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2.
Sensors (Basel) ; 22(15)2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35898100

RESUMO

This paper presents a new synthetic dataset obtained from Gazebo simulations of an Unmanned Ground Vehicle (UGV) moving on different natural environments. To this end, a Husky mobile robot equipped with a tridimensional (3D) Light Detection and Ranging (LiDAR) sensor, a stereo camera, a Global Navigation Satellite System (GNSS) receiver, an Inertial Measurement Unit (IMU) and wheel tachometers has followed several paths using the Robot Operating System (ROS). Both points from LiDAR scans and pixels from camera images, have been automatically labeled into their corresponding object class. For this purpose, unique reflectivity values and flat colors have been assigned to each object present in the modeled environments. As a result, a public dataset, which also includes 3D pose ground-truth, is provided as ROS bag files and as human-readable data. Potential applications include supervised learning and benchmarking for UGV navigation on natural environments. Moreover, to allow researchers to easily modify the dataset or to directly use the simulations, the required code has also been released.


Assuntos
Robótica , Benchmarking , Meio Ambiente , Humanos , Espécies Reativas de Oxigênio , Software
3.
Sensors (Basel) ; 23(1)2022 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-36616647

RESUMO

The roles of emergency responders are challenging and often physically demanding, so it is essential that their duties are performed safely and effectively. In this article, we address real-time bio-signal sensor monitoring for responders in disaster scenarios. In particular, we propose the integration of a set of health monitoring sensors suitable for detecting stress, anxiety and physical fatigue in an Internet of Cooperative Agents architecture for search and rescue (SAR) missions (SAR-IoCA), which allows remote control and communication between human and robotic agents and the mission control center. With this purpose, we performed proof-of-concept experiments with a bio-signal sensor suite worn by firefighters in two high-fidelity SAR exercises. Moreover, we conducted a survey, distributed to end-users through the Fire Brigade consortium of the Provincial Council of Málaga, in order to analyze the firefighters' opinion about biological signals monitoring while on duty. As a result of this methodology, we propose a wearable sensor suite design with the aim of providing some easy-to-wear integrated-sensor garments, which are suitable for emergency worker activity. The article offers discussion of user acceptance, performance results and learned lessons.


Assuntos
Bombeiros , Robótica , Humanos , Robótica/métodos , Trabalho de Resgate , Comunicação
4.
Sensors (Basel) ; 21(23)2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34883848

RESUMO

Cloud robotics and advanced communications can foster a step-change in cooperative robots and hybrid wireless sensor networks (H-WSN) for demanding environments (e.g., disaster response, mining, demolition, and nuclear sites) by enabling the timely sharing of data and computational resources between robot and human teams. However, the operational complexity of such multi-agent systems requires defining effective architectures, coping with implementation details, and testing in realistic deployments. This article proposes X-IoCA, an Internet of robotic things (IoRT) and communication architecture consisting of a hybrid and heterogeneous network of wireless transceivers (H2WTN), based on LoRa and BLE technologies, and a robot operating system (ROS) network. The IoRT is connected to a feedback information system (FIS) distributed among multi-access edge computing (MEC) centers. Furthermore, we present SAR-IoCA, an implementation of the architecture for search and rescue (SAR) integrated into a 5G network. The FIS for this application consists of an SAR-FIS (including a path planner for UGVs considering risks detected by a LoRa H-WSN) and an ROS-FIS (for real-time monitoring and processing of information published throughout the ROS network). Moreover, we discuss lessons learned from using SAR-IoCA in a realistic exercise where three UGVs, a UAV, and responders collaborated to rescue victims from a tunnel accessible through rough terrain.


