[Awareness disorders in Alzheimer's disease and in mild cognitive impairment]. / Conscience des troubles dans la maladie d'Alzheimer et le mild cognitive impairment.

INTRODUCTION: Awareness disorders in Alzheimer's disease still remains unclear despite much research regarding this phenomenon. Papers report various and contrasted results with varying frequency from one study to another. Hence, the interest in awareness in Alzheimer's disease remains limited. Nevertheless, this symptom is closely associated with caregivers' burden and increases the patient's dependency, since the patient is unable to avoid dangers, requiring some care services or institutionalization The purpose of this current review is to recall the main neuro-anatomical and theoretical basis of awareness disorders, and to highlight the recent findings in Alzheimer's disease and in its pre-clinical stages. METHOD: With this in mind, we have conducted a non-exhaustive search using the pubmed online database to collect the most important reviews and the most recent findings regarding awareness disorders in Mild Cognitive Impairment (MCI) and/or in Alzheimer's disease. LITERATURE FINDINGS: In Alzheimer's disease, the links between awareness disorders and other variables, such as severity of dementia or depression, change from one study to the other and do not permit one to understand whether unawareness is an intrinsic or extrinsic reaction to the pathological process itself. Recent results suggest executive, cognitive and behavioral correlates more than psychopathological correlates, although the latter cannot be excluded. In Mild Cognitive Impairment, studies show varied results. Some studies report that patients suffering from Mild Cognitive Impairment can be compared to healthy control subjects and both groups have better awareness than patients with Alzheimer's disease. However, other studies show contrary results and awareness disorders might be a predictor of conversion from Mild Cognitive Impairment to dementia, as with apathy, in which the ability to cope with difficulties represents one of the main features. DISCUSSION: These controversial results are due to the heterogeneity of Alzheimer patients and in particular of MCI patients, but also to various conceptions of awareness disorders in Alzheimer's disease; none of them, however, taking into account all its diversity and complexity. Thus, neurological approaches underline neuropsychological dysfunctions linked to right frontal and/or hemispheric damage but are based on brain injury or strokes, which are events that differ greatly from a neurodegenerative disease involving progressive cognitive, emotional and social disturbances. Psychiatric approaches have taken into account the various aspects of insight, which before were often forbidden and reduced to a categorical point of view, and so could contribute to a better understanding of awareness disorders in Alzheimer's disease. However, these aspects have been conceptualized for psychiatric patients, suffering from positive symptoms, where compliance in treatment is the central key. Insight in neurological diseases is more focused on negative symptoms and generally concerns a basic perception of impairments in mainly cognitive domains. Moreover, modeling has often opposed neurological and psychological mechanisms, so awareness disorders are out of scope of a primary and secondary symptomatology. Although some authors have proposed to take into account these two mechanisms (unawareness and denial), clinical practice has shown that it was impossible to distinguish them both. Finally, some social cognitive approaches are able to demonstrate that there is no correlation between severity of dementia and awareness disorders. Nevertheless, the Self-concept, underlying this point of view, does not permit distinguishing neuropsychological from psycho-social factors. Moreover, only one evaluation tool based on Self-modeling in Alzheimer's disease exists, and to conceptualize Self in a specific pathology does not permit the comparison of this pathology to others or to healthy control subjects. So, the authors present the multidimensional model proposed by Clare et al., and some perspectives to stimulate future research, and perform potential meta-analyses.

[Late onset spondyloarthropathy misdiagnosed as polymyalgia rheumatica]. / Spondyloarthropathies tardives se présentant sous le masque d'une pseudopolyarthrite rhizomélique.

PURPOSE: Polymyalgia rheumatica (PMR) is a frequent cause for long-term corticosteroid therapy. Management of PMR is difficult and recommendations (regarding diagnosis and treatment) from the British Society of Rheumatology have been recently published in order to avoid false diagnosis and unnecessary corticosteroid therapy. On the other hand, late onset spondyloarthropathies are difficult to diagnose due to their various presentation (peripheral and axial manifestations, usually associated with severe systemic manifestations) and the absence of validated diagnosis criteria in the elderly. METHODS: We report on eight patients, who all of them initially responding to Bird's criteria for PMR, and whose outcome was refractory PMR with multiple flares, poor therapeutic response, with inability to taper steroids. RESULTS: After a mean follow-up of 25 months, a diagnosis of late onset spondyloarthropathy was done in all theses patients based on clinical history, physical examination, and spine MRI. In four of the cases the use of TNFα blockers allowed to taper corticosteroid and to control the disease. Retrospectively, the diagnosis at presentation was difficult. CONCLUSION: Among PMR patients with poor response to corticosteroids and multiple flares, the possibility of a late onset spondyloarthropathy should be discussed. There is an unmet need for validated diagnosis criteria in such patients.

Adaptive notification framework for smart nursing home.

This paper presents an adaptive notification framework which allows to optimally deliver and handle multimedia requests and alerts in a nursing home. This framework is operated with various applications (e.g., health alert, medicine reminder, and activity proposition) and has been evaluated with different real end-users (elderly resident and medical staff) in a pilot site. Results of these evaluations are presented and highlight the added value of the framework technology to enhance the quality of life of elderly people as well as the efficiency of the medical staff.

Sterolic and triterpenoidic constituents of stem bark of Drypetes gossweileri.

Four compounds have been identified from the stem bark of Drypetes gossweileri by means of 1H- and 13C-NMR spectroscopy, stearic acid, methyl putranjate, and two new compounds: stigmasterol stearate and beta-sitosterol stearate.

