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1.
J Neuroeng Rehabil ; 17(1): 56, 2020 04 25.
Artículo en Inglés | MEDLINE | ID: mdl-32334622

RESUMEN

BACKGROUND: Tremor is a cardinal symptom of Parkinson's disease (PD) that may cause severe disability. As such, objective methods to determine the exact characteristics of the tremor may improve the evaluation of therapy. This methodology study aims to validate the utility of two objective technical methods of recording Parkinsonian tremor and evaluate their ability to determine the effects of Deep Brain Stimulation (DBS) of the subthalamic nucleus and of vision. METHODS: We studied 10 patients with idiopathic PD, who were responsive to L-Dopa and had more than 1 year use of bilateral subthalamic nucleus stimulation. The patients did not have to display visible tremor to be included in the study. Tremor was recorded with two objective methods, a force platform and a 3 dimensional (3D) motion capture system that tracked movements in four key proximal sections of the body (knee, hip, shoulder and head). They were assessed after an overnight withdrawal of anti-PD medications with DBS ON and OFF and with eyes open and closed during unperturbed and perturbed stance with randomized calf vibration, using a randomized test order design. RESULTS: Tremor was detected with the Unified Parkinson's Disease Rating Scale (UPDRS) in 6 of 10 patients but only distally (hands and feet) with DBS OFF. With the force platform and the 3D motion capture system, tremor was detected in 6 of 10 and 7 of 10 patients respectively, mostly in DBS OFF but also with DBS ON in some patients. The 3D motion capture system revealed that more than one body section was usually affected by tremor and that the tremor amplitude was non-uniform, but the frequency almost identical, across sites. DBS reduced tremor amplitude non-uniformly across the body. Visual input mostly reduced tremor amplitude with DBS ON. CONCLUSIONS: Technical recording methods offer objective and sensitive detection of tremor that provide detailed characteristics such as peak amplitude, frequency and distribution pattern, and thus, provide information that can guide the optimization of treatments. Both methods detected the effects of DBS and visual input but the 3D motion system was more versatile in that it could detail the presence and properties of tremor at individual body sections.


Asunto(s)
Imagenología Tridimensional/métodos , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/terapia , Temblor/diagnóstico , Anciano , Estimulación Encefálica Profunda/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Núcleo Subtalámico/fisiología , Temblor/etiología
2.
J Clin Monit Comput ; 32(3): 429-437, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28602010

RESUMEN

The purpose of this concept study was to investigate the possibility of automatic mean arterial pressure (MAP) regulation in a porcine heart-beating brain death (BD) model. Hemodynamic stability of BD donors is necessary for maintaining acceptable quality of donated organs for transplantation. Manual stabilization is challenging, due to the lack of vasomotor function in BD donors. Closed-loop stabilization therefore has the potential of increasing availability of acceptable donor organs, and serves to indicate feasibility within less demanding patient groups. A dynamic model of nitroglycerine pharmacology, suitable for controller synthesis, was identified from an experiment involving an anesthetized pig, using a gradient-based output error method. The model was used to synthesize a robust PID controller for hypertension prevention, evaluated in a second experiment, on a second, brain dead, pig. Hypotension was simultaneously prevented using closed-loop controlled infusion of noradrenaline, by means of a previously published controller. A linear model of low order, with variable (uncertain) gain, was sufficient to describe the dynamics to be controlled. The robustly tuned PID controller utilized in the second experiment kept the MAP within a user-defined range. The system was able to prevent hypertension, exceeding a reference of 100 mmHg by more than 10%, during 98% of a 12 h experiment. This early work demonstrates feasibility of the investigated modelling and control synthesis approach, for the purpose of maintaining normotension in a porcine BD model. There remains a need to characterize individual variability, in order to ensure robust performance over the expected population.


