[Effects of inspiratory muscle training on respiratory function and balance in stroke survivors: a randomized controlled trial]. / Efectos del entrenamiento muscular inspiratorio sobre la función respiratoria y el equilibrio en supervivientes de ictus: un ensayo clínico controlado aleatorizado.

INTRODUCTION: After a stroke, patients with hemiparesis and / or hemiplegia will present a notable asymmetry of the trunk and pelvis, and decreased postural stability and balance, affecting, consequently, respiratory function. OBJECTIVE: The objective of this study is to analyze the effects of inspiratory muscle training (IMT) on lung function, inspiratory muscle strength, postural and trunk control and balance in stroke survivors in the subacute phase. MATERIALS AND METHODS: 16 survivors of stroke in the subacute phase participated in RCT (experimental = 8; placebo = 8). The experimental group received IMT program, 5 days a week, once a day, for 8 weeks, with a progressive intensity from 15% to 60% of the PImax. The placebo group performed the same program, but with a fixed load of 7cmH20. Inspiratory muscle strength (PImax), lung function (FVC, FEV1, PEF, VMV), trunk control (TCT), and postural control and balance (PASS and Berg Scale) were evaluated. RESULTS: Experimental and placebo groups showed significant increases in PImax, with a difference between groups. There was a moderate and negative correlation between the initial PImax value and the percentage change (?PImax) (r = -0.572; p = 0.021). Significant increases in VMV (l/m) were observed in the experimental group, and increases in PASS in both groups, but without significant differences between groups. CONCLUSIONS: Inspiratory muscle training, although low intensity, is effective in improving inspiratory muscle strength in stroke survivors. However, the effects on postural control and balance remain uncertain.

TITLE: Efectos del entrenamiento muscular inspiratorio sobre la función respiratoria y el equilibrio en supervivientes de ictus: un ensayo clínico controlado aleatorizado.Introducción. Tras un ictus, los pacientes con hemiparesia y/o hemiplejía van a presentar una asimetría notable del tronco y la pelvis, y una disminución de la estabilidad postural y el equilibrio, lo que afecta, como consecuencia, a la función respiratoria. Objetivo. Analizar los efectos del entrenamiento muscular inspiratorio (EMI) sobre la función pulmonar, la fuerza muscular inspiratoria, el control postural y del tronco y el equilibrio en supervivientes de ictus. Materiales y métodos. Dieciséis pacientes supervivientes de ictus en fase subaguda participaron en un ensayo clínico controlado aleatorizado (experimental = 8; placebo = 8). El grupo experimental recibió un programa de EMI, cinco días a la semana, una vez al día, durante ocho semanas, con una intensidad progresiva del 15 al 60% de la PImáx. El grupo placebo realizó el mismo programa, pero con una carga fija de 7 cmH2O. Se evaluaron la fuerza muscular inspiratoria ­presión inspiratoria máxima (PImáx)­, la función pulmonar (capacidad vital forzada, volumen espirado en el primer segundo, flujo espiratorio máximo y ventilación voluntaria máxima), el control del tronco (test de control del tronco), y el control postural y el equilibrio ­Postural Scale for Stroke Patients (PASS) y escala de Berg­. Resultados. Los grupos experimental y placebo presentaron incrementos significativos en la PImáx, con diferencia entre grupos. Existió una correlación negativa y moderada entre el valor de la PImáx inicial y el porcentaje de cambio (?PImáx) (r = ­0,572; p = 0,021). Se observaron incrementos significativos en la ventilación voluntaria máxima (L/m) en el grupo experimental, e incrementos en la PASS en ambos grupos, pero sin diferencias significativas entre grupos. Conclusiones. El entrenamiento muscular inspiratorio, aunque de baja intensidad, es efectivo para mejorar la fuerza muscular inspiratoria en pacientes supervivientes de ictus. Sin embargo, los efectos sobre el control postural y el equilibrio permanecen inciertos.

[Analysis of the patient safety culture in hospitals of the Spanish National Health System]. / Análisis de la cultura sobre seguridad del paciente en los hospitales del Sistema Nacional de Salud español.

BACKGROUND AND OBJECTIVES: A safety culture is essential to minimize errors and adverse events. Its measurement is needed to design activities in order to improve it. This paper describes the methods and main results of a study on safety climate in a nation-wide representative sample of public hospitals of the Spanish NHS. MATERIAL AND METHOD: The Hospital Survey on Patient Safety Culture questionnaire was distributed to a random sample of health professionals in a representative sample of 24 hospitals, proportionally stratified by hospital size. Results are analyzed to provide a description of safety climate, its strengths and weaknesses. Differences by hospital size, type of health professional and service are analyzed using ANOVA. RESULTS: A total of 2503 responses are analyzed (response rate: 40%, (93% from professionals with direct patient contact). A total of 50% gave patient safety a score from 6 to 8 (on a 10-point scale); 95% reported < 2 events last year. Dimensions "Teamwork within hospital units" (71.8 [1.8]) and "Supervisor/Manager expectations and actions promoting safety" (61.8 [1.7]) have the highest percentage of positive answers. "Staffing", "Teamwork across hospital units", "Overall perceptions of safety" and "Hospital management support for patient safety" could be identified as weaknesses. Significant differences by hospital size, type of professional and service suggest a generally more positive attitude in small hospitals and Pharmacy services, and a more negative one in physicians. CONCLUSIONS: Strengths and weaknesses of the safety climate in the hospitals of the Spanish NHS have been identified and they are used to design appropriate strategies for improvement.

