Therapeutic patient education in Alzheimer's disease and related disorders: Clinical experience and perspectives.

Therapeutic patient education (TPE) is the process by which health professionals impart information to help patients self-manage their chronic disease: it is an essential part of treatment of long-term diseases and conditions. Memory loss and other cognitive disorders are usually considered as obstacles to TPE for patients with Alzheimer's disease or related disorders (ADRD). Over 100 patients with different forms of ADRD and caregivers have benefited from TPE programs since 2011 at the Limoges University Clinical and Research Memory Center. Participants report better understanding of the disease and improved relationships. TPE may prevent anxiety and depression in patient and in caregivers, and reduce burden of caregivers. General guidelines and perspectives for TPE in ADRD are outlined.

[Interpersonal therapy (IPT) in child psychiatry and adolescent]. / Thérapie interpersonnelle (TIP) en psychiatrie de l'enfant et de l'adolescent.

INTRODUCTION: Depression disorder may become the first cause of morbidity by 2030, according to the World Health Organization. It is actually one of the main causes of disease and handicap in children aged from 10 to 19. The major risk is suicide, whose prevalence is estimated, in France, around 6.7 for 100,000, which is probably underestimated. At present, the discussions about prescription of antidepressants in an adolescent's depression remain intense which is why psychotherapy becomes the first choice of treatment. We propose here to present one of them, Interpersonal PsychoTherapy (IPT), which remains largely unknown in France, and its adaptations in the adolescent population. PRESENTATION OF IPT: IPT is a brief psychotherapy, structured in twelve to sixteen sessions, which was created by Klerman and Weissman in the seventies inspired by the biopsychosocial model of Meyer, interpersonal theory of Sullivan, and attachment theory of Bowlby. It is divided into three parts: the initial phase, the intermediate phase, and the termination phase. ADAPTATION FOR ADOLESCENTS: IPT was adapted for adolescents by Mufson in 1993, but a few modifications must be considered. Parental implication is the first. Indeed, parents, rather than the adolescent, often ask for the consultation; but it is the latter who benefits from the therapy. Parents may be met at some point in the therapy, for example between each phase and at the end. The initial phase is very close for the adolescent as for the adult; but the therapist must be careful about employing the "sick role" which can be used by the adolescent to avoid school, and as a consequence, to exacerbate the interpersonal deficit. The intermediate phase focuses on one of the four interpersonal issues: complicated bereavement, role transition, interpersonal role disputes, and interpersonal deficit. Complicated bereavement may become problematic when prolonged or when the adolescent had complicated relations with the deceased. The therapist essentially works on emotion verbalization. The role of transition is very common during adolescence: children become adults, they pass from high school to college, or their parents get divorced, etc. The patient and the therapist work on giving up the old role with its emotional expression (guilt, anger, and loss), and acquiring new skills, and identifying positive aspects of the new role. Interpersonal role disputes are common during adolescence, with parents or teachers for example. To determine a treatment plan, the therapist may first determine the stage of the role dispute, among impasse, renegotiation, or dissolution, and then work on the communication mode of the patient. At the least, the interpersonal deficit may be the most difficult area to work on because of the risk of psychiatric comorbidity. The therapist must be especially careful about anxious disorder which may complicate the psychotherapy and for which IPT is not the best therapy. The termination phase focuses on the new skills and abilities and works on the future without therapy. IPT is one of the psychotherapies recommended in the treatment of depression disorder in the international recommendations. But in France, all psychotherapies are considered equally. This may be a consensual approach, but the authors wonder if it is the best, especially to motivate research in the psychotherapy field. OTHER INDICATIONS: Finally, IPT has been developed in other indications in the past years, and many others are presently in research projects: depression during pregnancy, prevention of depression relapse, eating disorders, attention deficit and hyperactivity disorder, self-harm for example. CONCLUSION: Its validity, simplicity and efficacy should stimulate psychiatrists and residents to train themselves to IPT.

[Diogenes syndrome and Hoarding disorder: Same or different?] / Syndrome de Diogène et Hoarding disorder : une même entité ?

