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Biomedical subjects

L Larrea

Publications and source records attributed to L Larrea.

At least 19 recordsLinked to original sources

Genetic analysis of the LGI/Epitempin gene family in sporadic and familial lateral temporal lobe epilepsy.

Mutations in the LGI1/Epitempin gene cause autosomal dominant lateral temporal lobe epilepsy (ADLTE), a partial epilepsy characterized by the presence of auditory seizures. However, not all the pedigrees with a phenotype consistent with ADLTE show mutations in LGI1/Epitempin, or evidence for linkage to the 10q24 locus. Other authors as well as ourselves have found an internal repeat (EPTP, pfam# PF03736) that allowed the identification of three other genes sharing a sequence and structural similarity with LGI1/Epitempin. In this work, we present the sequencing of these genes in a set of ADLTE families without mutations in both LGI1/Epitempin and sporadic cases. No analyzed polymorphisms modified susceptibility in either the familial or sporadic forms of this partial epilepsy.

Alleles↗

Comparison between two cord blood collection strategies.

BACKGROUND AND OBJECTIVES: Collection strategy is the first step for collecting good quality cord blood (CB) units. There are two principal different techniques to collect CB from the umbilical vein: in the delivery room while the placenta is still in the uterus by midwives and obstetricians or in an adjacent room after placental delivery by CB-bank trained personnel. In this study, the benefits and disadvantages between two different CB collection strategies were evaluated in order to improve CB bank methodology. DESIGN AND METHODS: Valencia CB bank maintains the two different collection strategies aforementioned. Before processing CB units, volume was calculated and samples were drawn for cell counts. After processing and before cryopreservation, samples for cell counts, CD34 analysis, viability, clonogenic assays and microbiology were drawn directly from the bags. We compared the efficiency of the two collection techniques. RESULTS: Obstetric date and umbilical CB was obtained from 848 vaginal (484 collected in uterus and 364 collected ex uterus). The proportion of excluded CB units before processing was 33% for ex uterus and 25% for in uterus. The difference was statistically significant. A larger volume and a higher number of total nucleated cells, CD34+ cells and CFUs were harvested in the in uterus collection group. INTERPRETATION AND CONCLUSIONS: Based on our findings, we conclude that the mode of collection influences the hematopoietic content of CB donations. Collection before placental delivery is the best approach to CB collection and allows optimizing CB bank methodology.

Antigens, CD34↗

Comparison between two strategies for umbilical cord blood collection.

The use of cord blood (CB) for transplantation has increased greatly in recent years. The collection strategy is the first step in collecting good-quality CB units. There are two main techniques for collecting CB from the umbilical vein: in the delivery room while the placenta is still in the uterus by midwives and obstetricians or in an adjacent room after placental delivery by CB bank trained personnel. In this study, the benefits and disadvantages between the two different CB collection strategies were evaluated, in order to improve CB bank methodology. Valencia CB bank maintains the two different collection strategies. CB was obtained from 569 vaginal and 70 caesarean deliveries and obstetrical and clinical charts were reviewed. Before processing CB units, volume was calculated and samples were drawn for cell counts. After processing and before cryopreservation samples were drawn for cell counts, CD34+cell analysis, viability, clonogenic assays and microbiology were drawn directly from the bags. We compared the efficiency of the two collection techniques. Obstetric data and umbilical CB were obtained from 569 vaginal (264 collected in utero and 305 collected ex utero) and 70 caesarean deliveries. The proportion of excluded CB units before processing was 33% for vaginal ex utero, 25% for vaginal in utero and 46% for caesarean deliveries. Differences were statistically significant. For vaginal deliveries a larger volume and a higher number of nucleated cells, percentage of CD34+ cells and colony-forming units (CFUs) were harvested in the in utero collection group. There was no statistical difference between CB collected after placental expulsion from vaginal and caesarean deliveries. Comparison between all vaginal and caesarean deliveries did not show any difference. We conclude that the mode of collection influences the haematopoietic content of CB donations. Collection before placental delivery is the best approach to CB collection and allows optimisation of CB bank methodology. Caesarean deliveries seem to contain similar progenitor content to vaginal deliveries.

Adult↗

Improving nitrogen removal in predenitrification-nitrification biofilters.

