Vascular dysfunction and heart failure: Epiphenomenon or etiologic agent?

Endothelial function plays a key role in the local regulation of vascular tone. Alterations in endothelial function may result in impaired release of endothelium-derived relaxing factors or increased release of endothelium-derived contracting factors. Heart failure may impair endothelial function by means of reduced synthesis and release of nitric oxide (NO) or by increased degradation of NO and increased production of endothelin-1. Endothelial dysfunction may worsen heart function by means of peripheral effects, causing increased afterload and central effects such as myocardial ischemia and inducible nitric oxide synthase (iNOS)-induced detrimental effects. Evidence from clinical studies has suggested that there is a correlation between decreased endothelial function and increasing severity of congestive heart failure (CHF). Treatments that improve heart function may also improve endothelial dysfunction. The relationship between endothelial dysfunction and heart failure may be masked by the stage of endothelial dysfunction, the location of vessels being tested, and the state of endothelial-dependent vasodilatation response.

Is the allegiance effect an epiphenomenon of true efficacy differences between treatments? a meta-analysis

Many meta-analyses of comparative outcome studies found a substantial association of researcher allegiance (RA) and relative treatment effects. Therefore, RA is regarded as a biasing factor in comparative outcome research (RA bias hypothesis). However, the RA bias hypothesis has been criticized as causality might be reversed. That is, RA might be a reflection of true efficacy differences between treatments (true efficacy hypothesis). Consequently, the RA-outcome association would not be indicative of bias but an epiphenomenon of true efficacy differences. This meta-analysis tested the validity of the true efficacy hypothesis. This was done by controlling the RA-outcome association for true efficacy differences by restricting analysis to direct comparisons of treatments with equivalent efficacy. We included direct comparisons of different versions of trauma-focused therapy (TFT) in the treatment of posttraumatic stress disorder (PTSD). RA was measured from the research reports. Relative effect sizes for symptoms of PTSD were calculated. Random effects meta-regression was conducted. Twenty-nine comparisons of TFTs from 20 studies were identified. Initial heterogeneity among relative effect sizes was low. RA was a significant predictor of outcome and explained 12% of the variance in outcomes. The true efficacy hypothesis predicted the RA-outcome association to be zero; however, a substantial association was found. Thus, this study does not support the true efficacy hypothesis. Given findings from psychotherapy research and other fields that support a biasing influence of researcher preferences, RA should be regarded as a causal factor and conceptualized as a threat to the validity of conclusions from comparative outcome studies.

Is the relation between early post-session reports and treatment outcome an epiphenomenon of intake distress and early response? A multi-predictor analysis in outpatient psychotherapy

The early phase of psychotherapy has been regarded as a sensitive period in the unfolding of psychotherapy leading to positive outcomes. However, there is disagreement about the degree to which early (especially relationship-related) session experiences predict outcome over and above initial levels of distress and early response to treatment. The goal of the present study was to simultaneously examine outcome at post treatment as a function of (a) intake symptom and interpersonal distress as well as early change in well-being and symptoms, (b) the patient's early session-experiences, (c) the therapist's early session-experiences/interventions, and (d) their interactions. The data of 430 psychotherapy completers treated by 151 therapists were analyzed using hierarchical linear models. Results indicate that early positive intra- and interpersonal session experiences as reported by patients and therapists after the sessions explained 58% of variance of a composite outcome measure, taking intake distress and early response into account. All predictors (other than problem-activating therapists' interventions) contributed to later treatment outcomes if entered as single predictors. However, the multi-predictor analyses indicated that interpersonal distress at intake as well as the early interpersonal session experiences by patients and therapists remained robust predictors of outcome. The findings underscore that early in therapy therapists (and their supervisors) need to understand and monitor multiple interconnected components simultaneously

Glyt-1 expression in cultured human Muller cells and intact retinae

In this study, we demonstrate that Muller cells cultured from human retinas are capable of strongly expressing the glycine transporter Glyt-1 as assessed by immunocytochemistry. By contrast, intact normal and pathological human retinas exhibit Glyt-1 immunoreactivity only in neurons. These data suggest that Glyt-1 expression in cultured Muller cells is an epiphenomenon associated with culturing in vitro, rather than a normal physiological or even pathophysiological phenomenon in vivo. (C) 2001 Wiley-Liss, Inc.

