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Dopamine receptors have been claimed not to directly increase contractility in the human heart. Therefore, we performed contraction experiments in isolated electrically driven human atrial preparations (HAP). For comparison, we performed contraction experiments with left atrial preparations of transgenic mice which harbor a cardiac overexpression of human D1-dopamine receptors (D1-TG). In D1-TG, first we noted that dopamine (10 nM-10 µM cumulatively applied) in the presence of propranolol exerted a concentration- and time-dependent positive inotropic effect in D1-TG. In a similar fashion, dopamine increased force of contraction in the presence of 0.4 µM propranolol in HAP and these effects were amplified by pre-treatment with inhibitor of phosphodiesterase III (1 µM) cilostamide. Moreover, contractile effects of dopamine in the presence of propranolol 0.4 µM in HAP were antagonized by odapipam, haloperidol, or raclopride. Ten micromolars of fenoldopam in the presence of cilostamide increased force of contraction in HAP and this effect was antagonized by SCH 23390. We conclude that stimulation of human D1-dopamine receptors can increase force of contraction in the HAP.
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MR33317 was synthesized as an acetylcholinesterase-inhibitor and an agonist at brain 5-HT4-receptors. MR33317 might be used to treat Morbus Alzheimer. This therapeutic action of MR33317 might be based on MR33317´s dual synergistic activity. We tested the hypothesis that MR33317 also stimulates 5-HT4-receptors in the heart. MR33317 (starting at 10 nM) increased force of contraction and beating rate in isolated atrial preparations from mice with cardiac confined overexpression of the human 5-HT4-serotonin receptor (5-HT4-TG) but was inactive in wild type mouse hearts (WT). Only in the presence of the phosphodiesterase III-inhibitor cilostamide, MR33317 raised force of contraction under isometric conditions in isolated paced (1 Hz) human right atrial preparations (HAP). This increase in force of contraction in human atrium by MR33317 was attenuated by 10 µM tropisetron or GR125487. These data suggest that MR33317 is an agonist at human 5-HT4-serotonin receptors in the human atrium. Clinically, one would predict that MR33317 may lead to atrial fibrillation.
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Globodera ellingtonae was originally described from populations collected in the United States. In the original description, ribosomal DNA loci from Globodera sp. collected in Chile and Argentina were similar to G. ellingtonae, suggesting this nematode originated in this region of South America. In an effort to find additional populations of G. elllingtonae, collection trips were conducted in 2017 and 2020 in the Antofagasta and Arica y Parinacota Regions in Northern Chile, respectively. Globodera sp. were more prevalent in Antofagasta (17 samples collected, 53% positive for Globodera sp.) than in Arica y Parincota (16 samples collected, 13% positive for Globodera sp.). The genomes of single cysts (N ≥ 3) from four fields were sequenced. Additionally, the genomes of the G. ellingtonae population from Oregon and a Globodera sp. population originally collected in Antofagasta Region but maintained in culture in France were also sequenced. Based upon a HSP90 sequenced data mined from WSG data, all of the populations from the Antofagasta Region were G. ellingtonae and grouped in a monophyletic clade. A population collected from the Arica y Parincota Region was identified as G. rostochiensis based upon HSP90 data. Genome-wide SNP patterns of the G. ellingtonae populations showed strong clustering based on geographic location indicating that G. ellingtonae has high genetic diversity within Chile. A phylogenetic tree derived from 168,354 binary SNPs in the nuclear genome showed separate but distinct clustering of the Oregon population and the population from Antofagasta maintained in France. The Oregon G. ellingtonae population subtended the Chilean clades and placed on a long branch representing approximately twice the genetic variation observed among all Chilean G. ellingtonae populations. The possibility remains that G. ellingtonae from Chile may be sufficiently diverged to constitute a new species from G. ellingtonae originally described from a population collected in Oregon.