INTRODUCTION: In 2013, the American Psychiatric Association published the DSM-5. In this new version, new diagnoses were proposed including the Hoarding disorder. In the French semeiology, the Diogenes syndrome is described, among other symptoms, by a pathological tendency to accumulate objects called syllogomania which is very close to hoarding. This paper explores the similarities and differences between the two syndromes. DESCRIPTION: The Diogenes syndrome was first described in 1966 but was officially named for the ancient Greek philosopher in 1975 by Clark. Its frequency is around five for 100,000 persons. Many aetiologies have been known to be associated with the Diogenes syndrome: schizophrenia, dementia - especially frontotemporal type, anxiety disorders, mood disorders, and substance abuse - especially alcohol abuse. The diagnostic requires one major criterion, the inability to ask for medical or social help, and one of three minor criteria: a pathological relationship to the body, which leads to somatic illness; a pathological relationship to the society, which leads to a progressive exclusion from it; and finally, a pathological link with objects. This last criterion is very interesting because it is closely related to the Hoarding syndrome: indeed, patients with syllogamania, as also named, have a tendency to hoard every object they find. At the end, their homes are full of useless objects, and some living places can be unusable because they are cluttered and congested. This last point is similar to the definition given in the DSM-5 for the Hoarding disorder which describes a persistent difficulty parting with possessions; distress associated with discarding possessions; and accumulations that congest and clutter active living areas. The Hoarding disorder was first part of the Obsessive and compulsive disorders, but it has progressively appeared that it could be individualized with its own prevalence of 2.3% to 14% lifetime. Genetical studies have shown that at least 50% of patients suffering from excessive hoarding had a relative with a dimension of hoarding. Finally, Mattaix-Cols et al. decided to create a new syndrome in the DSM-5, and the Hoarding disorder was born. DISCUSSION: The discussion begins with relationships between the Hoarding disorder and the Diogenes syndrome. A patient with hoarding, and a poor insight, could be very isolated, and could persist in a lack of calling for help, because of not being aware of his pathology. Thus, it could be diagnosed as a Hoarding syndrome with a poor insight, or as a Diogenes syndrome, with the first major criterion (lack of calling for help) and one of the three minor criteria, the syllogomania, or hoarding. Moreover, some authors have described old people living for many years with a tendency to hoard. Progressively, some of them had a congested and cluttered home, and a few were living in squalor, a description very close to the Diogenes syndrome. Finally, we discuss the comorbidity of Hoarding disorder and Diogenes syndrome. In particular, the first one is associated with Attention deficit and hyperactivity disorders; and some authors also described the links between ADHD, bipolar disorder and frontotemporal dementia which is one of the aetiologies of the Diogenes syndrome. A psychodynamic model in which ADHD, Hoarding disorder and Diogenes syndrome are linked can be imagined, and the last one could be an overlooked evolution of the two first syndromes. CONCLUSION: In conclusion, we can imagine a dimensional model, based on two dimensions: hoarding and squalor. Hoarding disorder is the major expression of the first dimension, and Diogenes syndrome the major expression of the second. Both of them could be a different expression of one central aetiology. More studies are needed to complete this vision.

Epidemiology of peripheral artery disease in elder general population of two cities of Central Africa: Bangui and Brazzaville.

OBJECTIVES: Peripheral artery disease (PAD) is a common condition in Western countries, mostly in the elderly. Little is known about the epidemiology of PAD in Africa. We sought to determine the prevalence of this condition in the elderly in two community-dwelling cohorts in Central Africa. DESIGN: Prospective cross-sectional survey in general population over the age of 65 years in Bangui (Central African Republic) and Brazzaville (Congo). METHODS: We conducted a systematic door-to-door survey in two representative districts of each city. Demographic, clinical and biological data were collected. The ankle-brachial index (ABI) was used to detect PAD (ABI ≤ 0.90). RESULTS: Among the 976 participants, the prevalence of PAD was 15.0% in Bangui and 32.4% in Brazzaville, increasing with age. Adjusted to age, regular alcohol consumption was protective for women in Bangui (OR = 0.50, CI95%:0.25-0.98) and men in Brazzaville (OR = 0.43, CI95%:0.21-0.88). Hypertension was associated with PAD in women (OR = 4.14, CI95%:1.65-10.42 in Bangui and OR = 2.17, CI95%:1.16-4.06 in Brazzaville). Diabetes and smoking showed different associations according to gender and city. CONCLUSIONS: This first population study in Central Africa highlights the high prevalence of PAD in the older population, and emphasizes specificities regarding the risk factors, being different from data published in Western countries.

[Epidemiology of dementia in elderly living in the 3rd borough of Bangui (Central African Republic)]. / Épidémiologie des démences chez les personnes âgées dans le troisième arrondissement de la ville de Bangui (République Centrafricaine).