Asunto(s)
Anestesia por Circuito Cerrado/métodos , Presión Arterial , Muerte Encefálica , Monitoreo Fisiológico/instrumentación , Monitoreo Fisiológico/métodos , Animales , Análisis de los Gases de la Sangre , Hemodinámica , Humanos , Hipertensión , Hipotensión , Modelos Animales , Contracción Miocárdica , Porcinos
3.
Proc Natl Acad Sci U S A ; 111(14): 5409-14, 2014 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-24706865

RESUMEN

One hallmark of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) is infiltration of leukocytes into the CNS, where chemokines and their receptors play a major mediatory role. CX3CR1 is a chemokine receptor involved in leukocyte adhesion and migration and hence a mediator of immune defense reactions. The role of CX3CR1 in MS and EAE pathogenesis however remains to be fully assessed. Here, we demonstrate CX3CR1 mRNA expression on inflammatory cells within active plaque areas in MS brain autopsies. To test whether blocking CNS infiltration of peripheral leukocytes expressing CX3CR1 would be a suitable treatment strategy for MS, we developed a selective, high-affinity inhibitor of CX3CR1 (AZD8797). The compound is active outside the CNS and AZD8797 treatment in Dark Agouti rats with myelin oligodendrocyte glycoprotein-induced EAE resulted in reduced paralysis, CNS pathology, and incidence of relapses. The compound is effective when starting treatment before onset, as well as after the acute phase. This treatment strategy is mechanistically similar to, but more restricted than, current very late antigen-4-directed approaches that have significant side effects. We suggest that blocking CX3CR1 on leukocytes outside the CNS could be an alternative approach to treat MS.


Asunto(s)
Encéfalo/metabolismo , Modelos Animales de Enfermedad , Esclerosis Múltiple/patología , Receptores de Quimiocina/antagonistas & inhibidores , Animales , Receptor 1 de Quimiocinas CX3C , Enfermedad Crónica , Ratas , Receptores de Quimiocina/metabolismo , Recurrencia
4.
IEEE Trans Neural Netw Learn Syst ; 34(8): 4841-4855, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34767516

RESUMEN

This article addresses the distributed cooperative control design for a class of sampled-data teleoperation systems with multiple slave mobile manipulators grasping an object in the presence of communication bandwidth limitation and time delays. Discrete-time information transmission with time-varying delays is assumed, and the Round-Robin (RR) scheduling protocol is used to regulate the data transmission from the multiple slaves to the master. The control task is to guarantee the task-space position synchronization between the master and the grasped object with the mobile bases in a fixed formation. A fully distributed control strategy including neural-network-based task-space synchronization controllers and neural-network-based null-space formation controllers is proposed, where the radial basis function (RBF) neural networks with adaptive estimation of approximation errors are used to compensate the dynamical uncertainties. The stability and the synchronization/formation features of the single-master-multiple-slaves (SMMS) teleoperation system are analyzed, and the relationship among the control parameters, the upper bound of the time delays, and the maximum allowable sampling interval is established. Experiments are implemented to validate the effectiveness of the proposed control algorithm.

5.
Percept Mot Skills ; 130(4): 1400-1414, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37119199

RESUMEN

The human vestibulo-ocular reflex (VOR) leads to maintenance of the acuity of an image on the retina and contributes to the perception of orientation during high acceleration head movements. Our objective was to determine whether vision affects the horizontal VOR by assessing and comparing the performance at the boundaries of contribution of: (a) unrestricted visual information and (b) no visual information. Understanding how the VOR performs under both lighted and unlighted conditions is of paramount importance to avoiding falls, perhaps particularly among the elderly. We tested 23 participants (M age = 35.3 years, standard error of mean (SEM) = 2.0 years). The participants were tested with the video Head Impulse Test (vHIT), EyeSeeCam from Interacoustics™, which assesses whether VOR is of the expected angular velocity compared to head movement angular velocity. The vHIT tests were performed under two conditions: (a) in a well-lit room and (b) in complete darkness. The VOR was analyzed by evaluating the gain (quotient between eye and head angular velocity) at 40, 60 and 80 ms time stamps after the start of head movement. Additionally, we calculated the approximate linear gain between 0-100 ms through regression. The gain decreased significantly faster across time stamps in complete darkness (p < .001), by 10% in darkness compared with a 2% decrease in light. In complete darkness, the VOR gain gradually declined, reaching a marked reduction at 80 ms by 10% (p < .001), at which the head velocities were 150°/second or faster. The approximate linear gain value was not significantly different in complete darkness and in light. These findings suggest that information from the visual system can modulate the high velocity VOR. Subsequently, fast head turns might cause postural imbalance and momentary disorientation in poor light in people with reduced sensory discrimination or motor control, like the elderly.