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BACKGROUND: Treatment with P2Y12 receptor antagonists increases the risk for perioperative bleeding, but there is individual variation in the antiplatelet effect and time to offset of this effect. We investigated whether preoperative platelet function predicts the risk of bleeding complications in ticagrelor-treated cardiac surgery patients. METHODS: Ninety patients with ticagrelor treatment within <5 days of surgery were included in a prospective observational study. Preoperative platelet aggregation was assessed with impedance aggregometry using adenosine diphosphate (ADP), arachidonic acid (AA), and thrombin receptor-activating peptide (TRAP) as initiators. Severe bleeding complications were registered using a new universal definition of perioperative bleeding. The accuracy of aggregability tests for predicting severe bleeding was assessed using receiver operating characteristic (ROC) curves, which also identified optimal cut-off values with respect to sensitivity and specificity, based on Youden's index. RESULTS: The median time from the last ticagrelor dose to surgery was 35 (range 4-108) h. The accuracy of platelet function tests to predict severe bleeding was highest for ADP [area under the ROC curve 0.73 (95% confidence interval 0.63-0.84, P<0.001); TRAP 0.61 (0.49-0.74); AA 0.53 (0.40-0.66)]. The optimal cut-off for ADP-induced aggregation was 22 U. In subjects with ADP-induced aggregation below the cut-off value, 24/38 (61%) developed severe bleeding compared with 8/52 (14%) when aggregation was at or above the cut-off value (P<0.001). The positive and negative predictive values for this cut-off value were 63 and 85%, respectively. CONCLUSIONS: Preoperative ADP-induced platelet aggregability predicts the risk for severe bleeding complications in ticagrelor-treated cardiac surgery patients.
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Adenosina/análogos & derivados , Plaquetas/fisiología , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Hemorragia Posoperatoria/etiología , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Adenosina/efectos adversos , Adenosina Difosfato/farmacología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Agregación Plaquetaria/efectos de los fármacos , Transfusión de Plaquetas , Estudios Prospectivos , TicagrelorRESUMEN
BACKGROUND: Transfusion of platelet concentrate is often used to treat bleeding in patients on platelet inhibitors, but little is known about its efficacy between different inhibitors. We assessed the effect of ex vivo platelet supplementation on platelet aggregability in blood samples from patients treated with acetylsalicylic acid (ASA), clopidogrel, or ticagrelor. METHODS: Platelet aggregability was investigated with multiple electrode aggregometry with adenosine diphosphate (ADP), arachidonic acid (to assess ASA-dependent aggregability), and thrombin receptor activating peptide-6 (TRAP) as activators in whole-blood samples from patients treated with ASA (n=10), ASA+clopidogrel (n=15), or ASA+ticagrelor (n=15), and from healthy controls (n=10). Aggregability was measured before and after supplementation of AB0-compatible fresh apheresis platelets (+46, +92, and +138×10(9) litre(-1)). RESULTS: Both ASA-dependent and ADP-dependent aggregability improved in a dose-dependent fashion after platelet supplementation. ASA-dependent aggregability was completely restored in all patient groups, but there was only a small improvement in ADP-dependent aggregability in patients on dual antiplatelet therapy. There was less effect of platelet supplementation on ADP- and ASA-dependent aggregability in ticagrelor-treated patients than in clopidogrel-treated patients [3.9 (95% confidence interval 1.6-6.3) vs 9.0 (5.2-12.8) AU×min (P=0.021) and 48 (36-59) vs 69 (60-78) AU×min (P=0.004), respectively, at the highest platelet dose]. CONCLUSIONS: Platelet supplementation improved platelet aggregability independently of antiplatelet therapy. The effect on ADP-dependent platelet inhibition was limited however. Reduced effect of platelet transfusion is more likely within 2 h of drug intake in patients treated with ASA+ticagrelor compared with ASA+clopidogrel.