Insights into the clinical and functional significance of cardiac autonomic dysfunction in Chagas disease

INTRODUCTION: Exclusive or associated lesions in various structures of the autonomic nervous system occur in the chronic forms of Chagas disease. In the indeterminate form, the lesions are absent or mild, whereas in the exclusive or combined heart and digestive disease forms, they are often more pronounced. Depending on their severity these lesions can result mainly in cardiac parasympathetic dysfunction but also in sympathetic dysfunction of variable degrees. Despite the key autonomic effect on cardiovascular functioning, the pathophysiological and clinical significance of the cardiac autonomic dysfunction in Chagas disease remains unknown. METHODS: Review of data on the cardiac autonomic dysfunction in Chagas disease and their potential consequences, and considerations supporting the possible relationship between this disturbance and general or cardiovascular clinical and functional adverse outcomes. RESULTS: We hypothesise that possible consequences that cardiac dysautonomia might variably occasion or predispose in Chagas disease include: transient or sustained arrhythmias, sudden cardiac death, adverse overall and cardiovascular prognosis with enhanced morbidity and mortality, an inability of the cardiovascular system to adjust to functional demands and/or respond to internal or external stimuli by adjusting heart rate and other hemodynamic variables, and immunomodulatory and cognitive disturbances. CONCLUSIONS: Impaired cardiac autonomic modulation in Chagas disease might not be a mere epiphenomenon without significance. Indirect evidences point for a likely important role of this alteration as a primary predisposing or triggering cause or mediator favouring the development of subtle or evident secondary cardiovascular functional disturbances and clinical consequences, and influencing adverse outcomes.

Humoral immunity in brain aging and Alzheimer's disease.

Although the contribution of inflammatory processes in the etiology of late-onset Alzheimer's disease (AD) has been suspected for years, most studies were confined to the analysis of cell-mediated immunological reactions thought to represent an epiphenomenon of AD lesion development. Based on the traditional view of the "immunological privilege" of the brain, which excludes a direct access of human immunoglobulins (Ig) to the central nervous system under normal conditions, little attention has been paid to a possible role of humoral immunity in AD pathogenesis. In the first part of this review, we summarize evidences for a blood-brain barrier (BBB) dysfunction in this disorder and critically comment on earlier observations supporting the presence of anti-brain autoantibodies and immunoglobulins (Ig) in AD brains. Current concepts regarding the Ig turnover in the central nervous system and the mechanisms of glial and neuronal Fc receptors activation are also discussed. In the second part, we present new ex vivo and in vitro data suggesting that human immunoglobulins can interact with tau protein and alter both the dynamics and structural organization of microtubules. Subsequent experiments needed to test this new working hypothesis are addressed at the end of the review.

Oscillations, phase-of-firing coding, and spike timing-dependent plasticity: an efficient learning scheme

Recent experiments have established that information can be encoded in the spike times of neurons relative to the phase of a background oscillation in the local field potential—a phenomenon referred to as “phase-of-firing coding” (PoFC). These firing phase preferences could result from combining an oscillation in the input current with a stimulus-dependent static component that would produce the variations in preferred phase, but it remains unclear whether these phases are an epiphenomenon or really affect neuronal interactions—only then could they have a functional role. Here we show that PoFC has a major impact on downstream learning and decoding with the now well established spike timing-dependent plasticity (STDP). To be precise, we demonstrate with simulations how a single neuron equipped with STDP robustly detects a pattern of input currents automatically encoded in the phases of a subset of its afferents, and repeating at random intervals. Remarkably, learning is possible even when only a small fraction of the afferents (~10%) exhibits PoFC. The ability of STDP to detect repeating patterns had been noted before in continuous activity, but it turns out that oscillations greatly facilitate learning. A benchmark with more conventional rate-based codes demonstrates the superiority of oscillations and PoFC for both STDP-based learning and the speed of decoding: the oscillation partially formats the input spike times, so that they mainly depend on the current input currents, and can be efficiently learned by STDP and then recognized in just one oscillation cycle. This suggests a major functional role for oscillatory brain activity that has been widely reported experimentally.