Colony-stimulating factors regulate the development of multinucleated osteoclasts from recently replicated cells in vitro.

Osteoclasts mediate the process of bone resorption. However, little is known about the mechanisms that regulate the formation of either osteoclasts or osteoclast precursors. In contrast, colony-stimulating factors (CSFs) are well-known to regulate the formation of myeloid cells and their precursors. Because osteoclasts and myeloid cells may originate from a common stem cell, we examined the effects of two CSFs, granulocyte-macrophage CSF (GM-CSF) and interleukin 3 (IL-3), on bone resorption, osteoclast formation, and the incorporation of recently replicated nuclei into the osteoclasts of mouse bone cultures. CSFs had little effect on the formation rate of osteoclasts or their resorptive activity but significantly decreased the percentage of recently replicated osteoclast progenitor cell nuclei present in the osteoclasts of bones treated with parathyroid hormone. GM-CSF also increased the number of myeloid cells in the marrow space of the cultures and the percentage of these cells derived from recently replicated progenitors. These results demonstrate that GM-CSF and IL-3 can regulate the development of osteoclasts from recently replicated precursor cells in cultured fetal mouse long bones. However, the mechanisms by which CSFs influence osteoclast formation are difficult to determine from these studies because markers for the osteoclast progenitor and precursor do not exist. These data also provide evidence that the differentiation of osteoclast progenitors is regulated by different factors at different points in their ontogeny.

Production of both interleukin-1 alpha and beta by newborn mouse calvarial cultures.

The conditioned medium (CM) from 4-6 day newborn mouse calvarial cultures was found to contain thymocyte comitogen proliferation activity. This activity was blocked by an antiserum to murine interleukin-1 alpha (IL-1 alpha) but not by an antiserum to murine interleukin-1 beta. The release of thymocyte comitogen proliferation activity from the cultures did not appear dependent on endotoxin and was not associated with detectable interleukin-2 activity in the CM. Activity in the CM eluted from a gel filtration column with a peak Mr of 16-18 kD (the Mr of mature murine IL-1 alpha and beta is 17 kD). Western immunoblots of 100-fold concentrated CM demonstrated only a single 33 kD band with an antiserum to murine IL-1 beta and no bands with an antiserum to murine IL-1 alpha. However, this assay was relatively insensitive (limit of detection 1-10 ng compared with 1-10 pg for the thymocyte comitogen proliferation assay). Immunoprecipitation of [35S]methionine-labeled CM with three different anti-IL-1 alpha antisera, a more sensitive assay, demonstrated 15-17 kD bands in all cases. These results demonstrate that 4-6 day newborn mouse calvarial cultures spontaneously release 17 kD IL-1 alpha and 33 kD IL-1 beta into their conditioned medium. It appears that although 17 kD IL-1 alpha is the major bioactive form in the CM, 33 kD IL-1 beta is present in greater amounts. These results also suggest that local production of IL-1 can regulate bone cell function and may play a role in bone growth and remodeling.

Interleukin-1 in combination with transforming growth factor-alpha produces enhanced bone resorption in vitro.

Interleukin-1 (IL-1) and transforming growth factor-alpha (TGF alpha) both stimulate bone resorption. We examined the effects that the combination of these two agents had on fetal rat long bone cultures. The 48-h resorptive response to recombinant human TGF alpha was markedly enhanced in the presence of IL-1 (either purified from stimulated human monocytes or recombinant human IL-1 alpha) compared to the effects of either agent alone. The enhanced resorptive response to the combination appeared to be dependent on prostaglandin (PG) synthesis, since it was associated with an increase in PGE concentrations in the medium and was completely blocked by either indomethacin or flufenamic acid. Substitution of TGF alpha with epidermal growth factor, a TGF alpha analog, produced identical results. We also found that IL-1 inhibited the mitogenic response of the cultures to TGF alpha. The effects of IL-1 and TGF alpha on PGE concentrations in the medium and DNA synthesis were similar in the osteoblast-like cell line MC3T3-E1. Activated macrophages and certain malignant cells are capable of producing both IL-1 and TGF alpha. Hence, similar interactions could occur in vivo and may regulate some of the effects that either immune or malignant cells have on bone.