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Adenosina/análogos & derivados , Aspirina/farmacología , Inhibidores de Agregación Plaquetaria/farmacología , Agregación Plaquetaria/efectos de los fármacos , Agregación Plaquetaria/fisiología , Transfusión de Plaquetas , Ticlopidina/análogos & derivados , Adenosina/farmacología , Adenosina Difosfato , Anciano , Ácido Araquidónico/farmacología , Clopidogrel , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fragmentos de Péptidos/farmacología , Ticagrelor , Ticlopidina/farmacologíaRESUMEN
A major concept in autoimmunity is that disruption of Foxp3(+) regulatory T cells (Tregs) predisposes to breach of tolerance. This is exemplified by the Foxp3-linked disorder termed IPEX (immunodysregulation, polyendocrinopathy, enteropathy, X-linked) which affects newborn children. There has been considerable clinical interest in the role of non-depleting anti-CD4 antibodies as a means of upregulating the function of Foxp3(+) Tregs in order to control detrimental inflammatory responses such as transplant rejection. However, according to the paradigm of a Treg-dependent mechanism of action, the effectiveness of anti-CD4 antibodies as a therapy for human autoimmune diseases is unclear considering that Treg function might be intrinsically impaired. Specifically, anti-CD4 therapy is expected to fail in patients suffering from the IPEX syndrome due to the lack of functional Foxp3(+) Tregs. Taking advantage of natural Foxp3 mutant scurfy (sf) mice closely resembling the IPEX syndrome, and genetically engineered mice depleted of Foxp3(+) Tregs, we report here that anti-CD4 treatment induces tolerance independent of Foxp3(+) Tregs. This so far undefined mechanism is dependent on the recessive non-infectious tolerization of autoreactive T cells. Treg-independent tolerance alone is powerful enough to suppress both the onset and severity of autoimmunity and reduces clinically relevant autoantibody levels and liver fibrosis. Mechanistically, tolerance induction requires the concomitant activation of autoreactive T cells and is associated with the down-regulation of the co-stimulatory TNF-receptor superfamily members OX40 and CD30 sustaining CD4(+) T cell survival. In the light of ongoing clinical trials, our results highlight an unexpected potency of anti-CD4 antibodies for the treatment of autoimmune diseases. Particularly, CD4 blockade might represent a novel therapeutic option for the human IPEX syndrome.
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Suero Antilinfocítico/farmacología , Autoinmunidad/efectos de los fármacos , Antígenos CD4/inmunología , Factores de Transcripción Forkhead/inmunología , Animales , Antígenos CD4/genética , Supervivencia Celular , Diabetes Mellitus Tipo 1/congénito , Diarrea , Modelos Animales de Enfermedad , Femenino , Factores de Transcripción Forkhead/deficiencia , Factores de Transcripción Forkhead/genética , Regulación de la Expresión Génica/inmunología , Enfermedades Genéticas Ligadas al Cromosoma X/tratamiento farmacológico , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Genéticas Ligadas al Cromosoma X/inmunología , Enfermedades Genéticas Ligadas al Cromosoma X/patología , Humanos , Enfermedades del Sistema Inmune/congénito , Tolerancia Inmunológica/efectos de los fármacos , Antígeno Ki-1/genética , Antígeno Ki-1/inmunología , Activación de Linfocitos , Masculino , Ratones , Ratones Transgénicos , Receptores OX40/genética , Receptores OX40/inmunología , Transducción de Señal , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/patologíaRESUMEN
We tested whether a delay between stimulus presentation and grasping leads to a shift from dorsal to ventral control of the movement, as suggested by the perception-action theory of Milner and Goodale (Milner, A.D., & Goodale, M.A. (1995). The visual brain in action. Oxford: Oxford University Press.). In this theory the dorsal cortical stream has a short memory, such that after a few seconds the dorsal information is decayed and the action is guided by the ventral stream. Accordingly, grasping should become responsive to certain visual illusions after a delay (because only the ventral stream is assumed to be deceived by these illusions). We used the Müller-Lyer illusion, the typical illusion in this area of research, and replicated the increase of the motor illusion after a delay. However, we found that this increase is not due to memory demands but to the availability of visual feedback during movement execution which leads to online corrections of the movement. Because such online corrections are to be expected if the movement is guided by one single representation of object size, we conclude that there is no evidence for a shift from dorsal to ventral control in delayed grasping of the Müller-Lyer illusion. We also performed the first empirical test of a critique Goodale (Goodale, M.A. (2006, October 27). Visual duplicity: Action without perception in the human visual system. The XIV. Kanizsa lecture, Triest, Italy.) raised against studies finding illusion effects in grasping: Goodale argued that these studies used methods that lead to unnatural grasping which is guided by the ventral stream. Therefore, these studies might never have measured the dorsal stream, but always the ventral stream. We found clear evidence against this conjecture.