Asunto(s)
Reflejo Vestibuloocular , Visión Ocular , Humanos , Anciano , Adulto , Oscuridad , Movimientos de la Cabeza , Aceleración
6.
Sci Rep ; 11(1): 23550, 2021 12 07.
Artículo en Inglés | MEDLINE | ID: mdl-34876604

RESUMEN

Parkinson's disease (PD) is characterized by rigidity, akinesia, postural instability and tremor. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) reduces tremor but the effects on postural instability are inconsistent. Another component of postural control is the postural strategy, traditionally referred to as the ankle or hip strategy, which is determined by the coupling between the joint motions of the body. We aimed to determine whether DBS STN and vision (eyes open vs. eyes closed) affect the postural strategy in PD in quiet stance or during balance perturbations. Linear motion was recorded from the knee, hip, shoulder and head in 10 patients with idiopathic PD with DBS STN (after withdrawal of other anti-PD medication), 25 younger adult controls and 17 older adult controls. Correlation analyses were performed on anterior-posterior linear motion data to determine the coupling between the four positions measured. All participants were asked to stand for a 30 s period of quiet stance and a 200 s period of calf vibration. The 200 s vibration period was subdivided into four 50 s periods to study adaptation between the first vibration period (30-80 s) and the last vibration period (180-230 s). Movement was recorded in patients with PD with DBS ON and DBS OFF, and all participants were investigated with eyes closed and eyes open. DBS settings were randomized and double-blindly programmed. Patients with PD had greater coupling of the body compared to old and young controls during balance perturbations (p ≤ 0.046). Controls adopted a strategy with greater flexibility, particularly using the knee as a point of pivot, whereas patients with PD adopted an ankle strategy, i.e., they used the ankle as the point of pivot. There was higher flexibility in patients with PD with DBS ON and eyes open compared to DBS OFF and eyes closed (p ≤ 0.011). During balance perturbations, controls quickly adopted a new strategy that they retained throughout the test, but patients with PD were slower to adapt. Patients with PD further increased the coupling between segmental movement during balance perturbations with DBS ON but retained a high level of coupling with DBS OFF throughout balance perturbations. The ankle strategy during balance perturbations in patients with PD was most evident with DBS OFF and eyes closed. The increased coupling with balance perturbations implies a mechanism to reduce complexity at a cost of exerting more energy. Strategic alterations of posture were altered by DBS in patients with PD and were delayed. Our findings therefore show that DBS does not fully compensate for disease-related effects on posture.


Asunto(s)
Estimulación Encefálica Profunda , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/terapia , Equilibrio Postural/fisiología , Adaptación Fisiológica , Adulto , Anciano , Articulación del Tobillo/fisiopatología , Estudios de Casos y Controles , Señales (Psicología) , Método Doble Ciego , Femenino , Humanos , Articulación de la Rodilla/fisiopatología , Masculino , Persona de Mediana Edad , Movimiento/fisiología , Postura/fisiología , Vibración/efectos adversos , Visión Ocular/fisiología , Adulto Joven
7.
PLoS One ; 16(12): e0259862, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34905546

RESUMEN

Parkinson's disease (PD) can produce postural abnormalities of the standing body position such as kyphosis. We investigated the effects of PD, deep brain stimulation (DBS) in the subthalamic nucleus (STN), vision and adaptation on body position in a well-defined group of patients with PD in quiet standing and during balance perturbations. Ten patients with PD and 25 young and 17 old control participants were recruited. Body position was measured with 3D motion tracking of the ankle, knee, hip, shoulder and head. By taking the ankle as reference, we mapped the position of the joints during quiet standing and balance perturbations through repeated calf muscle vibration. We did this to explore the effect of PD, DBS in the STN, and vision on the motor learning process of adaptation in response to the repeated stimulus. We found that patients with PD adopt a different body position with DBS ON vs. DBS OFF, to young and old controls, and with eyes open vs. eyes closed. There was an altered body position in PD with greater flexion of the head, shoulder and knee (p≤0.042) and a posterior position of the hip with DBS OFF (p≤0.014). With DBS ON, body position was brought more in line with the position taken by control participants but there was still evidence of greater flexion at the head, shoulder and knee. The amplitude of movement during the vibration period decreased in controls at all measured sites with eyes open and closed (except at the head in old controls with eyes open) showing adaptation which contrasted the weaker adaptive responses in patients with PD. Our findings suggest that alterations of posture and greater forward leaning with repeated calf vibration, are independent from reduced movement amplitude changes. DBS in the STN can significantly improve body position in PD although the effects are not completely reversed. Patients with PD maintain adaptive capabilities by leaning further forward and reducing movement amplitude despite their kyphotic posture.