The effect on NH4-N removal rates in nitrification biofilters of filtered biodegradable COD and particulate COD leaving predenitrification biofilters was studied in a lab scale plant configured with the separated system of biofilters for secondary nitrogen removal from urban wastewaters. Applying a typical COD load of 11 kg/m3 x day to the predenitrification biofilter and maximizing its COD removal by adding nitrates or by operating an improved control of the internal recycle, only 60% removal of filtered biodegradable COD was found. This value corresponds to the complete removal of the readily biodegradable substrate (30% of influent filtered COD) and 36% of filtered slowly biodegradable substrate (50% of influent COD). The remaining 64% of the latter entered the nitrification biofilter, causing competition between heterotrophs and nitrifiers for dissolved oxygen in the inner layers of the biofilm. Consequently the nitrification rate had relatively low values (0.5 kgN/m3 x d) at 14 degrees C despite using dissolved oxygen levels of 6 mg/l. This behaviour may explain the lower nitrification rates obtained in some cases of nitrification biofilters compared to those in tertiary nitrification after activated sludge processes. The particulate COD entering the nitrification biofilter is associated with the suspended solids leaving the denitrification biofilter which are adsorbed by the external layers of the biofilm, increasing its thickness. The activity of the nitrifiers was affected because of a lack of oxygen when the thickness was left to grow considerably. Therefore no significant particulate COD effect is expected to occur as long as backwashing is carried out with the appropriate frequency.

Adsorption↗

Optimizing nitrogen removal in the BioDenitro process.

The potential and limits of different configurations of the BioDenitro-alternating process to suit the various design cases that can arise depending on the wastewater characteristics, space necessary and effluent nitrogen requirements were analysed through simulations of the activated sludge model No. 2. The first analysis involved the combination in one cycle of the main phase in the alternating reactors with an aerated phase having the two reactors in aerobic conditions and/or a hydraulic phase using the flow only in the anoxic reactor. This option has been found to have a very high potential for cases with strict requirements concerning effluent total nitrogen, but limited when the requirements are low effluent NH4-N, relatively high effluent total nitrogen and minimum solids and hydraulic retention times. When the latter conditions have to be fulfilled the incorporation of a post-aeration reactor to the alternating reactor was found to be very effective. In addition the configuration is very flexible because multiple combinations of post-aeration reactor volumes and in the duration of the different phases in the alternating reactors can be selected to achieve effluent nitrogen requirements. This flexibility is limited to the use of moderate values in the post-aeration reactor volumes and in the duration of the aerated phase. An experimental trial of the latter configuration was carried out and demonstrated its operational simplicity by achieving the desired nitrogen requirements in the effluent simply by changing the duration of the aerated phase for a given post-aeration reactor volume. From the experimental results an enhanced simultaneous nitrification-denitrification at the start of aeration in the alternating reactors was found and the ASM2 model was shown to have a satisfactory predictive capacity.

Bioreactors↗

Improving the predictions of ASM2d through modelling in practice.

The paper presents the adjustments carried out on the structure and in some default values of the kinetic coefficients of the ASM2d model in order to get an improved prediction for the experimental results obtained in pilot scale plants studies with different activated sludge treatment processes for carbon, nitrogen and phosphorous removal. In order to predict the high effluent filtered COD experimentally observed in high rate processes for carbon removal, a new model structure has been proposed, incorporating into the carbon model a soluble fraction of the slowly biodegradable substrate. Studies with the step feed and the alternating processes showed simultaneous nitrification-denitrification in aerated reactors which was predicted with increased values in the oxygen saturation coefficients for heterotrophic and autotrophic biomass. Both processes also showed loss of the denitrification capacity under unfavourable conditions, such us rains and low anoxic fraction, which required a very large decrease in the value of the reduction factor for denitrification so as to improve the predictions for effluent nitrate experimental results. Regarding phosphorus removal, the ASM2d model showed a satisfactory predictive capacity. For improved predictions of phosphorus release in anaerobic conditions, high values of the rate constant for storage of X(PHA) and low values of the anaerobic hydrolysis reduction factor were used. For phosphorus uptake in aerobic and anoxic conditions satisfactory predictions were obtained using the default values.

Biodegradation, Environmental↗

Standardized, unrelated donor cord blood transplantation in adults with hematologic malignancies.