Given the gradual improvement of living conditions and aging, dementia and related syndromes are becoming serious problems in the developing countries. A cross-sectional door to door type study in neighbourhood, was conducted from October 2008 to January 2009, in the general population in Bangui, order to help get a better understanding of the prevalence and risk factors of dementia among people over 65 living in the Central African capital. Of the 496 elderly respondents, 188 had cognitive disorders. After a neuropsychological examination, 40 of these subjects were diagnosed with dementia. The prevalence of dementia was 8.1% (IC 95% = [5.7-10.5]). The average age of subjects with dementia, ranging from 65 to 90 years, was 76.0 ± 7.1 years. There was a significant risk of developing dementia for an increase of ten years old (OR = 2.6, 95% CI [1.5 to 4.5]). The sex-ratio was 6/34. 82.5% of the demented had never attended school. 70.0% showed a state of malnutrition (BMI ≤ 18,5 kg/m(2)), significantly associated with dementia (OR = 3.3; IC 95% = [1.5-7.3]). The blood pressure was high in 67.5% of demented which is significantly associated with dementia (OR = 2.4; IC 95% = [1.1-5.4]). A recent change in financial status was a factor significantly associated with dementia (OR = 6.4; IC 95% = [1.8-22.5]). These results support the existence of dementia in urban Africa. The observed prevalence is close to those found in high-income countries. Further studies should be conducted which includes both the rural and urban Africa, to better understand the problem and solutions consider to comprehensive care and prevention axes adapted to our context.

[PerCaDim study: relationship between categorical and dimensional approaches of personality]. / Étude PerCaDim : relations entre approches dimensionnelle et catégorielle de la personnalité

PURPOSE: Personality and its disorders have been the subject of many studies in philosophy, psychology or medicine. Current nosology gives preference to categorical classifications, but a dimensional approach may also be considered. Supported by Cloninger's psychobiological model, it refers to concepts of temperament (novelty seeking, reward dependence, harm avoidance and persistence) and character dimensions (self-directedness, cooperativeness and self-transcendence). Categorical and dimensional approaches do not appear antinomic, and the PerCaDim study tries to verify the hypothesis of correlations existing between them. SUBJECTS AND METHODS: One hundred and eleven patients completed two personality inventories. The dimensional approach was assessed using the TCI-125 (short version of the Temperament and Character Inventory) (Cloninger et al., 1993 [9]), which includes four dimensions of temperament and three dimensions of character. The categorical approach was assessed using Vragenlijst Kenmerken voor van de Persoonlijkheid (VKP) (Duijsens et al., 1993 [15,16]), which defines personality disorders according to DSM III-R (APA, 1987 [1]). RESULTS: The PerCaDim study reveals significant relationships between the dimensions of temperament and character and personality disorders. For dimensions of temperament: novelty seeking is correlated negatively with schizoid personality and positively with antisocial, borderline, histrionic, narcissistic and sadistic personalities. Ten out of 13 personalities from DSM III-R are positively correlated with harm avoidance. Cluster A and obsessive-compulsive personality disorders have negative correlations with reward dependence, whereas five pathological personalities have positive correlations with persistence. For dimensions of character: all personality disorders are negatively correlated with self-directedness. Cooperativeness is negatively correlated with six personality disorders. Among the dimensions of character, only self-transcendence has positive correlations with personality disorders. DISCUSSION: The PerCaDim study highlights various relationships between dimensional and categorical approaches of personality. It shows negative correlations between reward dependence and cluster A personality disorders, positive correlations between novelty seeking and cluster B personality disorders and between harm avoidance and cluster C personality disorders. Self-directedness and cooperativeness character's dimensions seem to reflect the subject's adaptation, because negative correlations were found with all personality disorders. It may be surprising that correlations appear positive between self-transcendence dimension and 12 personality disorders. This result is not striking for "psychotic" personalities, but may be questionable for other personalities. CONCLUSION: These results confirm previous findings that Cloninger's dimensions can objectify personality disorders. Few dimensions of the Temperament and Character Inventory can be considered as vulnerability factors. The use of the Temperament and Character Inventory will most certainly be of good help in the future to detect or prevent a personality disorder in some subjects at risk.

[Sleep disturbances in home caregivers of persons with dementia]. / Troubles du sommeil chez les aidants à domicile de patients atteints de démence.