Asunto(s)
Adaptación Fisiológica , Estimulación Encefálica Profunda/métodos , Cifosis/terapia , Enfermedad de Parkinson/terapia , Equilibrio Postural/fisiología , Anciano , Articulación del Tobillo/fisiología , Estudios de Casos y Controles , Femenino , Globo Pálido/fisiopatología , Cabeza/fisiología , Articulación de la Cadera/fisiología , Humanos , Articulación de la Rodilla/fisiología , Cifosis/etiología , Cifosis/fisiopatología , Masculino , Persona de Mediana Edad , Movimiento/fisiología , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/fisiopatología , Postura/fisiología , Articulación del Hombro/fisiología , Núcleo Subtalámico/fisiopatología
8.
Gait Posture ; 86: 217-225, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33765547

RESUMEN

BACKGROUND: The characteristics of Parkinson's disease (PD) include postural instability and resting tremor. However, reductions of tremor amplitude do not always improve postural stability. RESEARCH QUESTION: What is the effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on spectral analysis of body movement in patients with PD when tested without anti-PD medication? The effect of visual cues was also studied. METHODS: Ten patients with PD (mean age 64.3 years, range 59-69 years) and 17 control participants (mean age 71.2 years, range 65-79 years) were recruited. Spectral power following a period of quiet stance (35 s) was analysed in three different spectral power bands (0-4 Hz, 4-7 Hz and 7-25 Hz). Motion markers were secured to the head, shoulder, hip, and knee, which recorded movements in two directions, the anteroposterior and lateral. RESULTS: DBS STN significantly changed the spectral distribution pattern across the body in the anteroposterior (p = 0.029) and lateral directions (p ≤ 0.003). DBS predominantly reduced spectral power at the head (p ≤ 0.037) and shoulder (p ≤ 0.031) in the lateral direction. The spectral power of the lower and upper body in patients with PD, with DBS ON, were more similar to the control group, than to DBS OFF. Visual cues mainly reduced spectral power in the anteroposterior direction at the shoulder (p ≤ 0.041) in controls and in patients with PD with DBS ON. SIGNIFICANCE: There is an altered postural strategy in patients with PD with DBS ON as shown by an altered spectral power distribution pattern across body segments and a reduction of spectral power in the lateral direction at the head and shoulder. A reduction of spectral power in controls and in patients with PD with DBS ON suggests that visual cues are able to reduce spectral power to some extent, but not with DBS OFF where postural sway and power are larger.


Asunto(s)
Estimulación Encefálica Profunda , Movimiento/fisiología , Enfermedad de Parkinson/terapia , Anciano , Señales (Psicología) , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/fisiopatología , Equilibrio Postural/fisiología , Núcleo Subtalámico/fisiología
9.
Comput Biol Med ; 122: 103828, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32658731