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Lateralidad Funcional/fisiología , Fuerza de la Mano/fisiología , Ilusiones/fisiología , Memoria/fisiología , Tiempo de Reacción/fisiología , Vías Visuales/fisiología , Adolescente , Adulto , Análisis de Varianza , Retroalimentación/fisiología , Femenino , Humanos , Masculino , Reconocimiento Visual de Modelos/fisiología , Adulto JovenRESUMEN
The purpose of this study was to compare ganglionic blockade with trimethaphan (TMP) and an alternative drug strategy using combined muscarinic antagonist (glycopyrrolate, GLY) and alpha-2 agonist (dexmedetomidine, DEX). Protocol 1: incremental phenylephrine was administered during control and combined GLY-DEX, or control and TMP on two control combined GLY and DEX or TMP infusion on two randomized days. Protocol 2: muscle sympathetic nerve activity (MSNA) and the baroreflex MSNA relationship was determined before and after GLY-DEX. Blood pressure was higher with GLY-DEX (99+/-3 mm Hg) and lower with TMP (78+/-3 mm Hg) relative to control (GLY-DEX: 90+/-2 mm Hg; TMP: 91+/-2 mm Hg; P<0.05). Incremental phenylephrine increased pressure during GLY-DEX (P<0.01 vs control) and TMP (P<0.01 vs control) to a similar degree. Both GLY-DEX and TMP infusion inhibited norepinephrine release (P<0.01 vs control). GLY-DEX inhibited baseline MSNA (P<0.05) and baroreflex changes in MSNA (P<0.01). We conclude that the GLY-DEX alternative drug strategy can be used as a reasonable alternative to pharmacologic ganglionic blockade to examine autonomic cardiovascular control.
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Sistema Cardiovascular/efectos de los fármacos , Dexmedetomidina/administración & dosificación , Bloqueadores Ganglionares/administración & dosificación , Glicopirrolato/administración & dosificación , Trimetafan/administración & dosificación , Agonistas alfa-Adrenérgicos/administración & dosificación , Adulto , Bloqueo Nervioso Autónomo/métodos , Barorreflejo/efectos de los fármacos , Barorreflejo/fisiología , Gasto Cardíaco/efectos de los fármacos , Sistema Cardiovascular/inervación , Catecolaminas/metabolismo , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Antagonistas Muscarínicos/administración & dosificación , Fenilefrina/administración & dosificación , Sistema Nervioso Simpático/efectos de los fármacosRESUMEN
Genetic variation in drug targets (e.g. receptors) can have pronounced effects on clinical responses to endogenous and exogenous agonists. Polymorphisms in the gene encoding the ß(2)-adrenergic receptor (ß(2)-AR) have been associated with altered expression, down-regulation, and altered cell signaling in vitro. Because ß(2)-ARs play a crucial role in the regulation of the cardiovascular system, the functional importance of genetic variation in the ß(2)-AR on cardiovascular responses to physiological or pharmacological stimuli has gained widespread attention. The objective of this review is to characterize these intermediate cardiovascular phenotypes and their influence on cardiovascular disease and adrenergic drug responses.Two common single nucleotide polymorphisms, encoded at codon 46 (Gly(16)Arg) and 79 (Gln(27)Glu) of the ß(2)-AR gene, have been studied intensively. They have been shown to be associated with altered vasodilator responses to regional and systemic administration of ß(2)-agonists, altered cardiovascular responses to sympathoexcitatory maneuvers, and altered myocardial function. Importantly, these intermediate physiological patterns may influence the development of and the outcomes associated with hypertension and other cardiovascular diseases. As recently reported, ß(2)-AR gene variation can risk-stratify patients receiving ß-blocker therapy and may predict ß-blocker efficacy in patients post acute coronary syndrome or in patients with heart failure.Further studies will advance our understanding of the link between ß(2)-AR genotypes, intermediate cardiovascular phenotypes, and clinical phenotypes. In the long term, reassessment of the benefits of ß-blocker-therapy within genotype groups should be carried out with the ultimate goal to design the optimal therapeutic regimen for the individual patient.
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Conventional methods for monitoring clinical (epileptiform) multichannel electroencephalogram (EEG) signals often involve morphological, spectral or time-frequency analysis on individual channels to determine waveform features for detecting and classifying ictal events (seizures) and inter-ictal spikes. Blind source separation (BSS) methods, such as independent component analysis (ICA), are increasingly being used in biomedical signal processing and EEG analysis for extracting a set of underlying source waveforms and sensor projections from multivariate time-series data, some of which reflect clinically relevant neurophysiological (epileptiform) activity. The work presents an alternative spatial approach to source tracking and detection in multichannel EEG that exploits prior knowledge of the spatial topographies of the sensor projections associated with the target sources. The target source sensor projections are obtained by ICA decomposition of data segments containing representative examples of target source activity, e.g. a seizure or ocular artifact. Source tracking and detection are then based on the subspace correlation between individual target sensor projections and the signal subspace over a moving window. Different window lengths and subspace correlation threshold criteria reflect transient or sustained target source activity. To study the behaviour and potential application of this spatial source tracking and detection approach, the method was used to detect (transient) ocular artifacts and (sustained) seizure activity in two segments of 25-channel EEG data recorded from one epilepsy patient on two separate occasions, with promising and intuitive results.
