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Biomedical subjects

F Ortuño

Publications and source records attributed to F Ortuño.

At least 19 recordsLinked to original sources
PubMed2004

Serotonergic polymorphisms and psychotic disorders in populations from North Spain.

There is strong biological evidence relating alterations in the serotonergic system with mental disorders. These alterations may be originated at the DNA level by sequence mutations that alter the functioning of serotonin receptors and transporter. To test this hypothesis we investigated three genetic variants of the 5-HT2A receptor (-1438G/A, 102T/C and His452Tyr) and two variants of the serotonin transporter (a VNTR in the second intron and a 44 bp insertion/delition in the promoter region of the gene) in a clinical sample recruited in a human isolate and in surrounding areas in Northern Spain (N = 257) and in ethnically matched controls (N = 334). No clear association was found between 5-HT2A variants and psychosis. However, marginal associations were observed between the 5-HTT LPR and VNTR variants and psychosis (P < or = 0.05) indicating a minor contribution to psychosis of genetic alterations in this gene.

Adult↗
PubMed2002

Sustained attention in a counting task: normal performance and functional neuroanatomy.

We examined changes in relative cerebral flood flow (relCBF) using PET during a sustained attention paradigm which included auditory stimulation and different tasks of mental counting. Ten normal volunteers underwent PET (15O water) during a baseline state and under experimental conditions which included listening to clicks, serial counting with auditory stimulation, counting with no auditory stimulation, and an additional component of working memory and time estimation. All subjects performed within normal limits in a battery of neurocognitive tests, which included measures of attention and working memory. Both counting with auditory stimulation and counting with no auditory stimulation engaged motor cortex, putamen, cerebellum, and anterior cingulate. Furthermore, counting with no auditory stimulation relative to counting while listening resulted in significantly increased relCBF in the inferior parietal, dorsolateral prefrontal, and anterior cingulate. The findings obtained in this study support the notion that the parietal and dorsolateral prefrontal cortex are involved when time estimation and working memory are taking part in a task requiring sustained attention.

Acoustic Stimulation↗
PubMed2001

Differences in interleukins' patterns between dysthymia and major depression.

We assessed whether cytokine production-interleukin (IL)-1beta, IL-6 and tumour necrosis factor-alpha (TNFalpha)-is affected in depressed patients, dysthymia (Dt) and major depression (MD), and its association with various parameters of severity and clinical course. We found a possible different pattern of interleukin production between Dt and MD.

Adolescent↗
PubMed2001

Administration of post-autologous PBSCT rhG-CSF is associated with long-term low concentrations of bone marrow hematopoietic progenitor cells.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) has been widely used after autologous peripheral blood stem cell transplant (APBSCT) in an attempt to reduce the duration of neutropenia, but whether this treatment has any influence on long-term engraftment remains unknown. We have retrospectively analyzed data from breast cancer patients to compare post-APBSCT rhG-CSF administration in terms of the short-term benefit and myeloid marrow regeneration after 1 year. Group A included 10 patients not treated with post-APBSCT rhG-CSF, while groups B and C comprised 15 and 13 patients treated with this drug from days +1 and +6, respectively. No differences among the three groups were found in age, diagnosis, previous chemo-radiotherapy, CD34+/CD71- cell concentration in pre-transplant bone marrow (BM), mobilization schedule, CD34+ cell yield, conditioning regimen and post-transplant radiotherapy. Post-APBSCT rhG-CSF was shown to accelerate neutrophil recovery, but there were no significant differences in platelet recovery, transfusion requirements, days of fever, antibiotic administration or inhospital stay. With regard to BM hematopoietic precursors 1 year after APBSCT, significantly lower concentrations of total CD34+ cells, committed CD34+/CD33+ subsets, and more immature CD34+/CD71- cells were found in both groups B and C compared with patients not having received the cytokine (group A). Thus, post-APBSCT rhG-CSF administration does not appear to beneficially affect procedure outcome, and might even impair long-term marrow hematopoiesis.

Adult↗
PubMed2001

Identification of two subgroups of mantle cell leukemia with distinct clinical and biological features.