Assuntos
Desastres , Internet das Coisas , Robótica , Retroalimentação , Humanos , Trabalho de Resgate
5.
Sensors (Basel) ; 21(2)2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33466882

RESUMO

The urban population, worldwide, is growing exponentially and with it the demand for information on pollution levels, vehicle traffic, or available parking, giving rise to citizens connected to their environment. This article presents an experimental long range (LoRa) and low power consumption network, with a combination of static and mobile wireless sensors (hybrid architecture) to tune and validate concentrator placement, to obtain a large coverage in an urban environment. A mobile node has been used, carrying a gateway and various sensors. The Activation By Personalization (ABP) mode has been used, justified for urban applications requiring multicasting. This allows to compare the coverage of each static gateway, being able to make practical decisions about its location. With this methodology, it has been possible to provide service to the city of Malaga, through a single concentrator node. The information acquired is synchronized in an external database, to monitor the data in real time, being able to geolocate the dataframes through web mapping services. This work presents the development and implementation of a hybrid wireless sensor network of long range and low power, configured and tuned to achieve efficient performance in a mid-size city, and tested in experiments in a real urban environment.

6.
Rev Neurol ; 71(11): 407-420, 2020 Dec 01.
Artigo em Espanhol | MEDLINE | ID: mdl-33205387

RESUMO

INTRODUCTION: Motor fluctuations are one of the most common complications of Parkinson's disease and their treatment is still a complex matter. Therefore, from the Neurology Movement Disorders Group we present our clinical experience in the treatment of these complications, with the intention of it being useful in decision-making in daily clinical practice. DEVELOPMENT: Nineteen questions were developed based on a literature review and an open survey answered by members of this group. These issues were discussed in two phases, using the Delphi methodology. Considering the results of the survey, levodopa dose adjustment and dopamine agonists are the option with the best efficacy/tolerability ratio in the treatment of motor fluctuations. Rotigotine is useful in the motor fluctuations associated with gastroparesis, and intermittent subcutaneous apomorphine has positive effects in patients with unpredictable off periods. The most relevant adverse effect associated with dopamine agonists is impulse control disorder. Catechol-O-methyltransferase inhibitors are useful in the initial stages of motor fluctuations, especially in wearing off. Monoamine oxidase inhibitors are generally drugs that are well-tolerated and useful in motor fluctuations. If these measures are not effective, second-line treatments should be indicated on a case-by-case basis. CONCLUSION: The clinical profile of patients with Parkinson's disease is paramount in deciding the most appropriate therapy for the treatment of motor fluctuations.


TITLE: Experiencia clínica en el tratamiento de las fluctuaciones motoras en la enfermedad de Parkinson. Consenso Delphi de un grupo de expertos en trastornos del movimiento.Introducción. Las fluctuaciones motoras son una de las complicaciones más frecuentes en la enfermedad de Parkinson y su tratamiento sigue siendo complejo. Por ello, desde el Grupo de Trastornos del Movimiento de la Asociación Madrileña de Neurología presentamos nuestra experiencia clínica en el tratamiento de estas complicaciones, con la intención de que sea de utilidad en la toma de decisiones en la práctica clínica diaria. Desarrollo. Se elaboraron 19 preguntas a partir de una revisión bibliográfica y una encuesta abierta respondida por los miembros de dicho grupo. Dichas cuestiones se debatieron en dos fases, utilizando la metodología Delphi. Considerando los resultados de la encuesta, el ajuste de la dosis de levodopa y los agonistas dopaminérgicos son la opción con mejor relación eficacia/tolerabilidad en el tratamiento de las fluctuaciones motoras. La rotigotina es útil en las fluctuaciones motoras asociadas a gastroparesia, y la apomorfina subcutánea intermitente, en pacientes con off impredecible. El efecto adverso más relevante asociado a los agonistas dopaminérgicos es el trastorno del control de impulsos. Los inhibidores de la catecol-O-metiltransferasa son útiles en las fluctuaciones motoras de inicio, especialmente en el wearing off. Los inhibidores de la monoaminooxidasa son fármacos, en general, bien tolerados y útiles en las fluctuaciones motoras. En caso de que estas medidas no resulten eficaces, se deben indicar terapias de segunda línea de manera individualizada. Conclusión. El perfil clínico del paciente con enfermedad de Parkinson es primordial para decidir la terapia más adecuada en el tratamiento de las fluctuaciones motoras.