Autoanticorps en neurologie: implications cliniques [Autoantibodies in neurological diseases: clinical implications]

Autoantibodies are defined as antibodies directed against self antigens, i.e., against a normal antigenic endogenous tissue constituent. They can be the immediate cause of the neurological syndrome or be detected as an epiphenomenon of the pathogenic process. Autoantibodies are often considered useful biomarkers for the improvement of diagnostic accuracy, for the staging of disease progression or for the follow up of a biological response to a therapeutic intervention. The purpose of this article is to review the autoantibodies that are available to investigate immune-mediated neurological conditions. The detection of some of these autoantibodies may help the clinician to establish a definite diagnosis which may further facilitate the therapeutic decision.

Relationship of cytokines and cytokine signaling to immunodeficiency disorders in the mouse

The contributions of cytokines to the development and progression of disease in a mouse model of retrovirus-induced immunodeficiency (MAIDS) are controversial. Some studies have indicated an etiologic role for type 2 cytokines, while others have emphasized the importance of type 1 cytokines. We have used mice deficient in expression of IL-4, IL-10, IL-4 and IL-10, IFN-g, or ICSBP - a transcriptional protein involved in IFN signaling - to examine their contributions to this disorder. Our results demonstrate that expression of type 2 cytokines is an epiphenomenon of infection and that IFN-g is a driving force in disease progression. In addition, exogenously administered IL-12 prevents many manifestations of disease while blocking retrovirus expression. Interruption of the IFN signaling pathways in ICSBP-/- mice blocks induction of MAIDS. Predictably, ICSBP-deficient mice exhibit impaired responses to challenge with several other viruses. This immunodeficiency is associated with impaired production of IFN-g and IL-12. Unexpectedly, however, the ICSBP-/- mice also develop a syndrome with many similarities to chronic myelogenous leukemia in humans. The chronic phase of this disease is followed by a fatal blast crisis characterized by clonal expansions of undifferentiated cells. ICSBP is thus an important determinant of hematopoietic growth and differentiation as well as a prominent signaling molecule for IFNs

Le mythe de la chanson québécoise : une étude sur les liens entre la tradition orale et le mouvement chansonnier des années soixante

Il est à noter que le texte de La Manikoutai a été reproduit dans ce mémoire (voir l’annexe 4, p. xv-xvii), avec l’aimable autorisation de Francyne Furtado des Nouvelles Éditions de l’Arc.

Kant en los problemas de filosofía de la mente contemporánea entre D. Davidson y J. Kim: un argumento a favor del Monismo Anómalo

El Monismo Anómalo que Donald Davidson postuló como posible derrotero a propósito de los problemas latentes en filosofía de la mente contemporánea ha sido víctima de serias críticas, en especial aquellas planteadas por Jaegwon Kim. Sin embargo, una lectura que incluya las referencia que Davidson hizo del proyecto que Kant desarrolló en la Tercera Antinomia de la Razón Pura puede servir para ofrecer una lectura a favor de su proyecto.