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Electroencefalografía/métodos , Epilepsia/diagnóstico , Interpretación de Imagen Asistida por Computador , Procesamiento de Señales Asistido por Computador , Humanos , Cuero CabelludoRESUMEN
This contribution addresses two different areas of the complex relationship between pharmacotherapy and sexual function and dysfunction in men and women. As many impairments of sexual function are caused by side effects of medications, particularly psychotropic drugs, the first part of the paper describes substances and mechanisms often related to sexual dysfunction with a special focus on antidepressants and neuroleptics. While serotonin reuptake inhibitors entail a high risk of sexual dysfunction, it is often difficult to differentiate the negative impact of the drug from the impairment caused by the mental disorder itself. Ways to deal with these dysfunctions and remedial measures are discussed. In the second section, current pharmacological treatments for female and male sexual dysfunctions are reviewed. While there is no approved pharmacotherapy with established efficacy for female sexual dysfunction with the possible exception of the transdermal testosterone patch for surgically menopausal women, effective pharmacological therapies are available for male erectile disorders. In addition, testosterone substitution is the treatment of choice for hypoactive sexual desire disorders caused by hypogonadism. As sexual dysfunctions are often caused by a mixture of psychological and organic factors, treatment strategies combining pharmacological options and sex therapy are advocated.
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Hormonas/uso terapéutico , Psicotrópicos/efectos adversos , Consejo Sexual/métodos , Disfunciones Sexuales Fisiológicas/inducido químicamente , Disfunciones Sexuales Fisiológicas/terapia , Disfunciones Sexuales Psicológicas/inducido químicamente , Disfunciones Sexuales Psicológicas/terapia , Sexualidad/efectos de los fármacos , Terapia Combinada , Humanos , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina , Resultado del TratamientoRESUMEN
Conventional methods for monitoring clinical (epileptiform) multichannel electroencephalogram (EEG) signals often involve morphological, spectral or time-frequency analysis on individual channels to determine waveform features for detecting and classifying ictal events (seizures) and inter-ictal spikes. Blind source separation (BSS) methods, such as independent component analysis (ICA), are increasingly being used in biomedical signal processing and EEG analysis for extracting a set of underlying source waveforms and sensor projections from multivariate time-series data, some of which reflect clinically relevant neurophysiological (epileptiform) activity. The work presents an alternative spatial approach to source tracking and detection in multichannel EEG that exploits prior knowledge of the spatial topographies of the sensor projections associated with the target sources. The target source sensor projections are obtained by ICA decomposition of data segments containing representative examples of target source activity, e.g. a seizure or ocular artifact. Source tracking and detection are then based on the subspace correlation between individual target sensor projections and the signal subspace over a moving window. Different window lengths and subspace correlation threshold criteria reflect transient or sustained target source activity. To study the behaviour and potential application of this spatial source tracking and detection approach, the method was used to detect (transient) ocular artifacts and (sustained) seizure activity in two segments of 25-channel EEG data recorded from one epilepsy patient on two separate occasions, with promising and intuitive results.
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Electroencefalografía/métodos , Epilepsia/diagnóstico , Procesamiento de Señales Asistido por Computador , Artefactos , HumanosRESUMEN
Within a dynamical embedding (DE) framework it is possible to extract information on multiple-sources underlying just a single channel recording of electromagnetic brain activity. Independent Component Analysis (ICA) is a technique which, when used in conjunction with DE, can identify and extract statistically independent sources underlying these single channel recordings. However, these powerful techniques still generally require subjective a posteriori analysis in order to visualise neurophysiologically meaningful components in the outputs. For this reason we introduce a variant of ICA known as constrained ICA (cICA) which allows for the extraction of one of many sources underlying the measurement signal, through the provision of a basic reference signal. This constraint can be chosen to reflect neurophysiological prior knowledge of the sources in question given the measured signal. Here we present a technique which allows for the application of spectral constraints on single channel recordings of epileptic EEG data. We show that through a combination of DE and cICA it is possible to extract meaningful information on epileptic seizures and other rhythmic activity from just a single channel of EEG. We further show that accurate extraction of the sources of interest is not critically dependent on the closeness of the measurement channel to the location of the source activity.