Assuntos
Antiparkinsonianos , Atividade Motora , Doença de Parkinson , Antiparkinsonianos/uso terapêutico , Inibidores de Catecol O-Metiltransferase/uso terapêutico , Consenso , Agonistas de Dopamina/uso terapêutico , Humanos , Levodopa/uso terapêutico , Atividade Motora/efeitos dos fármacos , Doença de Parkinson/tratamento farmacológico , Resultado do Tratamento
7.
Transfus Clin Biol ; 24(1): 9-14, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27865608

RESUMO

OBJECTIVES: The benefits of plasmapheresis (PA) for neurologic autoimmune diseases have been widely demonstrated. Little is known about the long-term neurologic prognosis and course after PA and immunosuppressive (IS) and/or intravenous immunoglobulin (IVIG) treatment. We aimed to analyse features associated with short-term response and long-term outcome and prognosis (neurologic status and mortality) of peripheral polyneuropathy (PP) and central nervous system acute inflammatory disease (CNSAID) treated with PA. PATIENTS AND METHODS: A descriptive, retrospective single-centre study from January 2005 to December 2012. RESULTS: There were 26 episodes, which included 16 CNSAID and 10 PP cases. First line therapy included PA (n=4), IS drugs (n=15), and IVIG (n=7). Responses were achieved in 80% and 50% of PP and CNSAID cases, respectively. For PP, first line treatment with IVIG and no IS treatment prior to or during PA were variables associated with short-term response (P=0.067), good or stable neurologic status at the end of follow-up (P=0.008), and lower mortality rate (P=0.008). For CNSAID, initial EDSS score≥7 (P=0.019) was related to long-term good or stable neurologic status. During the study period, 177 sessions were conducted; 3.4% had technical complications and 8.5% clinical complications. However, these incidents were all minor and no PA session had to be discontinued. CONCLUSION: The response rates achieved in our patients were similar to those of other research. PA has a safe profile but double-blind, controlled studies are needed to evaluate the synergy of sequential treatment with IGIV followed by PA and the possible benefit for long-term outcome.


Assuntos
Imunoglobulinas Intravenosas/uso terapêutico , Plasmaferese , Polineuropatias/terapia , Adolescente , Adulto , Idoso , Doenças do Sistema Nervoso Central/mortalidade , Doenças do Sistema Nervoso Central/terapia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Polineuropatias/mortalidade , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
8.
Am J Transplant ; 16(2): 484-96, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26517400

RESUMO

Acute cellular rejection occurs frequently during the first few weeks following liver transplantation. During this period, its molecular phenotype is confounded by peri- and postoperative proinflammatory events. To unambiguously define the molecular profile associated with rejection, we collected sequential biological specimens from 55 patients at least 3 years after liver transplantation who developed rejection during trials of intentional immunosuppression withdrawal. We analyzed liver tissue and blood samples obtained before initiation of drug withdrawal and at rejection, alongside blood samples collected during the weaning process. Gene expression profiling was conducted using whole-genome microarrays and real-time polymerase chain reaction. Rejection resulted in distinct blood and liver tissue transcriptional changes in patients who were either positive or negative for hepatitis C virus (HCV). Gene expression changes were mostly independent from pharmacological immunosuppression, and their magnitude correlated with severity of histological damage. Differential expression of a subset of genes overlapped across all conditions. These were used to define a blood predictive model that accurately identified rejection in HCV-negative, but not HCV-positive, patients. Changes were detectable 1-2 mo before rejection was diagnosed. Our results provide insight into the molecular processes underlying acute cellular rejection in liver transplantation and help clarify the potential utility and limitations of transcriptional biomarkers in this setting.


Assuntos
Biomarcadores/metabolismo , Perfilação da Expressão Gênica , Rejeição de Enxerto/diagnóstico , Tolerância Imunológica/genética , Transplante de Fígado , Complicações Pós-Operatórias , Suspensão de Tratamento , Feminino , Seguimentos , Regulação da Expressão Gênica , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/metabolismo , Sobrevivência de Enxerto , Humanos , Terapia de Imunossupressão , Imunossupressores/uso terapêutico , Hepatopatias/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
9.
Sensors (Basel) ; 15(10): 26143-69, 2015 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-26501278