Traumatic subdural hygromas: Proposed pathogenesis based classification

Background: Traumatic subdural hygroma (TSHy) is an accumulation of cerebrospinal fluid (CSF) in the subdural space after head injury. It appears to be relatively common, but its onset time and natural history are not well defined. Considered a benign epiphenomenon of trauma, the pathogenesis of TSHy is still unclear and many questions remain unanswered. This study adds to the information on TSHy, and proposes a classification based on pathogenesis.Methods: Thirty-four consecutive adult patients with TSHy were analyzed for clinical evolution and serial CT scan, during a period of several months. TSHy diagnosis was based on published CT scan criteria of hypodense subdural collection after trauma, without enhancement and neomembrane, with a minimum distance of 3 mm between the skull and brain. Ventricle size was analyzed by calculating the bicaudate index (BCI). For comparison, the BCI was measured from CT scan at three moments: admission, at time of TSHy diagnosis, and from last CT scan.Results: There were 34 patients, aged between 16 and 85 years (mean 40), half of them were below 40 years. Road traffic crashes were the main cause of head injury. The mean time for hygroma diagnosis was 9 days. Twenty-one patients (61.8%) underwent conservative treatment for TSHy and 13 (38.2%), surgical treatment. TSHy are early lesions and can be detected in the first 24 hours after trauma, usually as small subdural effusion (SSEff). Based on clinical and CT scan findings, we divided the 34 patients into 3 groups, (Ia and Ib) without evident mass effect and (II) with evident mass effect. Group Ia includes patients without ventricle dilation; Ib, patients with associated ventricle dilations.Conclusions: SSEff detected in the first 24 hours posttrauma in our series evolved into TSHy suggesting that this is an early lesion; all THSy were divided in three groups according to the pathophysiologic mechanism. These three groups probably represent a continuum of CSF absorption impairment. Group la represents what most authors consider a simple hygroma, with no impairment on CSF absorption. Group Ib represent the external hydrocephalus form with various degrees of CSF imbalance, and group II were the cases presenting marked mass effect.

Stimulus-induced gamma activity in the electrocorticogram of freely moving telemetric implanted rats: the neuronal signature of novelty detection

During this thesis a new telemetric recording system has been developed allowing ECoG/EEG recordings in freely behaving rodents (Lapray et al., 2008; Lapray et al., in press). This unit has been shown to not generate any discomfort in the implanted animals and to allow recordings in a wide range of environments. In the second part of this work the developed technique has been used to investigate what cortical activity was related to the process of novelty detection in rats’ barrel cortex. We showed that the detection of a novel object is accompanied in the barrel cortex by a transient burst of activity in the γ frequency range (40-47 Hz) around 200 ms after the whiskers contact with the object (Lapray et al., accepted). This activity was associated to a decrease in the lower range of γ frequencies (30-37 Hz). This network activity may represent the optimal oscillatory pattern for the propagation and storage of new information in memory related structures. The frequency as well as the timing of appearance correspond well with other studies concerning novelty detection related burst of activity in other sensory systems (Barcelo et al., 2006; Haenschel et al., 2000; Ranganath & Rainer, 2003). Here, the burst of activity is well suited to induce plastic and long-lasting modifications in neuronal circuits (Harris et al., 2003). The debate is still open whether synchronised activity in the brain is a part of information processing or an epiphenomenon (Shadlen & Movshon, 1999; Singer, 1999). The present work provides further evidence that neuronal network activity in the γ frequency range plays an important role in the neocortical processing of sensory stimuli and in higher cognitive functions.

Is IgG galactosylation the relevant factor for pregnancy-induced remission of rheumatoid arthritis?

During pregnancy, most patients with rheumatoid arthritis (RA) experience spontaneous improvement of their disease activity. Among the soluble candidates that have been investigated in search for the most relevant disease-remitting factor are the galactosylation levels of immunoglobulin G (IgG). In RA, a higher percentage of IgG lacking the terminal galactose residues, thought to play a pro-inflammatory role, is found. During pregnancy, however, IgG galactosylation levels increase and correlate with improved disease activity. The question remains whether the increase in IgG galactosylation during pregnancy is a mere epiphenomenon or a true remission-inducing factor.

Moving along the mental time line influences the processing of future related words

Abstract concepts like numbers or time are thought to be represented in the more concrete domain of space and the sensorimotor system. For example, thinking of past or future events has a physical manifestation in backward or forward body sway, respectively. In the present study, we investigated the reverse effect: can passive whole-body motion influence the processing of temporal information? Participants were asked to categorize verbal stimuli to the concepts future or past while they were displaced forward and backward (Experiment 1), or upward and downward (Experiment 2). The results showed that future related verbal stimuli were categorized faster during forward as compared to backward motion. This finding supports the view that temporal events are represented along a mental time line and that the sensorimotor system is linked to that representation. We showed that body motion is not just an epiphenomenon of temporal thoughts. Passive whole-body motion can influence higher-order temporal cognition.