BACKGROUND: Estimates suggest that there are more than 700,000 adult caregivers of persons with dementia in this country, a large number of whom experience some form of sleep disturbance during the course of their caregiving career. Health care professionals are in the best position to detect and address this significant public health problem. OBJECTIVES: Prospective study of sleep with the main caregivers providing home-care for demented patients. METHODS: This study was performed on elderly persons living at home. Two populations were concerned. The control group concerned 86 old persons living in the area of Limoges (France) and was contacted to join by the senior clubs of this city. The other group concerned caregivers to persons with dementia, living with them at home, and the assessments were done during the patient assessment. Each group had a cognitive evaluation by a Folstein's test and answered a questionnaire to describe their possible sleep difficulties. RESULTS: Sixty-eight caregivers face sleep disturbance versus 25 non-caregiver controls. Caregiver sleep-problems are often linked to sleep disturbances in the care-recipient. Night-time awakenings by persons with dementia are a common precipitating cause of sleep/wake disturbances in vulnerable caregivers. Caregivers awake 2.3 times during the night versus 1.2 for control persons. Caregivers awake earlier (around 6:20) than non-caregivers (around 7:05) and their sleep time is shorter by one hour. Caregivers are more often depressed (28 in 98 versus 13 in 86) and have more often high blood pressure (56 in 98 versus 24 in 86). They received more medications and used more often self-medication. DISCUSSION: Three major contributors to caregiver sleep-disturbance are pointed in this paper: the apparition of caregiver disrupted sleep routines, caregiver burden and depression and the caregiver's physical health status. Successful treatment of a caregiver's sleep disturbance requires careful consideration of each of these contributors. Non-pharmacological options are generally recommended as a first line of treatment for managing sleep disturbances in older adults, including caregivers of persons with dementia.

Metabotropic glutamate receptor 1 activity generates persistent, N-methyl-D-aspartate receptor-dependent depression of hippocampal pyramidal cell excitability.

Metabotropic glutamate receptors (mGluRs) are involved in many forms of neuronal plasticity. In the hippocampus, they have well-defined roles in long-lasting forms of both synaptic and intrinsic plasticity. Here, we describe a novel form of long-lasting intrinsic plasticity that we call (S)-3,5-dihydroxyphenylglycine (DHPG)-mediated long-term depression of excitability (DHPG-LDE), and which is generated following transient pharmacological activation of group I mGluRs. In extracellular recordings from hippocampal slices, DHPG-LDE was expressed as a long-lasting depression of antidromic compound action potentials (cAPs) in CA1 or CA3 cells following a 4-min exposure to the group I mGluR agonist (S)-DHPG. A similar phenomenon was also seen for orthodromic fibre volleys evoked in CA3 axons. In single-cell recordings from CA1 pyramids, DHPG-LDE was manifest as persistent failures in antidromic action potential generation. DHPG-LDE was blocked by (S)-(+)-a-amino-4-carboxy-2-methylbenzeneacetic acid (LY367385), an antagonist of mGluR1, but not 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP), an mGluR5 inhibitor. Although insensitive to antagonists of alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate/kainate and gamma-aminobutyric acid(A) receptors, DHPG-LDE was blocked by antagonists of N-methyl-D-aspartate (NMDA) receptors. Similarly, in single-cell recordings, DHPG-mediated antidromic spike failures were eliminated by NMDA receptor antagonism. Long after (S)-DHPG washout, DHPG-LDE was reversed by mGluR1 antagonism. A 4-min application of (S)-DHPG also produced an NMDA receptor-dependent persistent depolarization of CA1 pyramidal cells. This depolarization was not solely responsible for DHPG-LDE, because a similar level of depolarization elicited by raising extracellular K(+) increased the amplitude of the cAP. DHPG-LDE did not involve HCN channels or protein synthesis, but was eliminated by blockers of protein kinase C or tyrosine phosphatases.

Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor.

A member of the inwardly rectifying potassium channel family was cloned here. The channel, called BIR (Kir6.2), was expressed in large amounts in rat pancreatic islets and glucose-responsive insulin-secreting cell lines. Coexpression with the sulfonylurea receptor SUR reconstituted an inwardly rectifying potassium conductance of 76 picosiemens that was sensitive to adenosine triphosphate (ATP) (IKATP) and was inhibited by sulfonylureas and activated by diazoxide. The data indicate that these pancreatic beta cell potassium channels are a complex composed of at least two subunits--BIR, a member of the inward rectifier potassium channel family, and SUR, a member of the ATP-binding cassette superfamily. Gene mapping data show that these two potassium channel subunit genes are clustered on human chromosome 11 at position 11p15.1.

Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of insulin secretion.

Sulfonylureas are a class of drugs widely used to promote insulin secretion in the treatment of non-insulin-dependent diabetes mellitus. These drugs interact with the sulfonylurea receptor of pancreatic beta cells and inhibit the conductance of adenosine triphosphate (ATP)-dependent potassium (KATP) channels. Cloning of complementary DNAs for the high-affinity sulfonylurea receptor indicates that it is a member of the ATP-binding cassette or traffic ATPase superfamily with multiple membrane-spanning domains and two nucleotide binding folds. The results suggest that the sulfonylurea receptor may sense changes in ATP and ADP concentration, affect KATP channel activity, and thereby modulate insulin release.

Adenosine diphosphate as an intracellular regulator of insulin secretion.