INTRODUCTION: Mantle cell leukemia (MCLeu) has been considered as a leukemic form of mantle cell lymphoma (MCL). However, the presence of certain features rarely observed in MCL, such as transformation to prolymphocytic leukemia (PLL) or indolent clinical course, suggests that MCLeu may represent a distinct disorder. METHODS: Seven cases of MCLeu with t(11;14)(q13;q32) and BCL1-IGH gene rearrangement were ascertained among 140 newly diagnosed chronic B-cell lymphoproliferative disorders with leukemic expression. Comparative genomic hybridization, FISH for specific gene loci, and immunological studies were preformed in them. RESULTS: In comparison with CLL, MCLeu cases had low immunological scores < or =2 with respect to B-CLL (P<0.0001). Expression of CD38 was absent in 43% of MCLeu and in 44% of B-CLL. Comparative genomic hybridization analysis identified genomic imbalances in 86% of MCLeu with a similar pattern than in MCL: gains of 3q, 8q involving MYC gene and 15q, and losses of 6q, 9p, 13q and 17p affecting P53 gene. Differently from MCL and CLL, genomic loss of 8p was frequently detected in MCLeu (83%). Although clinical presentation of MCLeu was indistinguishable from CLL, all patients but one had disease progression within three years. According to the immunologic and genomic profiles, two distinct subgroups of MCLeu were defined: one related to PLL, showing CD38-, deletion of P53, and MYC amplification and another which corresponds to a leukemic form of classical MCL, presenting with CD38+ and normal P53 and MYC status. CONCLUSION: MCLeu and MCL are closely related disorders, as they show similar genomic and molecular patterns. However, the deletion of the short arm of chromosome 8 may represent a specific marker for MCLeu. Two distinct subgroups of MCLeu may also be distinguished according to the immunologic and genomic cell profiles.

ADP-ribosyl Cyclase↗
PubMed2000

Mobilization of hematopoietic progenitor cells with paclitaxel (taxol) as a single chemotheraupetic agent, associated with rhG-CSF.

We assessed the mobilization capacity of taxol with rhG-CSF, both as a single chemotherapeutic agent and in the presence of cyclophosphamide (CY), and compared the effect with yields achieved when mobilization was performed solely with rhG-CSF. Fifteen patients with breast cancer received taxol 170 mg/m2 (continuous infusion, day 1) and rhG-CSF (8 microg/kg/day, from day 2 until the end of apheresis) (T-G group), while seven breast cancer patients were additionally treated with CY (4 g/m2) on day 2, followed by rhG-CSF starting at similar doses on day 3 (T-CY-G group). The PBSC collections after taxol with/without CY were compared with those of 30 breast cancer patients who had received rhG-CSF (8 microg/kg/day) for mobilization. No differences were found in the characteristics of patients included in any of the three mobilization groups. The median yield of CD34+ cells from all patients included in taxol containing schedules was 9 x 106/kg (range 2-26) collected with a median of one apheresis procedure (range 1-4). Leukaphereses began earlier in the T-G group (median day 8, range 7-10) than in the T-CY-G group (median day 13, range 11-17). In most patients (20 out of 22) who received taxol containing regimens, more than 2.5 x 106 CD34+ cells/kg, a threshold considered to be sufficient for hematopoietic reconstitution, were collected with a single apheresis. Those patients in the T-G group experienced less neutropenic and thrombocytopenic days, with all neutropenic fever episodes developing in patients treated with the T-CY-G schedule (43%). When considering priming with rhG-CSF alone in our historical cohort of 30 breast cancer patients, a significant detrimental effect was observed in comparison with taxol mobilizing schedules, in the number of aphereses performed, in the total yield CD34+cells and in the number of patients who achieved the target dose of 2.5 x 106/kg CD34+ cells within the first collection procedure. We conclude that taxol containing schedules are effective in mobilizing PBSC and facilitate the collection of high yields of CD34+ cells (usually more than 5 x 106/kg recipient body weight) with a reduced number of apheresis procedures. Taxol, as a single agent with rhG-CSF, exhibits less hematological toxicity than the combination chemotherapy mobilization regimen including CY. Bone Marrow Transplantation (2000) 25, 231-235.