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Pharmacological approaches for the treatment of cardioinhibitory vasovagal syncope are controversially discussed in the literature. In acute treatment of neurocardiogenic syncope, anticholinergics (atropine) are used effectively. Randomised and placebo-controlled clinical trials evaluating the preventive significance of anticholinergic agents in the therapy of cardioinhibitory vasovagal syncope are still missing. We report the case of an 18-year-old male patient with recurrent convulsive, cardioinhibitory neurocardiogenic syncope. Vasovagal syncope occurred predominantly as centrally induced syncope triggered by negative emotions such as fear or by seeing blood. Under resting conditions, the patient revealed increased parasympathetic tone with nocturnal bradycardia of 38 beats/min. In the course of head-up tilt table testing a cardioinhibitory syncope with an asystolic pause of 10 seconds occurred without any prodromes after 10 minutes of upright positioning. In order to inhibit parasympathetic tone, medication with ipratropiumbromide was initiated. Time-variant analysis of heart rate variability (autoregressive model) during head-up tilt table testing showed under the medication with ipratropiumbromide a vagal mediated cardioinhibition to 56 beats/min, but no further sinus arrest. Throughout clinical follow-up of 6 months the patient remained syncope-free under the medication. The usefulness of ipratropiumbromide in inhibiting vagal mediated cardioinhibition will be discussed referring to the case report and to studies evaluating anticholinergic agents in the treatment of neurocardiogenic syncope.
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Antagonistas Colinérgicos/uso terapéutico , Ipratropio/uso terapéutico , Síncope Vasovagal/tratamiento farmacológico , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Manejo de Atención al Paciente/métodos , Recurrencia , Resultado del TratamientoRESUMEN
After a period of eccentric exercise of elbow flexor muscles of one arm in young, adult human subjects, muscles became fatigued and damaged. Damage indicators were a fall in force, change in resting elbow angle and delayed onset of soreness. After the exercise, subjects were asked to match the forearm angle of one arm, whose position was set by the experimenter, with their other arm. Subjects matched the position of the unsupported reference arm, when this was unexercised, with a significantly more flexed position in their exercised indicator arm. Errors were in the opposite direction when the reference arm was exercised. The size of the errors correlated with the drop in force. Less consistent errors were observed when the reference arm was supported. A similar pattern of errors was seen after concentric exercise, which does not produce muscle damage. The data suggested that subjects were using as a position cue the perceived effort required to maintain a given forearm angle against the force of gravity. The fall in force from fatigue after exercise meant more effort was required to maintain a given position. That led to matching errors between the exercised and unexercised arms. It was concluded that while a role for muscle spindles in kinaesthesia cannot be excluded, detailed information about static limb position can be derived from the effort required to support the limb against the force of gravity.
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Articulación del Codo/fisiología , Fatiga Muscular/fisiología , Músculo Esquelético/fisiología , Propiocepción/fisiología , Adulto , Ejercicio Físico/fisiología , Femenino , Antebrazo/fisiología , Sensación de Gravedad/fisiología , Humanos , Masculino , Persona de Mediana Edad , Husos Musculares/fisiologíaRESUMEN
We retrospectively evaluated 107 fiberoptic bronchoscopies with and without transbronchial lung biopsy (TBLB) in 98 consecutive patients with haematologic malignancies and pulmonary infiltrates. Bronchoalveolar lavage (BAL) was performed in 45 and BAL plus TBLB in 62 procedures. There was no procedure-related severe haemorrhage, pneumothorax or death. Infectious aetiology was identified in 26 of 107 (24%), toxic pneumonitis in 17 of 107 (16%) and neoplastic infiltration in 9 of 107 (8.5%) episodes. Combined BAL and TBLB was significantly superior to BAL alone with respect to the diagnosis of neoplastic infiltrates (p=0.008) and toxic pneumonitis (p<0.001) and should therefore be included in the diagnostic work-up of this patient cohort.