Adenosine triphosphate (ATP)-sensitive potassium (KATP) channels couple the cellular metabolic state to electrical activity and are a critical link between blood glucose concentration and pancreatic insulin secretion. A mutation in the second nucleotide-binding fold (NBF2) of the sulfonylurea receptor (SUR) of an individual diagnosed with persistent hyperinsulinemic hypoglycemia of infancy generated KATP channels that could be opened by diazoxide but not in response to metabolic inhibition. The hamster SUR, containing the analogous mutation, had normal ATP sensitivity, but unlike wild-type channels, inhibition by ATP was not antagonized by adenosine diphosphate (ADP). Additional mutations in NBF2 resulted in the same phenotype, whereas an equivalent mutation in NBF1 showed normal sensitivity to MgADP. Thus, by binding to SUR NBF2 and antagonizing ATP inhibition of KATP++ channels, intracellular MgADP may regulate insulin secretion.

Proposed diagnostic criteria for apathy in Alzheimer's disease and other neuropsychiatric disorders.

There is wide acknowledgement that apathy is an important behavioural syndrome in Alzheimer's disease and in various neuropsychiatric disorders. In light of recent research and the renewed interest in the correlates and impacts of apathy, and in its treatments, it is important to develop criteria for apathy that will be widely accepted, have clear operational steps, and that will be easily applied in practice and research settings. Meeting these needs is the focus of the task force work reported here. The task force includes members of the Association Française de Psychiatrie Biologique, the European Psychiatric Association, the European Alzheimer's Disease Consortium and experts from Europe, Australia and North America. An advanced draft was discussed at the consensus meeting (during the EPA conference in April 7th 2008) and a final agreement reached concerning operational definitions and hierarchy of the criteria. Apathy is defined as a disorder of motivation that persists over time and should meet the following requirements. Firstly, the core feature of apathy, diminished motivation, must be present for at least four weeks; secondly two of the three dimensions of apathy (reduced goal-directed behaviour, goal-directed cognitive activity, and emotions) must also be present; thirdly there should be identifiable functional impairments attributable to the apathy. Finally, exclusion criteria are specified to exclude symptoms and states that mimic apathy.

[Depression and frontal dysfunction: risks for the elderly?]. / Dépression et syndrome frontal: quels risques pour la personne âgée?

BACKGROUND: Frontal lobe syndromes include reduced activity, particularly a diminution of spontaneous activity, lack of drive, inability to plan ahead, and induce a lack of concern. These last points constitute the executive dysfunction syndrome. That executive dysfunction could be the core defect in patients with geriatric or vascular depression, and might be related to frontal-subcortical circuit dysfunction. Sometimes frontal lobe syndromes are associated with restless, aimless, uncoordinated behavior or even disinhibition, increasing the risks of falls and of malnutrition. Some authors have distinguished between lesions of the lateral frontal cortex, most closely linked to the motor structures of the brain, which lead to disturbances of movement and action with perseveration and inertia, and lesions of the orbital and medial areas, interlinked with limbic and reticular systems, damage to which leads to disinhibition and changes of affect. The medial frontal syndrome is marked by akinesia, associated with gait disturbances, and loss of autonomy. For these reasons, it has been proposed that a subtype of depression, "depression-executive dysfunction syndrome" could occur in late life. This assertion was based on clinical, neuropathological, and neuroimaging findings suggesting that frontostriatal dysfunctions contribute to the development of both depression and executive dysfunction and influence the course of depression. Depressive symptomatology, and especially psychomotor retardation and loss of interest in activities, contributed to disability in depression-executive dysfunction syndrome patients. This study is not restricted to major depression. It examined the relationship of executive impairment to the course of depressive symptoms among a psychogeriatric population with dementia or depression in order to assess the consequences of these pathologies on disabilities of aged persons. METHODS: The study was carried out in Limoges (France) during 2006 and 2007. Three hundred and twenty one psychogeriatric outpatients were included after their written agreement. They were assessed using different scales for autonomy, cognition, depression, frontal impairment and these results were compared with the risk of fall, a possible loss of autonomy and a proteino-energical malnutrition. The statistical study was made using the Systat 11 software. The following tests were used: Student Test, Chi(2) test, and the Manova test, which was adjusted to the duration of the disease, the caregiver's age, his/her education level, and level of cognitive impairment. The regression method used was the multiple linear regression method as well as a descending step-by-step analysis. RESULTS: One hundred and thirty six males (77.3+/-7.09 years old) and 185 females (80.4+/-6.5 years old) were recruited. Patients mainly presented with Alzheimer's disease (n=123) and 65 presented an associated depression, 25 presented vascular dementia, 30 a Lewy bodies dementia, 27 a fronto-temporal dementia. Twenty-seven presented psychosis and 40 a Mild Cognitive Impairment. A control group was composed of 33 persons presumed without psychogeriatric pathologies. Depression associated with an executive dysfunction syndrome increased loss of autonomy, the risk of fall and of malnutrition, especially in the case of cognitive impairment. The multivariate regression analysis step-by-step shows an increasing risk of fall in the presence of a depression-executive dysfunction syndrome. Motivation is altered when the patient is depressed. In demented patients, depression significantly increases behavioral disorders, social and familial relationships, and instrumental acts of daily life. It precipitates the risks of falls and of malnutrition. DISCUSSION: The principal finding of this study is that geriatric depression is characterized by impaired executive functioning. In the present study, depressed patients also had a greater tendency to fall and to suffer from malnutrition. Executive processes are fundamental to the daily functioning of depressed older adults, and dysfunction may lead to a lack of compensatory strategies that would improve the outcomes of late-life depression or of increasing dependency as well. In demented patients, depression triggers loss of motivation and executive dysfunction as well. CONCLUSIONS: Depression and executive dysfunction triggers the loss of autonomy, the risk of fall and of malnutrition in elderly patients. The clinical significance of this study is that the delineation of specific executive in depressed elderly patients may facilitate the development of effective treatment interventions, including treatment for geriatric depression.