RESUMO

Sustainable mobility requires a better management of the available infrastructure resources. To achieve this goal, it is necessary to obtain accurate data about road usage, in particular in urban areas. Although a variety of sensor alternates for urban traffic exist, they usually require extensive investments in the form of construction works for installation, processing means, etc. Wireless Sensor Networks (WSN) are an alternative to acquire urban traffic data, allowing for flexible, easy deployment. Together with the use of the appropriate sensors, like Bluetooth identification, and associate processing, WSN can provide the means to obtain in real time data like the origin-destination matrix, a key tool for trend monitoring which previously required weeks or months to be completed. This paper presents a system based on WSN designed to characterize urban traffic, particularly traffic trend monitoring through the calculation of the origin-destination matrix in real time by using Bluetooth identification. Additional sensors are also available integrated in different types of nodes. Experiments in real conditions have been performed, both for separate sensors (Bluetooth, ultrasound and laser), and for the whole system, showing the feasibility of this approach.

10.
Cell Death Differ ; 22(7): 1144-57, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25501596

RESUMO

Erythropoiesis is a tightly regulated process in which multipotential hematopoietic stem cells produce mature red blood cells. Here we show that deletion of poly(ADP-ribose) polymerase-2 (PARP-2) in mice leads to chronic anemia at steady state, despite increased erythropoietin plasma levels, a phenomenon not observed in mice lacking PARP-1. Loss of PARP-2 causes shortened lifespan of erythrocytes and impaired differentiation of erythroid progenitors. In erythroblasts, PARP-2 deficiency triggers replicative stress, as indicated by the presence of micronuclei, the accumulation of γ-H2AX (phospho-histone H2AX) in S-phase cells and constitutive CHK1 and replication protein A phosphorylation. Transcriptome analyses revealed the activation of the p53-dependent DNA-damage response pathways in PARP-2-deficient cells, culminating in the upregulation of cell-cycle and cell death regulators, concomitant with G2/M arrest and apoptosis. Strikingly, while loss of the proapoptotic p53 target gene Puma restored hematocrit levels in the PARP-2-deficient mice, loss of the cell-cycle regulator and CDK inhibitor p21 leads to perinatal death by exacerbating impaired fetal liver erythropoiesis in PARP-2-deficient embryos. Although the anemia displayed by PARP-2-deficient mice is compatible with life, mice die rapidly when exposed to stress-induced enhanced hemolysis. Our results pinpoint an essential role for PARP-2 in erythropoiesis by limiting replicative stress that becomes essential in the absence of p21 and in the context of enhanced hemolysis, highlighting the potential effect that might arise from the design and use of PARP inhibitors that specifically inactivate PARP proteins.


Assuntos
Replicação do DNA , Células Precursoras Eritroides/metabolismo , Eritropoese/fisiologia , Poli(ADP-Ribose) Polimerases/genética , Estresse Fisiológico/genética , Animais , Apoptose , Eritropoese/genética , Pontos de Checagem da Fase G2 do Ciclo Celular , Deleção de Genes , Histonas/metabolismo , Camundongos
11.
Actas Urol Esp ; 38(3): 143-9, 2014 Apr.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-24206626

RESUMO

OBJECTIVE: To analyze gene expression profiles of prostate cancer (PCa) with the aim of determining the relevant differentially expressed genes and subsequently ascertain whether this differential expression is maintained in post-prostatic massage (PPM) urine samples. MATERIAL AND METHODS: Forty-six tissue specimens (36 from PCa patients and 10 controls) and 158 urine PPM-urines (113 from PCa patients and 45 controls) were collected between December 2003 and May 2007. DNA microarrays were used to identify genes differentially expressed between tumour and control samples. Ten genes were technically validated in the same tissue samples by quantitative RT-PCR (RT-qPCR). Forty two selected differentially expressed genes were validated in an independent set of PPM-urines by qRT-PCR. RESULTS: Multidimensional scaling plot according to the expression of all the microarray genes showed a clear distinction between control and tumour samples. A total of 1047 differentially expressed genes (FDR≤.1) were indentified between both groups of samples. We found a high correlation in the comparison of microarray and RT-qPCR gene expression levels (r=.928, P<.001). Thirteen genes maintained the same fold change direction when analyzed in PPM-urine samples and in four of them (HOXC6, PCA3, PDK4 and TMPRSS2-ERG), these differences were statistically significant (P<.05). CONCLUSION: The analysis of PCa by DNA microarrays provides new putative mRNA markers for PCa diagnosis that, with caution, can be extrapolated to PPM-urines.