The potential role of unrelated donor cord blood transplantation (UD-CBT) in adults remains unclear. This study reports the results of UD-CBT in 22 adults with hematologic malignancies following conditioning with thiotepa, busulfan, cyclophosphamide, and antithymocyte globulin in 21, with thiotepa, fludarabine, and antithymocyte globulin in 1, and graft-versus-host disease (GVHD) prophylaxis with cyclosporine and prednisone. Median age was 29 years (range, 18-46 years), and median weight was 69.5 kg (range, 41-85 kg). HLA match was 6 of 6 in 1 case, 5 of 6 in 13 cases, and 4 of 6 in 8 cases. Median number of nucleated cells infused was 1.71 x 10(7)/kg (range, 1.01 x 10(7)/kg to 4.96 x 10(7)/kg). All 20 patients surviving more than 30 days had myeloid engraftment, and only 1, who received the lowest cell dose, developed secondary graft failure. Median time to reach an absolute neutrophil count of at least 0.5 x 10(9)/L was 22 days (range, 13-52 days). Median time to platelets numbered at least 20 x 10(9)/L was 69 days (range, 49-153 days). Seven patients (32%) developed acute GVHD above grade II, and 9 of 10 patients at risk developed chronic GVHD, which became extensive in 4 patients. Twelve patients remained alive and disease-free 3 to 45 months after transplantation. Disease-free survival (DFS) at 1 year was 53%. Age strongly influenced DFS (P =.01). For patients aged 30 years or younger, the DFS at 1 year was 73%. These preliminary results suggest that UD-CBT should be considered a reasonable alternative in young adults with hematologic malignancy and no appropriate bone marrow donor.

Adult↗

Unrelated donor cord blood transplantation in adults with chronic myelogenous leukemia: results in nine patients from a single institution.

The potential role of unrelated donor cord blood transplantation (UD-CBT) in adults is not well established. We report the results of UD-CBT in nine adult patients with chronic myeloid leukemia (CML). The median age was 27 years (range, 19-41 years), and the median weight was 62 kg (range, 45-78 kg). At transplant, six patients were in chronic phase (five in first, and one in second), two in blast crisis, and one in accelerated phase. Eight had received intensive chemotherapy, and three had undergone autologous peripheral blood hematopoietic stem cell transplantation. Four had received interferon with no cytogenetic response, and only three underwent UD-CBT within 1 year of diagnosis. After serological typing for class I antigens, and high-resolution DNA typing for DRB1, the degree of HLA match between patients and cord blood (CB) units was 4/6 in six cases and 5/6 in three cases. The median number of nucleated cells infused was 1.7 x 10(7)/kg (range, 1.2 to 4.9 x 10(7)/kg), and was above 2 x 10(7)/kg in only two cases. All patients received thiotepa, busulfan, cyclophosphamide and anti-thymocyte globulin as conditioning; cyclosporine and prednisone for graft-versus-host disease (GVHD) prophylaxis; and G-CSF from day +7 until engraftment. All seven evaluable cases engrafted. The median time to reach an absolute neutrophil count > or =0.5 x 10(9)/l and > or =1 x 10(9)/l was 22 days (range, 19-52 days) and 28 days (range, 23-64 days), respectively. In the four patients evaluable for platelet recovery time to levels of > or =20 x 10(9) platelets/l, > or =50 x 10(9) platelets/l, and > or =100 x 10(9) platelets/l, these ranged from 50 to 128 days, 60 to 139 days, and 105 to 167 days, respectively. Three patients developed acute GVHD above grade II, and three of the five patients at risk developed extensive chronic GVHD. Four patients, all transplanted in chronic phase, remain alive in molecular remission more than 18, 19, 24 and 42 months after transplantation. These preliminary results suggest that UD-CBT may be considered a reasonable alternative in adults with CML who lack an appropriate bone marrow donor.

Acute Disease↗

Role of methylene blue-treated or fresh-frozen plasma in the response to plasma exchange in patients with thrombotic thrombocytopenic purpura.

Twenty patients with thrombotic thrombocytopenic purpura (TTP) underwent plasma exchange using either standard fresh-frozen plasma (Group A, n = 13) or methylene blue-treated plasma (Group B, n = 7). Both groups presented similar characteristics except that bilirubin values were higher in Group A (P < 0.05). The complete remission rate was higher in Group A than B (69% versus 57%). The mean number of procedures was higher in Group B (21 +/- 7 versus 11 +/- 3, P < 0.01) and the mean duration of hospitalization was also longer (37 +/- 12 d versus 22 +/- 11 d; P < 0.01). Our study shows that the use of methylene blue-treated fresh-frozen plasma to treat TTP is associated with a higher number of plasma exchanges and greater transfusion requirements without improving clinical results.