Association and stoichiometry of K(ATP) channel subunits.

ATP-sensitive potassium channels (K(ATP) channels) are heteromultimers of sulfonylurea receptors (SUR) and inwardly rectifying potassium channel subunits (K(IR)6.x) with a (SUR-K(IR)6.x)4 stoichiometry. Association is specific for K(IR)6.x and affects receptor glycosylation and cophotolabeling of K(IR)6.x by 125I-azidoglibenclamide. Association produces digitonin stable complexes with an estimated mass of 950 kDa. These complexes can be purified by lectin chromatography or by using Ni2(+)-agarose and a his-tagged SUR1. Expression of SUR1 approximately (K(IR)6.2)i fusion constructs shows that a 1:1 SUR1:K(IR)6.2 stoichiometry is both necessary and sufficient for assembly of active K(ATP) channels. Coexpression of a mixture of strongly and weakly rectifying triple fusion proteins, rescued by SUR1, produced the three channel types expected of a tetrameric pore.

A family of sulfonylurea receptors determines the pharmacological properties of ATP-sensitive K+ channels.

We have cloned an isoform of the sulfonylurea receptor (SUR), designated SUR2. Coexpression of SUR2 and the inward rectifier K+ channel subunit Kir6.2 in COS1 cells reconstitutes the properties of K(ATP) channels described in cardiac and skeletal muscle. The SUR2/Kir6.2 channel is less sensitive than the SUR/Kir6.2 channel (the pancreatic beta cell KATP channel) to both ATP and the sulfonylurea glibenclamide and is activated by the cardiac K(ATP) channel openers, cromakalim and pinacidil, but not by diazoxide. In addition, SUR2 binds glibenclamide with lower affinity. The present study shows that the ATP sensitivity and pharmacological properties of K(ATP) channels are determined by a family of structurally related but functionally distinct sulfonylurea receptors.

[Facilitating environment for dementia patients--the Pixel study]. / Environnement contenant chez la personne âgée démente--Etude Pixel.

UNLABELLED: Caregivers of demented outpatients can suffer from poor health, are often anguished and unable to cope with the cared patient, and this burden can generate frailty. OBJECTIVES: This survey attempted to determine the psychological parameters and effective capability influence of the caregiver's Quality of Life (QoL) and vulnerability, and measured the consequences of their alteration. METHODS: 4 categories of situations were studied, according to the angst and coping capability of caregivers. Caregiver's QoL and vulnerability were assessed in these situations. Data were related to the socio-demographic data of both patients and their principal caregivers, and to the patients' medical and therapeutic data. RESULTS: 1,410 and 10 patients diagnosed with dementia who lived at home with their principal caregivers were recruited for this survey. Angst and inability to cope with patients alter caregivers' QoL and was correlated to their vulnerability. Female caregivers were often in these situations, had a poorer QoL and were more vulnerable than men. Caregivers anguished and/or nab to cope with the cared patient were less satisfied with their own care and did not enjoy their relationships with their patients. Caregivers with psychological difficulties and failure to cope had to deal with nutritional difficulties with the demented patient. DISCUSSION: Caregivers' QoL and vulnerability, are related to angst and inability to cope with patients. We could imagine that both patients and caregivers would benefit by taking care of carers.

[Links between life events, traumatism and dementia; an open study including 565 patients with dementia]. / Relation entre événements de vie, traumatismes et démence; étude ouverte portant sur 565 patients déments.