Adult↗
PubMed2000

Re-mobilization of peripheral blood progenitor cells within a short time interval fails to achieve effective progenitor cell yields.

We report the case of a healthy donor who was mobilized for the purpose of performing an unrelated donor transplantation with subcutaneous injections of rhG-CSF. Because of accidental loss of progenitors, 3 days after completing the first collection, the donor was mobilized again with rhG-CSF, and progenitors were collected. While a similar increase in the pre-apheresis leukocyte count was observed in both procedures, fewer mononuclear cells were mobilized during the second rhG-CSF course, resulting in a poor CD34+ yield. These data suggest that an 8-day interval between commencement of rhG-CSF mobilizations is insufficient to predict an efficient collection of hematopoietic progenitors to ensure engraftment after bone marrow transplantation.

Female↗
PubMed2000

Sleep apnea and hypertension.

STUDY OBJECTIVES: To examine the central inspiratory drive response to hypoxia in patients with obstructive sleep apnea (OSA), according to their circadian BP profile, and in healthy control subjects. Another objective was to evaluate the relationships among sleep architecture, hypoxic sensitivity, urinary catecholamine excretion, and BP in OSA patients. PATIENTS AND INTERVENTIONS: Polysomnography, 24-h ambulatory BP recording, and urinary excretion of catecholamines were simultaneously examined in 24 consecutive OSA patients and 11 healthy subjects. OSA patients were categorized as being normotensive (type 1), having BP elevation only during sleep (type 2), and as being hypertensive with elevated BP at all times (type 3). The response of mouth occlusion pressure at 0.1 s after onset (P(0.1)) to progressive isocapnic hypoxic stimulation was measured. RESULTS: There was a significant difference in the P(0.1) response to hypoxia among control subjects ([mean +/- SD] 0.353 +/- 0.129 cm H(2)O/%) and type 1 (0.228 +/- 0.062 cm H(2)O/%), type 2 (0. 345 +/- 0.106 cm H(2)O/%), and type 3 (0.508 +/- 0.118 cm H(2)O/%) OSA patients. In OSA patients, chemosensitivity was related to the apnea-hypopnea index and to the nocturnal excretion of epinephrine. Significant relationships between the nocturnal excretion of epinephrine and BP were noted. On multiple linear regression analysis, the P(0.1) response to hypoxia was the only variable significantly related to diurnal (r(2) = 0.364; p = 0.005) and nocturnal mean BP (r(2) = 0.461; p = 0.002). CONCLUSION: The findings of the present study suggest a possible mediating role of the peripheral chemosensitivity in the association between sleep apnea and hypertension.

Adult↗
PubMed1999

Enumeration of CD4(+) T-cells in the peripheral blood of HIV-infected patients: an interlaboratory study of the FACSCount system.

The aim of the present study was to assess the interlaboratory reproducibility of the FACSCount system for the enumeration of peripheral blood (PB) CD4(+) T-cells. In each of the seven participating centers, both previously stained and unstained PB samples (n = 49) were received and either analyzed or stained and then analyzed. Interlaboratory reproducibility was checked in two different groups of centers (n = 3 and n = 4) where the study was performed in parallel. In addition, both the intralaboratory precision and accuracy of this system were analyzed in comparison with results obtained with conventional flow cytometry. Accordingly, upon comparing both methods, a high degree of correlation was observed in the total number of CD3(+) T-cells (coefficient of correlation of 0.9750 +/- 0.0184, slope of the best linear fit: 0. 9214 +/- 0.0311, y-intercept of 12 +/- 47) as well as in the number of CD3(+)/CD4(+) (coefficient of correlation of 0.9794 +/- 0.1457, slope of the best linear fit: 0.9463 +/- 0.0753, y-intercept of -11 +/- 36) and CD3(+)/CD8(+) (coefficient of correlation of 0.9728 +/- 0.0192, slope of the best linear fit: 0.9682 +/- 0.0735, y-intercept of 7 +/- 95) major subsets. In addition, low coefficients of variation (CV) were obtained for replicates, indicating the method's high degree of accuracy. The present study shows that with respect to the interlaboratory reproducibility reported for most techniques used for the enumeration of PB CD4(+) T-cells, the FACSCount system results in data with much lower coefficients of variance (CVs) (mean CV of less than 10%). Upon measuring the impact on results of different variables associated with either sample preparation or data acquisition and analysis, our study clearly shows that data acquisition and analysis does not influence the results by increasing variability since the coefficients of variation obtained for samples prepared in the same laboratory under the same conditions and read in different laboratories with different instruments were identical to those obtained for the replicates of the same samples read in each individual center. In contrast, interlaboratory variability, although low, significantly increased when sample preparation was carried out in different laboratories, suggesting that pipetting still represents the major source of variability in the FACSCount system.