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Biopsia , Neoplasias Hematológicas/patología , Pulmón/patología , Adulto , Anciano , Antineoplásicos/efectos adversos , Biopsia/efectos adversos , Biopsia/métodos , Biopsia/estadística & datos numéricos , Líquido del Lavado Bronquioalveolar , Broncoscopía , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Tecnología de Fibra Óptica , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/diagnóstico , Hemorragia/etiología , Hemorragia/prevención & control , Humanos , Infiltración Leucémica , Enfermedades Pulmonares/diagnóstico , Enfermedades Pulmonares/etiología , Enfermedades Pulmonares/patología , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/complicaciones , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/patología , Transfusión de Plaquetas , Neumonía/inducido químicamente , Neumonía/diagnóstico , Neumonía/etiología , Neumonía/patología , Valor Predictivo de las Pruebas , Estudios RetrospectivosRESUMEN
OBJECTIVE: Gaze direction is known to modulate the activation patterns of sensorimotor areas as seen at the single cell level and in functional magnetic resonance imaging (fMRI). To determine whether such gaze direction effects can be observed in scalp-recorded electroencephalogram (EEG) measures of sensorimotor function we investigated somatosensory evoked potentials (SEPs) and steady state movement related cortical potentials (MRPs). METHODS: In two separate experiments, SEPs were elicited by electrical stimulation of the median nerve (experiment 1) and steady state MRPs were induced by 2 Hz tapping paced by an auditory cue (experiment 2), while subjects directed their gaze 15 degrees to the left or to the right. RESULTS: Gaze direction failed to produce any appreciable differences in the waveforms of the SEPs or MRPs. In particular, there was no effect on peak amplitude, peak latency and peak scalp topography measures of SEP and MRP components, or on spatial or temporal parameters of dipole models of the underlying cortical generators. Additional frequency domain analyses did not reveal reliable gaze-related changes in induced power at electrode sites overlying somatosensory and motor areas, or in coherence between pairs of parietal, central and frontal electrodes, across a broad range of frequencies. CONCLUSIONS: EEG measures of sensorimotor function, obtained in a non-visual motor task, are insensitive to modulatory effects of gaze direction in sensorimotor areas that are observable with fMRI.
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Electroencefalografía , Potenciales Evocados Motores/fisiología , Potenciales Evocados Somatosensoriales/fisiología , Fijación Ocular/fisiología , Movimiento/fisiología , Estimulación Eléctrica , Dedos/fisiología , Humanos , Imagen por Resonancia Magnética , Nervio Mediano/fisiología , Corteza Motora/fisiología , Corteza Somatosensorial/fisiologíaRESUMEN
Most algorithms for blind source separation (BSS) or independent component analysis (ICA) assume an equal number of sources as sensors. For multichannel electrophysiological recordings, such as the electroencephalogram (EEG), however, there are often far fewer sources of neurophysiologically relevant activity than the number of sensors. This adds a model order estimation problem to the source separation problem. Conventional estimates of the number of sources are based on the dominant eigenvalues of the data covariance matrix, obtained from principal component analysis (PCA), whose corresponding eigenvectors are also used for prewhitening. It is well known that PCA is susceptible to noise, leading to incorrect model order estimates and data distortion, which in turn limit the accuracy of the source estimates. It is therefore highly desirable to determine the correct number of sources and their spatial topographies directly, without PCA-based data truncation or prewhitening. In this work, we present a stepwise BSS method for extracting only the sources necessary for a sufficiently good least-square fit to the data. This simultaneously yields model order and source estimates, which we examine at different noise levels. We also show how only a few neurophysiologically meaningful components can be extracted from 25-channel ictal EEG.
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Independent component analysis (ICA) methods are being increasingly applied to the analysis of electromagnetic (EM) brain signals. However, these powerful techniques still generally require subjective a posteriori analysis in order to visualise neurophysiologically meaningful components in the outputs. Standard implementations of ICA are restrictive mainly due to the square mixing assumption (i.e., as many sources as measurement channels) - this is especially so with large multichannel recordings. There are many instances in neurophysiological analysis where there is strong a priori information about the signals being sought; as in tracking the changing scalp topographies of rhythmic activities. Through constraining the ICA solution it is possible to extract signals that are statistically independent, yet which are similar to some reference signal which incorporates the a priori information. We demonstrate this method on a multichannel recording of an epileptiform electroencephalogram (EEG), where we automate the repeated simultaneous extraction of both rhythmic seizure activity, as well as alpha-band activity, over an epoch of EEG. Subjective analysis of the results shows scalp topographies with realistic spatial distributions which conform to our neurophysiologic expectations. This work shows that constraining ICA can be a very useful technique, especially in automated systems and we demonstrate that this can be successfully applied to EM brain signal analysis.