RESUMEN

The standard approach to the evaluation of tremor in medical practice is subjective scoring. The objective of this study was to show that signal processing of physiological data, that are known to be altered by tremor in Parkinson's disease (PD), can quantify the postural dynamics and the effects of DBS. We measured postural control and its capacity to adapt to balance perturbations with a force platform and perturbed balance by altering visual feedback and using pseudo-random binary sequence perturbations (PRBS) of different durations. Our signal processing involved converting the postural control data into spectral power with Fast-Fourier Transformation across a wide bandwidth and then subdividing this into three bands (0-4 Hz, 4-7 Hz and 7-25 Hz). We quantified the amount of power in each bandwidth. From 25 eligible participants, 10 PD participants (9 males, mean age 63.8 years) fulfilled the inclusion criteria; idiopathic PD responsive to l-Dopa; >1 year use of bilateral STN stimulation. Seventeen controls (9 males, mean age 71.2 years) were studied for comparison. Participants with PD were assessed after overnight withdrawal of anti-PD medications. Postural control was measured with a force platform during quiet stance (35 s) and during PRBS calf muscle vibration that perturbed stance (200 s). Tests were performed with eyes open and eyes closed and with DBS ON and DBS OFF. The balance perturbation period was divided into five sequential 35-s periods to assess the subject's ability to address postural imbalance using adaptation. The signal processing analyses revealed that DBS did not significantly change the dynamics of postural control in the 0-4 Hz spectral power but the device reduced the use of spectral power >4 Hz; a finding that was present in both anteroposterior and lateral directions, during vibration, and more so in eyes open tests. Visual feedback, which usually improves postural stability, was less effective in participants with PD with DBS OFF across all postural sway frequencies during quiet stance and during balance perturbations. The expected adaptation of postural control was found in healthy participants between the first and last balance perturbation period. However, adaptation was almost abolished across all spectral frequencies in both the anteroposterior and lateral directions, with both eyes open and eyes closed and DBS ON and OFF in participants with PD. To conclude, this study revealed that DBS altered the spectral frequency dynamics of postural control in participants through a reduction of the power used >4 Hz. Moreover, DBS tended to increase the stabilizing effect of vision across all spectral bands. However, the signal processing analyses also revealed that DBS was not able to restore adaptive motor control abilities in PD.


Asunto(s)
Estimulación Encefálica Profunda , Enfermedad de Parkinson , Anciano , Humanos , Levodopa/uso terapéutico , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/terapia , Equilibrio Postural , Temblor
10.
J Vestib Res ; 17(1): 47-62, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-18219104

RESUMEN

Control of orthograde posture and use of adaptive adjustments constitutes essential topics of human movement control, both in maintenance of static posture and in ensuring body stability during locomotion. The objective was to investigate, in twelve normal subjects, how head, shoulder, hip and knee movements and torques induced towards the support surface were affected by vibratory proprioceptive and galvanic vestibular stimulation, and to investigate whether movement pattern, body posture and movement coordination were changed over time. Our findings suggest that the adaptive process to enhance stability involves both alteration of the multi-segmented movement pattern and alteration of body posture. The magnitude of the vibratory stimulation intensity had a prominent influence on the evoked multi-segmented movement pattern. The trial conditions also influenced whether the posture were altered and if these posture adjustments were done directly at stimulation onset or gradually over a longer period. Moreover, the correlation values showed that the subjects, primarily during trials with vibratory stimulation alone, significantly increased the body movement coordination at stimulation onset and maintained this movement pattern throughout the stimulation period. Furthermore, when exposed to balance perturbations the test subjects synchronized significantly the head and torso movements in anteroposterior direction during all trial conditions.


Asunto(s)
Movimiento/fisiología , Postura/fisiología , Propiocepción/fisiología , Desempeño Psicomotor/fisiología , Vestíbulo del Laberinto/fisiología , Vibración , Adaptación Fisiológica , Adulto , Estimulación Eléctrica , Femenino , Humanos , Masculino , Orientación/fisiología , Valores de Referencia , Estadísticas no Paramétricas
11.
J Med Chem ; 47(16): 3927-30, 2004 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-15267230

RESUMEN

The understanding of the physiological role of the G-protein coupled serotonin 5-HT(7) receptor is largely rudimentary. Therefore, selective and potent pharmacological tools will add to the understanding of serotonergic effects mediated through this receptor. In this report, we describe two compound classes, chromans and tetralins, encompassing compounds with nanomolar affinity for the 5-HT(7) receptor and with good selectivity. Within theses classes, we have discovered both agonists and antagonists that can be used for further understanding of the pharmacology of the 5-HT(7) receptor.