Mechanisms of inhibition of Cryptococcus neoformans by human lymphocytes.

Recently, our laboratory and others have demonstrated that human peripheral blood T and NK lymphocytes directly inhibit the growth of Cryptococcus neoformans. In this study, we further define the conditions under which lymphocyte-mediated fungistasis against C. neoformans occurs and examine whether mechanisms implicated in lymphocyte-mediated activities against other target cells are also involved in anticryptococcal activity. The addition of whole or broken heat-killed C. neoformans modestly inhibited lymphocyte-mediated fungistasis, whereas other particulates had no effect. The hydroxyl radical scavenger catechin, but not diethyl urea or propyl gallate, profoundly inhibited fungistasis. Salicylic acid inhibited fungistasis in a dose-dependent fashion. However, two other cyclooxygenase inhibitors, piroxicam and indomethacin, had no effect, suggesting that the mechanism of inhibition by salicylic acid was cyclooxygenase independent. Reagent prostaglandin E2, at concentrations shown by others to inhibit NK cell-mediated bactericidal and tumorlytic activities, had no effect on lymphocyte-mediated fungistasis. The addition of selected monoclonal antibodies or ligands reactive with receptors on human lymphocytes had no significant effect on lymphocyte-mediated fungistasis. Acapsular, small-capsuled, and large-capsuled C. neoformans organisms were inhibited by lymphocytes to an approximately equal extent. These data demonstrate that lymphocyte-mediated activity against C. neoformans proceeds regardless of the presence of capsule and by mechanisms at least in part dissimilar from those seen with other target cells.

Direct activity of human T lymphocytes and natural killer cells against Cryptococcus neoformans.

Lymphocytes constitute a critical component of host defenses against cryptococcosis. Previously, we demonstrated that human lymphocytes cultured with interleukin-2 formed conjugates with, and directly inhibited the growth of, Cryptococcus neoformans. Here, we explore the anticryptococcal activity of freshly isolated, highly purified populations of human peripheral blood lymphocytes. Lymphocytes were incubated with encapsulated C. neoformans for 24 h, after which the lymphocytes were lysed, dilutions and spread plates were made, and CFU were counted. Fungistasis was determined by comparing growth in wells with and without lymphocytes. Nylon wool-nonadherent peripheral blood mononuclear cells (NWNA PBMC) were highly fungistatic, even if either T cells or natural killer (NK) cells were depleted by panning. A mixed population of T cells and NK cells, obtained by rosetting NWNA PBMC with sheep erythrocytes, completely inhibited cryptococcal growth, whereas the nonrosetting cells had little fungistatic activity. CD4+, CD8+, and CD16/56+ lymphocytes, isolated by positive immunoselection, had potent growth-inhibitory activity. In contrast, purified B cells had no activity. Fungistasis was seen even in the absence of opsonins. Antifungal activity was markedly diminished when surface receptors on NWNA PBMC were cleaved by treatment with trypsin or bromelain. Supernatants from stimulated lymphocytes or concentrated lymphocyte sonicates were not active. Lymphocyte-mediated fungistasis was seen with two different strains of C. neoformans. CD4+, CD8+, and CD16/56+ lymphocytes formed conjugates with C. neoformans, as observed under Nomarski differential interference contrast microscopy and videomicroscopy. These data demonstrate that freshly isolated peripheral blood T cells and NK cells have the capacity to bind and directly inhibit the growth of C. neoformans.

Phenotypic and functional characterization of human lymphocytes activated by interleukin-2 to directly inhibit growth of Cryptococcus neoformans in vitro.

Recently we demonstrated that the nonadherent (to plastic) fraction of human PBMC could be activated by IL-2 to inhibit Cryptococcus neoformans growth. Here we characterize the antifungal effector cells. Depletion by panning of natural killer (NK) (CD16+, CD56+) cells from nylon wool-treated, IL-2-activated PBMC markedly decreased lytic activity against a tumor cell target (K562) but did not affect antifungal activity. Panning out T (CD3+, CD5+) cells enhanced activity against tumor cells but partially abrogated activity against C. neoformans. IL-2-activated T cells of 95% purity, obtained by panning out NK cells from PBMC forming rosettes with sheep erythrocytes, had excellent antifungal activity but suboptimal antitumor activity. The nonrosetted cells (which were virtually free of T cells and enriched for NK cells) had both antitumor and antifungal activity, even if cultured without IL-2. CD4+, CD8+, and CD56+ cells, purified by positive selection by panning, directly inhibited cryptococcal growth. Conjugate formation between fungi and both CD56+ and CD5+ effector cells was demonstrated by videomicroscopy and immunoperoxidase staining. Thus, IL-2-activated T cells and NK cells form conjugates with and directly inhibit the growth of C. neoformans. To our knowledge, these data are the first demonstration of human T cells directly inhibiting growth of a microbial target.

Phenomenological perceptions of parental evaluations in depressed and nondepressed college students.

Examined three hypothesis shared in common by several contemporary theoreticians of depression: (1) depressogenic parents maintain unrealistically high ideals for their offspring; (2) depressogenic parents negatively evaluate these offspring; (3) depressive offspring show lowered self-evaluations. Phenomenological perceptions of parental ideals and attitudes were reported by depressed and nondepressed college students (N = 48). These data supported the latter two hypotheses, but not the first. Results are discussed in terms of interpersonal attraction theory as well as in terms of a possible model of mutual influencability in the family interactions of depressives.