SUMMARY: Ageing is due to a progressive loss of the person's adaptation capability, whereas during this period environmental aggression increases. In the elderly, life events re-present a psychological traumatism that overwhelms the old person and related family, disrupting and fragilising homeostatic balance. A number of authors have suggested a possible link between life traumatisms and the dementia processes. The aim of this study is to reveal the presence of life traumatisms preceding the apparition of the dementia syndrome. METHOD: This is a retrospective and comparative work based on the PIXEL study on complaints and demands from the principle informal caregivers of Alzheimer patients. It includes 565 patients presenting the criterion of dementia as defined by the DSM IV, and questionnaires filled out by the principle caregivers. One item of the questionnaire referred to life events which could have played a part in the development of the disorder. In a second stage, the reported events were classified into 4 distinct categories: loss, repeated or prolonged stress, psychotraumatism and depression-inducing events. The statistics were produced using SAS and Stat 10 software. Student's test, ANOVA and chi2-test were used. RESULTS: 372 caregivers answered the first item (65%); 76 of them believed there was no event while 296 related the disorder to one or several life events (79% of responders, 52% of the sample). These results confirm Persson and Clement's study which evidenced a higher frequency of stressing life events for subjects afflicted with dementia as compared with older people without any psychic disorder. Reported events and their respective frequency: spouse death (15.39%), parents' death (15%), familial difficulty (10.08%), anaesthesia (8.49%), child's death (4.42%), somatic disturbance (4%), depression (3.89%), retirement (3.89%), financial problems (2.65%), loneliness (2.65%), removal (1.76%), fall (1%), alcohol (0.8%), traumatism (0.53%), spouse care (0.35%), leaving for home care, storm and caregiver change in life (0.17%). Regrouping the data: 82.71% of the answers can be connected to prolonged stress, 62.85% to real or symbolic loss, 39% to a psychotraumatic event and finally, most of these events can potentially induce depression. DISCUSSION: Some of the events refer to difficulties concerning people close to the subject (death of a close relation, hospitalisation of husband or wife) in a period when the loss of autonomy or handicap means greater dependence on surrounding people. General anaesthesia is mentioned by 48 caregivers. In fact, this usually implies surgery, the presence of organic pathology or the need for hospitalisation, which we know has a destabilizing effect in the elderly. It is therefore not surprising that 23 answers mentioned somatic disorders (4% of the sample). According to Leger, it's mostly a loss type event which is implied in the elderly. Such losses would induce a weakening of cognitive stimulation which could decompensate an infraclinical dementia or accelerate an emerging dementia process. Antecedents of depressive illness are considered as an element of risk for the development of Alzheimer's disease. Depression is spontaneously mentioned by 22 caregivers. We must add the many reported life events which are well known to induce depression in older people. Most of the events considered in this study are liable to provoke manic mood swings. Depression resulting from life events can be considered either as an affection occurring along with dementia or as the aggravating factor of an infraclinical process or, finally, as an additional factor of vulnerability. With older people, many events may constitute a trauma because of the proximity of death and because of their sudden onset (fall, hospitalisation, somatic illness). Several studies have pointed out that a particularly traumatic event could enhance the risk of dementia. Life events associated with chronic or repeated stress are characterized by their permanence or their repetition. According to a general psychosomatic biological pattern, psychic distress will engender a series of degradations or an acute or chronic response to an early trauma. According to this hypothesis, prolonged exposure to an excess of glucocorticosteroids at the time of a disadaptative stress would have deleterious effects on the hippocampus. Indeed, the hippocampus plays a part in a number of functions affected by dementia such as memory, learning process and emotional adjustment. This study takes into account stress factors ("stressors") but not factors influencing their impact on the subject such as an individual predisposition (genetic, psychopathologic, coping abilities) and social support. The force of the impact of these events on older people and what is really experienced by them remain unknown. This study strengthens a number of others evincing an unusual frequency of life events in dementia processes. According to an integrative pattern, repeated or prolonged stress could be a deciding factor in the degenerative process or a factor of decompensation with older people presenting a genetic, biological or psychological vulnerability to dementia. The impact of such life events would vary according to the subject's pre-morbid personality, coping abilities and the support he/she can rely on. CONCLUSION: Some life events may be involved in the dementia process as shown by the results of this study, but this relationship does not imply direct causality. It's difficult to appreciate whether these results are not a consequence of the greater attention paid to the patient after the appearance of the first symptoms, leading to a closer observation. Stress could trigger the degenerative process. This argues for the necessity of an early diagnosis taking into account a traumatic event of life either precocious or late.

