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1.
Psychol Med ; 46(10): 2071-81, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-27094404

RESUMEN

BACKGROUND: Patients with psychosis display the so-called 'Jumping to Conclusions' bias (JTC) - a tendency for hasty decision-making in probabilistic reasoning tasks. So far, only a few studies have evaluated the JTC bias in 'at-risk mental state' (ARMS) patients, specifically in ARMS samples fulfilling 'ultra-high risk' (UHR) criteria, thus not allowing for comparisons between different ARMS subgroups. METHOD: In the framework of the PREVENT (secondary prevention of schizophrenia) study, a JTC task was applied to 188 patients either fulfilling UHR criteria or presenting with cognitive basic symptoms (BS). Similar data were available for 30 healthy control participants matched for age, gender, education and premorbid verbal intelligence. ARMS patients were identified by the Structured Interview for Prodromal Symptoms (SIPS) and the Schizophrenia Proneness Instrument - Adult Version (SPI-A). RESULTS: The mean number of draws to decision (DTD) significantly differed between ARM -subgroups: UHR patients made significantly less draws to make a decision than ARMS patients with only cognitive BS. Furthermore, UHR patients tended to fulfil behavioural criteria for JTC more often than BS patients. In a secondary analysis, ARMS patients were much hastier in their decision-making than controls. In patients, DTD was moderately associated with positive and negative symptoms as well as disorganization and excitement. CONCLUSIONS: Our data indicate an enhanced JTC bias in the UHR group compared to ARMS patients with only cognitive BS. This underscores the importance of reasoning deficits within cognitive theories of the developing psychosis. Interactions with the liability to psychotic transitions and therapeutic interventions should be unravelled in longitudinal studies.


Asunto(s)
Disfunción Cognitiva/fisiopatología , Toma de Decisiones/fisiología , Esquizofrenia/fisiopatología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Riesgo , Adulto Joven
2.
Neuroimage ; 123: 200-11, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26254112

RESUMEN

Historically, the human frontal pole (FP) has been considered as a single architectonic area. Brodmann's area 10 is located in the frontal lobe with known contributions in the execution of various higher order cognitive processes. However, recent cytoarchitectural studies of the FP in humans have shown that this portion of cortex contains two distinct cytoarchitectonic regions. Since architectonic differences are accompanied by differential connectivity and functions, the frontal pole qualifies as a candidate region for exploratory parcellation into functionally discrete sub-regions. We investigated whether this functional heterogeneity is reflected in distinct segregations within cytoarchitectonically defined FP-areas using meta-analytic co-activation based parcellation (CBP). The CBP method examined the co-activation patterns of all voxels within the FP as reported in functional neuroimaging studies archived in the BrainMap database. Voxels within the FP were subsequently clustered into sub-regions based on the similarity of their respective meta-analytically derived co-activation maps. Performing this CBP analysis on the FP via k-means clustering produced a distinct 3-cluster parcellation for each hemisphere corresponding to previously identified cytoarchitectural differences. Post-hoc functional characterization of clusters via BrainMap metadata revealed that lateral regions of the FP mapped to memory and emotion domains, while the dorso- and ventromedial clusters were associated broadly with emotion and social cognition processes. Furthermore, the dorsomedial regions contain an emphasis on theory of mind and affective related paradigms whereas ventromedial regions couple with reward tasks. Results from this study support previous segregations of the FP and provide meta-analytic contributions to the ongoing discussion of elucidating functional architecture within human FP.


Asunto(s)
Lóbulo Frontal/anatomía & histología , Lóbulo Frontal/fisiología , Algoritmos , Encéfalo/anatomía & histología , Encéfalo/fisiología , Mapeo Encefálico/métodos , Análisis por Conglomerados , Cognición/fisiología , Emociones/fisiología , Humanos , Imagen por Resonancia Magnética/métodos , Vías Nerviosas/anatomía & histología , Vías Nerviosas/fisiología , Tomografía de Emisión de Positrones/métodos
3.
Acta Psychiatr Scand ; 130(3): 214-26, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24571191