Assuntos
Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica , Proteínas de Neoplasias/genética , Neoplasias da Próstata/genética , RNA Mensageiro/análise , RNA Neoplásico/análise , Adenocarcinoma/química , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Adenocarcinoma/urina , Idoso , Antígenos de Neoplasias/biossíntese , Antígenos de Neoplasias/genética , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/urina , Proteínas de Homeodomínio/biossíntese , Proteínas de Homeodomínio/genética , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Proteínas de Neoplasias/análise , Proteínas de Neoplasias/biossíntese , Estadiamento de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas de Fusão Oncogênica/biossíntese , Proteínas de Fusão Oncogênica/genética , Tamanho do Órgão , Próstata/química , Próstata/patologia , Neoplasias da Próstata/química , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/urina , Proteínas Serina-Treonina Quinases/biossíntese , Proteínas Serina-Treonina Quinases/genética , Piruvato Desidrogenase Quinase de Transferência de Acetil , RNA Mensageiro/urina , RNA Neoplásico/urina , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Técnica de Subtração
12.
Clin Microbiol Infect ; 18(8): E273-82, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22524533

RESUMO

Although the connection of microRNAs (miRNAs) to some diseases is well established, their involvement in chronic infections such as Helicobacter pylori has received less attention. The aim was to compare miRNA expression profiling in patients with duodenal ulcer (DU) due to H. pylori infection with that in infected patients without DU and in uninfected patients. The miRNA expression profile was determined by microarrays in antral mucosal samples from well-characterized dyspeptic patients (n = 46). The most significant set of miRNAs was subsequently analysed in an independent validation group of patients (n = 42). Transcripts for IL8, IL12p40, IL12p35 and IL23p19, the signalling molecules MYD88, GATA6, SOCS2 and STAT6 and H. pylori virulence factors cagA and VacA were analysed. Microarray experiments showed that 17 miRNAs were deregulated in the mucosa of H. pylori-infected patients. No significant differences were observed between normal and DU patients. PCR confirmed the up-regulation of miR-9, miR-146a, miR-155 and miR-650 and the down-regulation of miR-96 and miR-204 in the independent validation set of patients. Importantly, miR-9, miR-96, miR-146a and miR-650 expression was specific to chronic-active gastritis. H. pylori-infected patients showed higher levels of IL8 and IL12p40 mRNAs and lower levels of GATA6 and SOCS2 mRNAs. The antral mucosa of patients with non-active or chronic-active gastritis showed significantly lower levels of GATA6, MYD88, SOCS2 and STAT6 mRNAs compared with patients without gastritis. The down-regulation of these factors was not correlated with the expression of any of the validated miRNAs. The exact role of the miRNA changes observed will require further study.


Assuntos
Úlcera Duodenal/imunologia , Perfilação da Expressão Gênica , Infecções por Helicobacter/imunologia , Helicobacter pylori/patogenicidade , Interações Hospedeiro-Patógeno , MicroRNAs/genética , Adulto , Úlcera Duodenal/microbiologia , Feminino , Mucosa Gástrica/imunologia , Mucosa Gástrica/patologia , Infecções por Helicobacter/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Transdução de Sinais/genética
13.
Am J Transplant ; 11(9): 1916-26, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21827613

RESUMO

A proportion of transplant recipients can spontaneously accept their grafts in the absence of immunosuppression (operational tolerance). Previous studies identified blood transcriptional and cell-phenotypic markers characteristic of either liver or kidney tolerant recipients. However, the small number of patients analyzed and the use of different transcriptional platforms hampered data interpretation. In this study we directly compared samples from kidney and liver tolerant recipients in order to identify potential similarities in immune-related parameters. Liver and kidney tolerant recipients differed in blood expression and B-cell immunophenotypic patterns and no significant overlaps were detectable between them. Whereas some recipients coincided in specific NK-related transcripts, this observation was not reproducible in all cohorts analyzed. Our results reveal that certain immune features, but not others, are consistently present across all cohorts of operationally tolerant recipients. This provides a set of reproducible biomarkers that should be explored in future large-scale immunomonitoring trials.