CD4 Lymphocyte Count↗
PubMed1999

Autoaggression syndrome resembling acute graft-versus-host disease grade IV after autologous peripheral blood stem cell transplantation for breast cancer.

Acute graft-versus-host disease (aGVHD) after autologous progenitor cell transplantation has been associated with blood transfusion or cyclosporine. Mild aGVHD grades I-II, identified as autoaggression or engraftment syndrome, has recently been described in autologous progenitor transplantation. Here, we report the first case of pathologically documented grade IV aGVHD after autologous peripheral blood progenitor cell transplantation in a patient with breast cancer. The allogeneic origin was excluded by molecular techniques, and no cyclosporine or cytokines were administered.

Adult↗
PubMed1999

Role of the 807 C/T polymorphism of the alpha2 gene in platelet GP Ia collagen receptor expression and function--effect in thromboembolic diseases.

The variability of the platelet GP Ia/IIa density has been associated with the 807 C/T polymorphism (Phe 224) of the GP Ia gene in American Caucasian population. We have investigated the genotype and allelic frequencies of this polymorphism in Spanish Caucasians. The T allele was found in 35% of the 284 blood donors analyzed. We confirmed in 159 healthy subjects a significant association between the 807 C/T polymorphism and the platelet GP Ia density. The T allele correlated with high number of GP Ia molecules on platelet surface. In addition, we observed a similar association of this polymorphism with the expression of this protein in other blood cell types. The platelet responsiveness to collagen was determined by "in vitro" analysis of the platelet activation and aggregation response. We found no significant differences in these functional platelet parameters according to the 807 C/T genotype. Finally, results from 3 case/control studies involving 302 consecutive patients (101 with coronary heart disease, 104 with cerebrovascular disease and 97 with deep venous thrombosis) determined that the 807 C/T polymorphism of the GP Ia gene does not represent a risk factor for arterial or venous thrombosis.

Aged↗
PubMed1998

Bone marrow steady-state CD34+/CD71- cell content is a predictive value of rG-CSF-mobilized CD34+ cells.

Thirty-four patients diagnosed with breast cancer were included in a prospective study evaluating the bone marrow (BM) CD34+/CD71- cell content, as a predictive parameter of the CD34+ cell mobilization after rG-CSF administration. Analysis of the concentration of medullary CD34+/CD71- cells before priming schedules was significantly related with the collection of CD34+ cells in apheresis day 1 (P = 0.03, r = 0.36), apheresis day 1 + day 2 (P = 0.01, r = 0.42) or the total CD34+ cells collected (P = 0.005, r = 0.47). A BM CD34+/CD71- cell concentration greater than or less than a cut-off value of 30/microl was significantly associated with the yield of CD34+ cells collected by cytapheresis procedures (mean values 3.12 x 10(6)/kg, and 2.19 x 10(6)/kg, respectively, P = 0.013). These results suggest that in breast cancer patients undergoing priming with rG-CSF, steady-state BM CD34+/CD71- measurement is a relevant predictive parameter of CD34+ mobilization.

Adult↗
PubMed1997

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↗
PubMed1996

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↗