RESUMEN

OBJECTIVE: Obsessive-compulsive symptoms (OCS) constitute a major comorbidity in schizophrenia. Prevalence estimations of OCS for patients with at-risk mental states (ARMS) for psychosis vary largely. It is unclear how ARMS patients with or without comorbid OCS differ regarding general psychosocial functioning, psychotic and affective symptoms and neurocognitive abilities. METHOD: At-risk mental states patients (n = 233) from the interventional trial PREVENT (Secondary Prevention of Schizophrenia) were stratified according to the presence or absence of comorbid OCS and compared on several clinical variables. RESULTS: Patients, who fulfilled the criteria for obsessive-compulsive disorder (OCD) or presented with subclinical OCS (ARMSposOCS sample), did not significantly differ from patients without OCS (ARMSnegOCS) with regard to gender, age, premorbid verbal intelligence and levels of education. Furthermore, similar severity of depressive syndromes, basic cognitive, attenuated psychotic and brief limited intermittent psychotic symptoms were found. However, ARMSposOCS patients showed more impairment of psychosocial functioning and higher general psychopathology. In contrast, they scored higher in cognitive tasks measuring working memory and immediate verbal memory. CONCLUSION: Findings extend upon previous results due to the multidimensional assessment. Subsequent longitudinal studies might elucidate how comorbid OCS influence differential treatment response, especially to cognitive behavioural interventions and the transition rates to psychosis.


Asunto(s)
Trastorno Obsesivo Compulsivo/diagnóstico , Trastornos Psicóticos/diagnóstico , Esquizofrenia/diagnóstico , Adulto , Comorbilidad , Femenino , Humanos , Masculino , Memoria a Corto Plazo/fisiología , Recuerdo Mental/fisiología , Trastorno Obsesivo Compulsivo/epidemiología , Trastorno Obsesivo Compulsivo/fisiopatología , Síntomas Prodrómicos , Trastornos Psicóticos/epidemiología , Trastornos Psicóticos/fisiopatología , Riesgo , Esquizofrenia/epidemiología , Esquizofrenia/fisiopatología , Índice de Severidad de la Enfermedad , Adulto Joven
4.
Acta Psychiatr Scand ; 127(6): 474-81, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22957829

RESUMEN

OBJECTIVE: To evaluate the predictive validity of early response in first-episode schizophrenia within a 1-year follow-up trial and to compare the resulting cutoff to the currently proposed early response definition (20% improvement by week 2). METHOD: Receiver operator characteristic (ROC) analyses were used to identify the predictive validity of the psychopathological improvement of treatment from week 1 to week 8, regarding the maintenance of response until week 52 as well as to define the most reasonable cutoff in 132 first-episode patients. The Youden Index (maximum of sensitivity and specificity) was used to compare the newly developed and the commonly used early response definition. RESULTS: Starting with week 6, a reasonable validity to predict the maintenance of response was found (area under the curve = 0.721) with the best fitting cutoff being a 51.6% PANSS total score improvement. Using this cutoff 74 patients (56%) were correctly identified to become responder and maintain response during follow-up (sensitivity: 0.747). The Youden Index was higher applying the newly developed early response cutoff featuring higher specificity compared to the commonly used early response definition. CONCLUSION: Regarding long-term treatment, it seems more appropriate to base predictions of the patient's maintenance of response not before 6 weeks of treatment.


Asunto(s)
Antipsicóticos/uso terapéutico , Haloperidol/uso terapéutico , Risperidona/uso terapéutico , Esquizofrenia/tratamiento farmacológico , Adulto , Progresión de la Enfermedad , Método Doble Ciego , Femenino , Humanos , Estudios Longitudinales , Masculino , Curva ROC , Esquizofrenia/diagnóstico , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
5.
Health Educ Res ; 28(4): 574-90, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23669214

RESUMEN

AIDS clinical trials (ACTs) are critical to the development of new treatments for HIV infection. However, people of color living with HIV/AIDS are involved in ACTs at disproportionally low rates, with African-Americans experiencing the greatest under-representation. In this article, we describe the core elements and key characteristics of a highly efficacious multi-component peer-driven intervention (PDI) designed to increase rates of screening for and enrollment into ACTs among African-American and Latino/Hispanic individuals, by addressing the main complex, multi-level barriers they experience to ACTs. We discuss the process of developing the intervention, the theoretical models guiding its delivery format and content, and provide an overview of the intervention's components. We then use brief case studies to illustrate a number of key issues that may arise during intervention implementation. Finally, we describe lessons learned and provide recommendations for the PDI's uptake in clinical and clinical trials settings.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Negro o Afroamericano/psicología , Ensayos Clínicos como Asunto/psicología , Conocimientos, Actitudes y Práctica en Salud/etnología , Hispánicos o Latinos/psicología , Selección de Paciente , Síndrome de Inmunodeficiencia Adquirida/diagnóstico , Síndrome de Inmunodeficiencia Adquirida/etnología , Negro o Afroamericano/educación , Negro o Afroamericano/estadística & datos numéricos , Actitud del Personal de Salud , Ensayos Clínicos como Asunto/normas , Ensayos Clínicos como Asunto/estadística & datos numéricos , Miedo/psicología , Femenino , Hispánicos o Latinos/educación , Hispánicos o Latinos/estadística & datos numéricos , Humanos , Masculino , Tamizaje Masivo/psicología , Educación del Paciente como Asunto/métodos , Navegación de Pacientes/métodos , Navegación de Pacientes/organización & administración , Grupo Paritario , Sesgo de Selección , Confianza/psicología
6.
Z Gerontol Geriatr ; 46(1): 21-6, 2013 Jan.
Artículo en Alemán | MEDLINE | ID: mdl-23283402