Assuntos
Tolerância Imunológica , Transplante de Rim , Transplante de Fígado , Transcrição Gênica , Adulto , Idoso , Linfócitos B/imunologia , Humanos , Imunofenotipagem , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase
14.
Am J Transplant ; 10(12): 2604-14, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21114641

RESUMO

Due to its low level of nephrotoxicity and capacity to harness tolerogenic pathways, sirolimus (SRL) has been proposed as an alternative to calcineurin inhibitors in transplantation. The exact mechanisms underlying its unique immunosuppressive profile in humans, however, are still not well understood. In the current study, we aimed to depict the in vivo effects of SRL in comparison with cyclosporin A (CSA) by employing gene expression profiling and multiparameter flow cytometry on blood cells collected from stable kidney recipients under immunosuppressant monotherapy. SRL recipients displayed an increased frequency of CD4 + CD25highFoxp3 + T cells. However, this was accompanied by an increased number of effector memory T cells and by enrichment in NFkB-related pro-inflammatory expression pathways and monocyte and NK cell lineage-specific transcripts. Furthermore, measurement of a transcriptional signature characteristic of operationally tolerant kidney recipients failed to detect differences between SRL and CSA-treated recipients. In conclusion, we show here that the blood transcriptional profile induced by SRL monotherapy in vivo does not resemble that of operationally tolerant recipients and is dominated by innate immune cells and NFkB-related pro-inflammatory events. These data provide novel insights on the complex effects of SLR on the immune system in clinical transplantation.


Assuntos
Ciclosporina/uso terapêutico , Imunossupressores/uso terapêutico , Transplante de Rim/imunologia , Sirolimo/uso terapêutico , Linfócitos T/imunologia , Contagem de Linfócito CD4 , Citometria de Fluxo , Perfilação da Expressão Gênica , Humanos , Imunidade Inata/efeitos dos fármacos , Fenótipo , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo
15.
Am J Transplant ; 10(10): 2296-304, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20883560

RESUMO

We report the results of a prospective randomized controlled trial in liver transplantation assessing the efficacy and safety of antithymocyte globulin (ATG-Fresenius) plus tacrolimus monotherapy at gradually decreasing doses. Patients were randomized to either: (a) standard-dose tacrolimus plus steroids;or (b) peritransplant ATG-Fresenius plus reduced-dose tacrolimus monotherapy followed by weaning of tacrolimus starting 3 months after transplantation. The primary end-point was the achievement of very low-dose tacrolimus (every-other-day or once daily dose with <5 ng/mL trough levels) at 12 months after transplantation. Acute rejection occurring during the first 3 months after transplantation was more frequent in the ATG group (52.4% vs. 25%). Moreover, late acute rejection episodes occurred in all recipients in whom weaning was attempted and no recipients reached the primary end-point. This motivated the premature termination of the trial. Tacrolimus trough levels were lower in the ATG-Fresenius group but no benefits in terms of improved renal function, lower metabolic complications or increased prevalence of tolerance-related biomarkers were observed. In conclusion, the use of ATG-Fresenius and tacrolimus at gradually decreasing doses was associated with a high rate of rejection, did not allow for the administration of very low doses of tacrolimus and failed to provide detectable clinical benefits. ClinicalTrials.gov identifier: NCT00436722.