Asunto(s)
Cromanos/síntesis química , Receptores de Serotonina/efectos de los fármacos , Antagonistas de la Serotonina/síntesis química , Agonistas de Receptores de Serotonina/síntesis química , Tetrahidronaftalenos/síntesis química , Animales , Células CHO , Cromanos/química , Cromanos/farmacología , Cricetinae , AMP Cíclico/biosíntesis , Ligandos , Receptores de Serotonina/metabolismo , Antagonistas de la Serotonina/química , Antagonistas de la Serotonina/farmacología , Agonistas de Receptores de Serotonina/química , Agonistas de Receptores de Serotonina/farmacología , Estereoisomerismo , Relación Estructura-Actividad , Tetrahidronaftalenos/química , Tetrahidronaftalenos/farmacología
12.
IEEE Trans Biomed Eng ; 50(12): 1310-9, 2003 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-14656060

RESUMEN

The objective for this study was to investigate whether the adaptation of postural control was similar during galvanic vestibular stimulation and during vibratory proprioceptive stimulation of the calf muscles. Healthy subjects were tested during erect stance with eyes open or closed. An analysis method designed to consider the adaptive adjustments was used to evaluate the motion dynamics and the evoked changes of posture and stimulation response. Galvanic vestibular stimulation induced primarily lateral body movements and vibratory proprioceptive stimulation induced anteroposterior movements. The lateral body sway generated by the galvanic stimulation was proportionally smaller and contained more high-frequency movements (> 0.1 Hz) than the anteroposterior body sway induced by the vibratory stimulation. The adaptive adjustments of the body sway to the stimulation had similar time course and magnitude during galvanic and vibratory stimulation. The perturbations induced by stimulation were gradually reduced within the same time range (15-20 s) and both kinds of stimulation induced a body leaning whose direction was dependent on stimulus. The similarities in the adjustment patterns suggest that postural control operates in the same way independent of the receptor systems affected by the disturbance and irrespective of whether the motion responses were induced in a lateral or anteroposterior direction.


Asunto(s)
Estimulación Eléctrica , Modelos Biológicos , Movimiento/fisiología , Equilibrio Postural/fisiología , Postura/fisiología , Propiocepción/fisiología , Nervio Vestibular/fisiología , Adaptación Fisiológica/fisiología , Adulto , Simulación por Computador , Retroalimentación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estimulación Física/métodos , Vibración , Percepción Visual/fisiología
13.
Scand J Work Environ Health ; 29(2): 152-8, 2003 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-12718501

RESUMEN

OBJECTIVES: The composition of thermal degradation products from two types of polyurethane foams, one based on toluene diisocyanate (TDI) and the other on diphenylmethane diisocyanate (MDI), was analyzed and their toxic lung effects were compared. METHODS: Isolated perfused lungs of guinea pig were subjected to thermal decomposition products of polyurethane foams from an aerosol generator with compartments for diluting, mixing, and sampling. RESULTS: Thermal degradation of MDI-based polyurethane foams released MDI, phenyl isocyanate, and methyl isocyanate. The emitted particulate fraction was 75% for MDI, whereas that for TDI from TDI-based polyurethane foam was 3%. Thermal degradation products from MDI-based foam caused a pronounced dose-dependent decrease in the measured lung function parameters (conductance and compliance). In contrast, the thermal degradation products from TDI-based foam did not cause any decrease in lung function. CONCLUSIONS: Thermal degradation products generated from MDI-based polyurethane foam were more toxic to the lung than those generated from TDI-based polyurethane foam. This difference was probable due to MDI in the particle phase.


Asunto(s)
Isocianatos/farmacología , Pulmón/fisiopatología , Poliuretanos/efectos adversos , 2,4-Diisocianato de Tolueno/farmacología , Aerosoles , Contaminantes Ocupacionales del Aire/efectos adversos , Animales , Industria Química , Modelos Animales de Enfermedad , Monitoreo del Ambiente , Femenino , Cobayas , Calor , Isocianatos/efectos adversos , Masculino , Perfusión , Probabilidad , Medición de Riesgo , 2,4-Diisocianato de Tolueno/efectos adversos
14.
J Med Chem ; 56(8): 3177-90, 2013 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-23516963

RESUMEN

We have developed two parallel series, A and B, of CX3CR1 antagonists for the treatment of multiple sclerosis. By modifying the substituents on the 7-amino-5-thio-thiazolo[4,5-d]pyrimidine core structure, we were able to achieve compounds with high selectivity for CX3CR1 over the closely related CXCR2 receptor. The structure-activity relationships showed that a leucinol moiety attached to the core-structure in the 7-position together with α-methyl branched benzyl derivatives in the 5-position displayed promising affinity, and selectivity as well as physicochemical properties, as exemplified by compounds 18a and 24h. We show the preparation of the first potent and selective orally available CX3CR1 antagonists.