Adult↗

Development and verification of design and operation criteria for the step feed process with nitrogen removal.

The step feed process with three stages of denitrification-nitrification reactors has been studied using simulations in order to develop criteria for the optimum selection of the design parameters and to propose efficient operational strategies. To verify the simulation results experimental studies in a pilot plant of 1100 litres were carried out. The simulation studies showed that the optimum influent flow distribution to the three anoxic reactors is in the range of 40-40-20% and 33-33-34% depending on the wastewater characteristics and effluent requirements. These two latter conditions and in turn the influent flow distribution determine the anoxic and aerobic reactor volumes. The reduction of the dissolved oxygen in the two first aerobic reactors and the use of facultative zones in the final D-N stage are proposed as operational strategy. The experimental results proved the validity of the criteria developed for design and operation. A high capacity of the IAWQ activated sludge model No. 1 to predict the performance of the step feed process was observed.

Equipment Design↗

New simulators for the optimum management and operation of wastewater treatment plant.

This paper presents the basic description and the first full-scale implementation of a new kind of simulator specially designed to facilitate and improve the management and operation of modern wastewater treatment plants (WWTP). This new kind of simulator for plant operation is specifically adapted to every WWTP and the software is developed considering the common needs of the operators in plant exploitation. The internal structure of the plant operation simulator is based on a complete connection between the real data and the mathematical model of the plant. The software is then able to perform the processing, storage and management of the plant data and to predict the evolution of the process reading the required inputs from its stored files. The results obtained with the first application recommend the implementation of this new kind of simulators for plant operation in other treatment plants. However, it is important to note that the application of this technology implies a systematic and rigorous methodology in the acquisition and processing of the most significant plant data.

Data Collection↗

Cutaneous promyelocytic sarcoma at sites of vascular access and marrow aspiration. A characteristic localization of chloromas in acute promyelocytic leukemia?

Extramedullary disease (EMD) is a rare clinical event in acute promyelocytic leukemia (APL). Although the skin is involved in half of the reported EMD cases, the occurrence of cutaneous promyelocytic sarcoma (PS) has been described very rarely. We report here three cases of PS which have the peculiarity of appearing at sites of punctures for arterial and venous blood and marrow samples (sternal manubrium, antecubital fossa, wrist over the radial artery pulse, catheter insertion scar). At presentation, all patients had hyperleukocytosis and a morphologic diagnosis of microgranular acute promyelocytic leukemia variant confirmed at the genetic level by demonstration of the specific chromosomal translocation t(15;17). A BCR3 type PML/RARa transcript was documented in the two patients for whom diagnostic RT-PCR was available. Patients had morphologic bone marrow remission at the time the PS appeared. A predilection for the development of cutaneous PS at sites of previous vascular damage has been noted, but the pathogenesis remains largely unknown. A potential role for all-trans retinoic acid has been advocated, although one of the three patients in our series had received no ATRA. A review of the literature revealed six similar cases and hyperleukocytosis at diagnosis was a consistent finding in all of them. A careful physical examination of these particular sites in the follow-up of patients at risk, as well as cutaneous biopsy and laboratory examination of suspected lesions are strongly recommended.

Adolescent↗

Carboplatin plus cytarabine in the treatment of high-risk acute myeloblastic leukemia.

Thirty-one patients (20 male and 11 female; median age 51 years (16-79)) with high-risk acute myeloblastic leukemia (AML) (20 refractory AML and 11 secondary AML (s-AML) (four to myelodysplastic syndrome, five to chemo/radiotherapy, one to aplastic anemia and one blastic chronic myelogenous leukemia (B-CML)) were treated with CBDCA (300 mg/m2/day x 5 days in continuous i.v. infusion) plus intermediate-dose Ara-C (500 mg/m2/day x 3 days in rapid i.v. infusion). Nine patients (29%) achieved CR (five s-AML (three myelodysplastic syndromes, one CML and one ALL) and four refractory AML) and 11 patients had resistant disease. There were 11 early deaths (35%). Median disease-free survival of the nine responders was 4 months. The main toxicity was hematological, febrile episodes took place in nearly all the patients (96%). The CBDCA plus Ara-C regimen showed an evident antileukemic activity in high-risk leukemia. However, the lack of long-term disease-free survivors shows the need for innovative postremission strategies. The high initial response rate seen in AML secondary to myelodysplastic syndromes (MDS) warrants further investigation of CBDCA in combination regimens for MDS patients.

Adolescent↗