Assuntos
Soro Antilinfocitário/administração & dosagem , Transplante de Fígado/métodos , Tacrolimo/administração & dosagem , Adulto , Feminino , Rejeição de Enxerto/epidemiologia , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Tacrolimo/efeitos adversos
16.
Neurologia ; 24(2): 113-24, 2009 Mar.
Artigo em Espanhol | MEDLINE | ID: mdl-19322690

RESUMO

INTRODUCTION: Currently used antiparkinsonian drugs neither stop nor slow-down the progressive nature of the disease. The final phase of PD is characterized by the presence of symptoms and signs resistant to dopaminergic agents, such as depression, dementia, freezing and falls. Therefore, it is urgent to develop therapies able to positively modify this outcome. Despite neuroprotection is a research priority in PD, no effective strategies have been found so far. METHOD: A key informants study was conducted. A group of experts in PD fulfilled a questionnaire of 10 questions to explore the most important topics related to neuroprotection. Afterwards a consensus about the current situation of neuroprotection in PD was established and future directions of development were suggested. RESULTS: Most of the answers emphasized the need of new concepts, the limitations of animal models and the difficulties in the difficulties in demonstrating a neuroprotective effects in humans owing to a lack of biomarkers. Some of the experts believe that we are already exerting a disease modifying effect. CONCLUSIONS: The concept of neuroprotection should be widened. Animal models should be improved. A reliable biomarker to start neuroprotective therapies long before the appearance of motor symptoms and to evaluate the neuroprotective effect of any therapy should be urgently developed.


Assuntos
Antiparkinsonianos/uso terapêutico , Consenso , Fármacos Neuroprotetores/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/prevenção & controle , Animais , Biomarcadores/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Humanos , Doença de Parkinson/fisiopatologia , Guias de Prática Clínica como Assunto , Inquéritos e Questionários , Resultado do Tratamento
18.
Leukemia ; 22(7): 1368-76, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18480837

RESUMO

To explore the gene expression signature in essential thrombocythemia (ET) patients in relation to JAK2V617F mutational status, expression profiling in circulating granulocytes was performed. Twenty ET were studied by microarray analysis and the results were confirmed by real-time quantitative RT-PCR in 40 ET patients, not receiving cytoreductive treatment. A heterogeneous molecular signature characterized by two main gene expression patterns was found: one with an upregulation of inflammatory genes related to neutrophil activation and thrombosis, and the other with significantly lower expression of these genes. Supervised clustering analysis showed 30 genes differentially expressed between JAK2V617F-negative and JAK2V617F-positive ET patients. Among the JAK2V617F-negative, a set of 14 genes (CISH, C13orf18, CCL3, PIM1, MAFF, SOCS3, ID2, GADD45B, KLF5, TNF, LAMB3, HRH4, TAGAP and TRIB1) showed an abnormal expression pattern. In this group of patients, CISH, SOCS2, SOCS3 and PIM1 genes, all involved in JAK-STAT signalling pathway, presented a lower expression. A two-gene predictor model was built comprising FOSB and CISH genes, which were the best discriminators of JAK2V617F status. In conclusion, JAK2V617F-negative ET patients present a characteristic gene expression profile, different from JAK2V617F-positive patients. Other pathways, besides JAK-STAT, might be implicated in the pathophysiology of JAK2V617F-negative ET patients.


Assuntos
Perfilação da Expressão Gênica , Janus Quinase 2/genética , Mutação , Trombocitemia Essencial/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Transcrição STAT/fisiologia , Transdução de Sinais
19.
An Med Interna ; 22(5): 213-6, 2005 May.
Artigo em Espanhol | MEDLINE | ID: mdl-16001935

RESUMO

BACKGROUND: Autologous peripheral blood stem cell transplantation (PBSCT) is a procedure frequently used as therapy for hematological malignancies, in which infectious complications are a major cause of morbimortality. The duration and intensity of neutropenia, indwelling central venous catheters, and mucosa chemotherapy-induced damage, contribute to increase infection rates. We have retrospectively review the incidence of febrile episodes and microbiological documented infections (MDI) in patients with multiple myeloma (MM) undergoing PBSCT. PATIENTS AND METHODS: We have retrospectively analyzed 56 PBSCT in patients diagnosed of MM between 1995 and 2002 in our hospital. RESULTS: 34 patients showed fever: 19 fever of unknown origin; 5 clinically documented infections and 10 patients MDI. We isolated 5 pathogens gram negative and 4 gram positive. We observed 2 infections associated to indwelling central venous catheters and 1 MDI due to simplex Herpes Virus. Two patients died due to infectious complications. CONCLUSIONS: The incidence of febrile episodes in our patients is similar to those previously reported as well, duration of neutropenia associated to PBSCT. We have observed a slightly higher incidence of gram negative pathogens.