[Epilepsy and personality study among the Tamberma of Togo based on a general population survey using the Cloninger's Temperament and Character Inventory]. / Epilepsie et étude de la personnalité chez les Tambermas du Togo: à partir d'une enquête en population générale à l'aide de l'inventaire de tempérament et de caractère de Cloninger.

INTRODUCTION: There are many studies focusing on personality disorders of the patients with epilepsy in developed countries, using different methods. Such investigations with standardised tools like personality questionnaires lack in African populations in general and among the number of epileptic patients who have important psychosocial problems. In Togo, epilepsy still remains a shameful and contagious disease that leads often unfortunately to a "social death". The number of epileptic patients in this country is estimated around 45,000 and 90,000 and the situation is worst in some areas of the country like in Nadoba, chef-lieu of the Tamberma region where lives an homogenous and stable population that has kept its tradition. DESIGN OF THE STUDY: This study was aimed to show the probable existence of specific personality disorder among the epileptics in Nadoba; 34 epileptics and 34 controls chosen among the closest relatives (parents or co-tenants) matched by age (more or less than ten years old) and sex have been interviewed using the Temperament and Character Inventory (TCI) of Cloninger et al., in its French version validated by Pélissolo and Lépine. The TCI is a self addressed questionnaire that has 226 items with dichotomous and forced answer (true or false) that explores 7 dimensions of personality, 4 concerning temperament and 3 concerning character. Regarding psychometric aspects, the TCI has the particularity to gather together, in a unique tool, the exploration of two complementary dimensions: temperament rather conditional and character that has been acquired. The scores of character allow to differentiate the subjects having a good level of adaptation (high scores, about 100%), from those who, because of an individual fragility, adapt themselves less well (low scores). The temperament profile is used on a second approach to locate the personality disorders, taking into account probable deviations. People participating in this study were also interviewed with the Goldberg anxiety and depression scale. For the statistical analysis, the comparison of means was achieved through bilateral Student't-test. A significance threshold of 0.05 has been used for the analysis. RESULTS: Concerning the results, 67 questionnaires have been selected from 33 epileptics (3 men and 30 women), mean age 29.3 years+/-8.1 and 34 controls (4 men and 30 women), mean age 30.6 years+/-5.6. The average scores obtained from the different items of the TCI scale are summarised in chart 1. The comparison of average scores obtained at each item, sub-dimension and dimension of the TCI, did not show any significant difference between cases and controls. However cases were significantly different from controls (P<0.001) on average Goldberg's anxiety scores (4.6+/-1.5 and 2.6+/-1.3) and depression (4.4+/-2.2 and 0.8+/-0.8). DISCUSSION: The average scores obtained in France in the course of the normative study in general population were rather different. The validation study of the French version of TCI showed differences with the population of North America, suggesting inter cultural differences while evaluating the personality and the necessity of using specific norms during each new translation of the instrument. However, the valued in the French-speaking populations (Belgium, Swiss, Lebanon) are in general very close to the French values. The character and behavioural disorders among are of interest and the difficulty in evaluating the part of hysteria in the manifestation of exhibiting pseudo-seizure of epilepsy is also underlined. This question is raised in Nadoba in women, called "Odueri" or "the women that fall", a particular form of tonico-clonic fits observed in that cultural setting. Is it a question of real epileptic seizure or are these phenomena a kind of trance? This investigation of the Tamberma in Togo urges to set up psychometric studies to define local norms. It also suggests the possible existence of personality traits specific to the "women that fall" but these aspects require further developments.

Phosphorylation of human progesterone receptor by cyclin-dependent kinase 2 on three sites that are authentic basal phosphorylation sites in vivo.

The human progesterone receptor (hPR) in T47D breast cancer cells is phosphorylated on at least nine different serine residues. We have previously reported the identification of five sites; three are hormone inducible (Ser102, Ser294 and Ser345), and their phosphorylation correlates with the timing of the change in receptor mobility on gel electrophoresis in response to hormone treatment. The other two sites, Ser81 and Ser162, along with the remaining sites, are basally phosphorylated and exhibit a general increase in phosphorylation in response to hormone. With the exception of Ser81, all of these sites are in Ser-Pro motifs, suggesting that proline-directed kinases are responsible for their phosphorylation. We now report that cyclin A-cyclin-dependent kinase-2 complexes phosphorylate hPR-B in vitro with a high stoichiometry on three sites that are authentic basal sites in vivo. One of these is Ser162, which has been described previously. The other two sites are identified here as Ser190 and Ser400. The specificity and stoichiometry of the in vitro phosphorylation suggest that hPR phosphorylation may be regulated in a cell cycle-dependent manner in vivo.