RESUMEN

BACKGROUND: Most older adults wish to stay in their own homes even after the onset of care dependency, which is enabled by different care arrangements. General life satisfaction can serve as a criterion for assessing the functionality of these arrangements. METHODS: The study is based on a standardized survey (face-to-face interviews; n=712) performed in 2009/2010. The population consisted of persons aged ≥70 years, with a need for care, living in one of three selected Swiss German-speaking cantons. The dataset is a representative sample of the population. RESULTS: The following results were found with regard to the surveyed target group of persons aged ≥70 years, living at home and receiving formal and/or informal care: the need for care of persons ≥80 is not greater than that of persons aged 70-79 years and is not decisive for general life satisfaction. Strength of social network, presence (or absence) of pain, and satisfaction with care are more important. The odds of being satisfied with life are greater with increasing age. The social network of persons ≥80 is weaker than that of persons aged 70-79 years but contributes nonetheless to satisfaction with life.


Asunto(s)
Cuidado en Custodia/estadística & datos numéricos , Servicios de Atención de Salud a Domicilio/estadística & datos numéricos , Satisfacción del Paciente/estadística & datos numéricos , Calidad de Vida , Distribución por Edad , Anciano , Anciano de 80 o más Años , Femenino , Alemania , Humanos , Masculino , Distribución por Sexo , Encuestas y Cuestionarios , Suiza/epidemiología
7.
Diabetologia ; 55(2): 372-81, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22038519

RESUMEN

AIMS/HYPOTHESIS: In adult human islets, insulin and glucagon production is largely restricted to individual cell populations. The production of these hormones is less segregated during development and during the differentiation of human pluripotent stem cells towards pancreatic lineages. We therefore sought to characterise the transcription factor profile of these cells that co-produce insulin and glucagon in the developing human pancreas, and thus to gain insight into their potential fate during normal pancreas development. METHODS: An immunohistochemical analysis was performed on human pancreas sections from fetal donors aged 9 to 21 weeks and from adult donors between the ages of 17 and 55 years. RESULTS: Endocrine cells were observed within the pancreas at all ages examined, with cells co-producing insulin and glucagon observed as early as 9 weeks of fetal age. The population of cells that co-produce insulin and glucagon generally decreased in prevalence with age, with negligible numbers in adult pancreas. From 9 to 16 weeks, the population of glucagon-only cells increased, while the insulin-only cells decreased in abundance. Cells that co-produced insulin and glucagon also produced the alpha cell transcription factor, aristaless related homeobox (ARX), and lacked the beta cell transcription factors pancreatic and duodenal homeobox 1 (PDX1), NK6 homeobox 1 (NKX6.1) and v-maf musculoaponeurotic fibrosarcoma oncogene homologue A (MAFA). CONCLUSIONS/INTERPRETATION: Our results indicate that cells co-producing insulin and glucagon in the developing human pancreas share a transcription factor profile that is similar to that of mature alpha cells and suggest that some maturing alpha cells briefly exhibit ectopic insulin expression. Thus cells that co-produce insulin and glucagon may represent a transient cell population, which gives rise to mature alpha cells.