Asunto(s)
Esclerosis Múltiple/tratamiento farmacológico , Pirimidinas/farmacología , Receptores de Quimiocina/antagonistas & inhibidores , Tiazoles/farmacología , Amino Alcoholes/síntesis química , Amino Alcoholes/farmacocinética , Amino Alcoholes/farmacología , Animales , Receptor 1 de Quimiocinas CX3C , Células CACO-2 , Humanos , Pirimidinas/síntesis química , Pirimidinas/química , Pirimidinas/farmacocinética , Ratas , Relación Estructura-Actividad , Tiazoles/síntesis química , Tiazoles/química , Tiazoles/farmacocinética
16.
J Physiol Paris ; 103(3-5): 159-77, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19671443

RESUMEN

This paper presents a theoretical model of stability and coordination of posture and locomotion, together with algorithms for continuous-time quadratic optimization of motion control. Explicit solutions to the Hamilton-Jacobi equation for optimal control of rigid-body motion are obtained by solving an algebraic matrix equation. The stability is investigated with Lyapunov function theory and it is shown that global asymptotic stability holds. It is also shown how optimal control and adaptive control may act in concert in the case of unknown or uncertain system parameters. The solution describes motion strategies of minimum effort and variance. The proposed optimal control is formulated to be suitable as a posture and movement model for experimental validation and verification. The combination of adaptive and optimal control makes this algorithm a candidate for coordination and control of functional neuromuscular stimulation as well as of prostheses. Validation examples with experimental data are provided.


Asunto(s)
Modelos Biológicos , Movimiento/fisiología , Equilibrio Postural/fisiología , Postura/fisiología , Desempeño Psicomotor/fisiología , Adaptación Fisiológica/fisiología , Algoritmos , Simulación por Computador , Retroalimentación Fisiológica , Humanos , Dinámicas no Lineales , Procesamiento de Señales Asistido por Computador , Factores de Tiempo
17.
Artículo en Inglés | MEDLINE | ID: mdl-18002378

RESUMEN

A new algorithm, based on embedding phase space, to detect the P-wave characteristic points of an ECG signal is reported in this paper. The multi-lead ECG is transformed into points of an embedding phase space where similar ECG morphologies are converted into phase space points that are close using some distance measure. The algorithm is robust with respect to the type of selected characteristic points (onset, peak and end), morphology changes, baseline oscillations and high frequency noise. The performance of the algorithm has been successfully validated using both simulated and real ECG signals.


Asunto(s)
Electrocardiografía/instrumentación , Electrocardiografía/métodos , Procesamiento de Señales Asistido por Computador , Algoritmos , Artefactos , Automatización , Calibración , Simulación por Computador , Procesamiento Automatizado de Datos , Sistema de Conducción Cardíaco , Humanos , Modelos Estadísticos , Redes Neurales de la Computación , Reproducibilidad de los Resultados , Técnica de Sustracción , Factores de Tiempo
18.
Int J Med Robot ; 2(1): 21-7, 2006 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17520610

RESUMEN

BACKGROUND: During 20 years of development of catheter-based technologies in the management of cardiac arrhythmias, electrophysiological mapping/ablation systems have evolved from single-plane fluoroscopic mapping to three-dimensional (3-D) non-fluoroscopic computer-based mapping systems. METHODS: Based on magnetic technology, the electro-anatomic CARTO mapping system can accurately correlate local electrograms with recording sites, by which the system can reconstruct 3-D maps with colour-coded electrophysiological information superimposed on the anatomy. Whereas the CARTO system is primarily designed for studying cardiac activation and not repolarisation, the system has been widely used in the diagnosis and ablation of cardiac arrhythmias and in the research of basic arrhythmic mechanisms. RESULTS: In order to study cardiac repolarisation in vivo, an innovative method, the monophasic action potential (MAP) mapping technique, which integrates MAP recording with electroanatomical mapping, has recently been developed in our centre. Using the MAP technique, global sequence and dispersion of atrial/ventricular repolarisation have been evaluated in vivo in both experimental and clinical settings. CONCLUSION: The innovative MAP technique provides unique research opportunities for in vivo studies of basic electrophysiological mechanisms.


