0.02) and amine (pK = 7.00 +/- 0.06) groups of cefroxadine were determined at 35.0 degrees C using potentiometric data. The apparent ionization constants of these groups were also determined at 35.0 degrees C, and at different values of ionic strength.

Cephalosporins↗