Assuntos
Infecções Bacterianas/epidemiologia , Febre/epidemiologia , Mieloma Múltiplo/cirurgia , Transplante de Células-Tronco de Sangue Periférico , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Antibacterianos/uso terapêutico , Antineoplásicos/efeitos adversos , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/etiologia , Cateterismo Venoso Central/efeitos adversos , Feminino , Febre/etiologia , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Negativas/etiologia , Herpes Simples/epidemiologia , Herpes Simples/etiologia , Mortalidade Hospitalar , Humanos , Hospedeiro Imunocomprometido , Incidência , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Neutropenia/complicações , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Condicionamento Pré-Transplante/efeitos adversos , Transplante Autólogo , Resultado do Tratamento
20.
An. med. interna (Madr., 1983) ; 22(5): 213-216, mayo 2005. tab
Artigo em Es | IBECS | ID: ibc-039332

RESUMO

Introducción: El trasplante autólogo de progenitores hematopoyéticos de sangre periférica (TASPE), es un procedimiento frecuentemente empleado en el tratamiento de las hemopatías malignas, siendo la morbimortalidad atribuible a las infecciones un factor determinante en el resultado final del mismo. La duración e intensidad de la neutropenia, la presencia de catéteres venosos centrales y la alteración de las mucosas contribuyen a una mayor incidencia de infecciones. Revisamos de manera retrospectiva la incidencia de episodios febriles y en especial de infecciones microbiológicamente documentadas (IMD) en pacientes afectos de mieloma múltiple (MM) sometidos a TASPE. Pacientes y métodos: Análisis retrospectivo de una serie de 56 pacientes con MM sometidos a TASPE en nuestro hospital entre 1995 y 2002. Resultados: Treinta y cuatro pacientes presentaron fiebre: 19 episodios febriles sin foco; 5 episodios febriles clínicamente documentados y 10 pacientes IMD. Se aislaron 5 microorganismos gram negativos frente a 4 gram positivos. Se evidenció infección de catéter en 2 casos. Sólo observamos una IMD de etiología vírica por virus Herpes simple (VHS). Dos pacientes fallecieron como consecuencia del proceso infeccioso. Conclusiones: El porcentaje de procesos febriles en nuestra serie es similar al descrito en la literatura, así como la duración de la neutropenia asociada al TASPE. Observamos un discreto predominio de la infecciones por gram negativos


Background: Autologous peripheral blood stem cell transplantation (PBSCT) is a procedure frequently used as therapy for hematological malignancies, in wich infectious complications are a major cause of morbimortality. The duration and intensity of neutropenia, indwelling central venous catheters, and mucosa chemotherapy-induced damage, contribute to increase infection rates. We have retrospectively review the incidence of febrile episodes and microbiological documented infections (MDI) in patients with multiple myeloma (MM) undergoing PBSCT. Patients and methods: We have retrospectively analized 56 PBSCT in patients diagnosed of MM between 1995 and 2002 in our hospital. Results: 34 patients showed fever: 19 fever of unknown origin; 5 clinically documented infections and 10 patients MDI. We isolated 5 pathogens gram negative and 4 gram positive. We observed 2 infections associated to indwelling central venous catheters and 1 MDI due to simplex Herpes Virus. Two patiens died due to infectious complications. Conclusions: The incidence of febrile episodes in our patients is similar to those previously reported as well, duration of neutropenia associated to PBSCT. We have observed a slightly higher incidence of gram negative pathogens


Assuntos
Adulto , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/patologia , Transplante Autólogo/patologia , Transplante Autólogo/fisiologia , Células-Tronco Hematopoéticas/imunologia , Mieloma Múltiplo/complicações , Herpes Simples/etiologia , Células-Tronco Hematopoéticas/fisiologia , Tratamento Farmacológico/métodos , Tratamento Farmacológico
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