Comparison of the bone-resorbing activity in the supernatants from phytohemagglutinin-stimulated human peripheral blood mononuclear cells with that of cytokines through the use of an antiserum to interleukin 1.

We compared the bone-resorbing activity in the conditioned medium from phytohemagglutinin (PHA)-stimulated human peripheral blood mononuclear cell cultures with that of partially purified human monocyte-derived interleukin 1 (IL-1), human recombinant IL-1 alpha (pI 5) and IL-1 beta (pI 7), human recombinant tumor necrosis factor-alpha (TNF alpha), and PTH in fetal rat long bone cultures. An antiserum to the products of activated human mononuclear cells, including IL-1, completely blocked the bone-resorbing activity of all three forms of IL-1 and of unfractionated PHA-stimulated human peripheral blood mononuclear cell supernatants, but did not inhibit resorption stimulated by recombinant human TNF alpha. This antiserum also had no effect on the resorptive response to 3 nM PTH, but did decrease the response to 1 nM PTH slightly. These results imply that IL-1, but not TNF alpha, mediates the bone-resorbing activity found in the supernatants of PHA-stimulated human peripheral blood mononuclear cell cultures. It is not known whether the small inhibitory effect that the antiserum to IL-1 had on the response to 1 nM PTH resulted from a nonspecific action or an effect of PTH on local IL-1 synthesis in bone. Since cytokines are found in the circulation of normal individuals and are produced at local sites of pathology, these results suggest that they can influence both normal and abnormal skeletal metabolism.

Leukemia inhibitory factor (LIF) inhibits basal bone resorption in fetal rat long bone cultures.

Leukemia inhibitory factor (LIF) has a wide variety of biologic actions. In vivo, its net effect on bone is to increase new bone formation. Recently, the sequence of human LIF was found to differ by only a single amino acid from that of human differentiation-inducing factor (D-factor). The effects of LIF on bone appear to be complex since purified murine D-factor and recombinant LIF stimulate bone resorption in cultured newborn mouse calvaria. To examine further the responses of bone to LIF, we studied the effects of recombinant human LIF (glycosylated and nonglycosylated) and recombinant human D-factor (non-glycosylated) on resorption in another in vitro organ culture model, fetal rat long bones. Both LIF preparations and D-factor inhibited basal bone resorption rates by 25% to 44% in these cultures. Resorption rates in maximally inhibited LIF-treated cultures were similar to those in devitalized bones. Inhibitory effects typically occurred at concentrations of greater than or equal to 10 ng/mL (0.5 nM) for the non-glycosylated LIF and D-factor and 1000 U/mL for glycosylated LIF. Neither LIF nor D-factor blocked the resorptive response to interleukin 1 (IL 1) or parathyroid hormone (PTH) nor did they alter total DNA synthesis. Hence, their inhibitory effects appeared to be specific for the mechanisms regulating basal resorptive activity. These results demonstrate that LIF has potent inhibitory actions on basal resorption rates in these cultures. These effects may be important for the anabolic responses that LIF has on bone in vivo. In addition, they may also be involved in the interactions between inflammatory or tumor cells and bone.

Contrasting synaptic actions of the inhalational general anesthetics isoflurane and xenon.

BACKGROUND: The mechanisms by which the inhalational general anesthetics isoflurane and xenon exert their effects are unknown. Moreover, there have been surprisingly few quantitative studies of the effects of these agents on central synapses, with virtually no information available regarding the actions of xenon. METHODS: The actions of isoflurane and xenon on gamma-aminobutyric acid-mediated (GABAergic) and glutamatergic synapses were investigated using voltage-clamp techniques on autaptic cultures of rat hippocampal neurons, a preparation that avoids the confounding effects of complex neuronal networks. RESULTS: Isoflurane exerts its greatest effects on GABAergic synapses, causing a marked increase in total charge transfer (by approximately 70% at minimum alveolar concentration) through the inhibitory postsynaptic current. This effect is entirely mediated by an increase in the slow component of the inhibitory postsynaptic current. At glutamatergic synapses, isoflurane has smaller effects, but it nonetheless significantly reduces the total charge transfer (by approximately 30% at minimum alveolar concentration) through the excitatory postsynaptic current, with the N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor-mediated components being roughly equally sensitive. Xenon has no measurable effect on GABAergic inhibitory postsynaptic currents or on currents evoked by exogenous application of GABA, but it substantially inhibits total charge transfer (by approximately 60% at minimum alveolar concentration) through the excitatory postsynaptic current. Xenon selectively inhibits the NMDA receptor-mediated component of the current but has little effect on the AMPA/kainate receptor-mediated component. CONCLUSIONS: For both isoflurane and xenon, the most important targets appear to be postsynaptic. The authors' results show that isoflurane and xenon have very different effects on GABAergic and glutamatergic synaptic transmission, and this may account for their differing pharmacologic profiles.