Asunto(s)
Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/terapia , Cateterismo Cardíaco , Técnicas Electrofisiológicas Cardíacas , Potenciales de Acción , Cateterismo Cardíaco/instrumentación , Ablación por Catéter , Técnicas Electrofisiológicas Cardíacas/instrumentación , Humanos , Procesamiento de Imagen Asistido por Computador , Magnetismo
19.
Eur J Clin Pharmacol ; 62(1): 57-63, 2006 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-16372173

RESUMEN

BACKGROUND AND OBJECTIVES: Drug and Therapeutics Committees (DTCs), which are essential for ensuring the rational use of drugs (RUD) in hospitals, have recently been established in Laos. Sub-optimal performance had been reported. The aims of this study were to determine those factors in the working environment that relate to DTC performance in Lao hospitals and evaluate whether DTC performance could be improved through an educational intervention utilizing auditing and feedback targeted towards DTC members. METHODS: This was a quasi-experimental (before and after) study. Two central and seven provincial hospitals and the DTC members from these hospitals participated in the study. Performance of the DTCs was assessed by means of specifically developed indicators on structure and process combined with indicators for RUD and adherence to Standard Treatment Guidelines (STG). Data were collected for a 3-month period at baseline and for three consecutive periods thereafter. The results of the first three data collections were shared and discussed with the DTC members during feedback sessions. The DTC members were also interviewed in order to identify factors they thought may have an impact on DTC performance. RESULTS: Following the intervention, there was a significant improvement in the overall score for DTC performance (p<0.001) and, in particular, in general activity and feedback and drug information to staff. The STG scores also improved (p<0.01). Interviews indicated that one negative factor was the experience of the DTC members being overloaded with other work, resulting in DTC meetings being held irregularly and drawing poor attendance. CONCLUSION: Continuous self-monitoring of performance by means of indicators, followed by feedback discussions, is suggested the means of improving the work of the DTC.


Asunto(s)
Adhesión a Directriz/normas , Administración Hospitalaria/normas , Comité Farmacéutico y Terapéutico/organización & administración , Enfermedades Transmisibles/tratamiento farmacológico , Revisión de la Utilización de Medicamentos , Investigación sobre Servicios de Salud , Humanos , Laos , Indicadores de Calidad de la Atención de Salud/normas
20.
Europace ; 7 Suppl 2: 39-48, 2005 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-16102502

RESUMEN

AIMS: When analyzing P-wave morphology, the vectorcardiogram (VCG) has been shown useful to identify indicators of propensity to atrial fibrillation (AF). Since VCG is rarely used in the clinical routine, we wanted to investigate if these indicators could be accurately determined in VCG derived from standard 12-lead ECG (dVCG). METHODS: ECG and VCG recordings from 21 healthy subjects and 20 patients with a history of AF were studied. dVCG was calculated from ECG using the inverse Dower transform. Following signal averaging of P-waves, comparisons were made between VCG and dVCG, where three parameters characterizing signal shape and 15 parameters describing the P-wave morphology were used to assess the compatibility of the two recording techniques. The latter parameters were also used to compare the healthy and the AF groups. RESULTS: After transformation, P-wave shape was convincingly preserved. P-wave morphology parameters were consistent within the respective groups when comparing VCG and dVCG, with better preservation observed in the healthy group. CONCLUSION: VCG derived from routine 12-lead ECG may be a useful alternate method for studying orthogonal P-wave morphology.


Asunto(s)
Fibrilación Atrial/fisiopatología , Sistema de Conducción Cardíaco/fisiopatología , Vectorcardiografía , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Matemática , Persona de Mediana Edad , Procesamiento de Señales Asistido por Computador
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