Asunto(s)
Glucagón/metabolismo , Inmunohistoquímica/métodos , Insulina/metabolismo , Páncreas/metabolismo , Adolescente , Adulto , Animales , Apoptosis , Proliferación Celular , Humanos , Procesamiento de Imagen Asistido por Computador , Ratones , Microscopía Fluorescente/métodos , Persona de Mediana Edad , Células Madre Pluripotentes/citología , Factores de Tiempo
8.
Gene Ther ; 19(8): 791-9, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22089495

RESUMEN

Type-I diabetes is a chronic disease mediated by autoimmune destruction of insulin-producing ß-cells. Although progress has been made towards improving diabetes-associated pathologies and the quality of life for those living with diabetes, no therapy has been effective at eliminating disease manifestations or reversing disease progression. Here, we examined whether double-stranded adeno-associated virus serotype 8 (dsAAV8)-mediated gene delivery to endogenous ß-cells of interleukin (IL)-4 in combination with ß-cell growth factors can reverse early-onset diabetes in NOD mice. Our results demonstrate that a single treatment with dsAAV8 vectors expressing IL-4 in combination with glucagon-like peptide-1 or hepatocyte growth factor/NK1 under the regulation of the insulin promoter enhanced ß-cell proliferation and survival in vivo, significantly delaying diabetes progression in NOD mice, and reversing disease in ∼10% of treated NOD mice. These results demonstrate the ability to reverse hyperglycemia in NOD mice with established diabetes by in vivo gene transfer to ß-cells of immunomodulatory factors and ß-cell growth factors.


Asunto(s)
Dependovirus/genética , Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Tipo 1/terapia , Terapia Genética , Péptido 1 Similar al Glucagón/genética , Factor de Crecimiento de Hepatocito/genética , Células Secretoras de Insulina/metabolismo , Interleucina-4/genética , Animales , Diabetes Mellitus Tipo 1/genética , Femenino , Técnicas de Transferencia de Gen , Vectores Genéticos , Péptido 1 Similar al Glucagón/metabolismo , Factor de Crecimiento de Hepatocito/metabolismo , Interleucina-4/metabolismo , Ratones , Ratones Endogámicos NOD
9.
Pharmacopsychiatry ; 45(7): 292-6, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22614116

RESUMEN

Akathisia as well as younger age, early illness onset and discharge are important risk factors for suicidality in patients with first-episode schizophrenia. The aim of the present study was to analyze on a single case basis the relationship between a sudden increase in suicidality, anxiety symptoms, medication dosing and clinician- and patient-rated akathisia. A small subsample of patients demonstrated a positive relationship between suicidality and akathisia scores within the titration period of the study medication.


Asunto(s)
Acatisia Inducida por Medicamentos/psicología , Haloperidol/efectos adversos , Risperidona/efectos adversos , Esquizofrenia/tratamiento farmacológico , Psicología del Esquizofrénico , Ideación Suicida , Adolescente , Adulto , Factores de Edad , Antipsicóticos/efectos adversos , Antipsicóticos/uso terapéutico , Ansiedad/inducido químicamente , Femenino , Haloperidol/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica/estadística & datos numéricos , Factores de Riesgo , Risperidona/uso terapéutico
10.
Appl Environ Microbiol ; 77(19): 6780-7, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21821755

RESUMEN

Methane release from seafloor sediments is moderated, in part, by the anaerobic oxidation of methane (AOM) performed by consortia of archaea and bacteria. These consortia occur as isolated cells and aggregates within the sulfate-methane transition (SMT) of diffusion and seep-dominant environments. Here we report on a new SMT setting where the AOM consortium occurs as macroscopic pink to orange biofilms within subseafloor fractures. Biofilm samples recovered from the Indian and northeast Pacific Oceans had a cellular abundance of 10(7) to 10(8) cells cm(-3). This cell density is 2 to 3 orders of magnitude greater than that in the surrounding sediments. Sequencing of bacterial 16S rRNA genes indicated that the bacterial component is dominated by Deltaproteobacteria, candidate division WS3, and Chloroflexi, representing 46%, 15%, and 10% of clones, respectively. In addition, major archaeal taxa found in the biofilm were related to the ANME-1 clade, Thermoplasmatales, and Desulfurococcales, representing 73%, 11%, and 10% of archaeal clones, respectively. The sequences of all major taxa were similar to sequences previously reported from cold seep environments. PhyloChip microarray analysis detected all bacterial phyla identified by the clone library plus an additional 44 phyla. However, sequencing detected more archaea than the PhyloChip within the phyla of Methanosarcinales and Desulfurococcales. The stable carbon isotope composition of the biofilm from the SMT (-35 to -43‰) suggests that the production of the biofilm is associated with AOM. These biofilms are a novel, but apparently widespread, aggregation of cells represented by the ANME-1 clade that occur in methane-rich marine sediments.


Asunto(s)
Archaea/metabolismo , Bacterias/metabolismo , Biopelículas/crecimiento & desarrollo , Sedimentos Geológicos/microbiología , Metano/metabolismo , Consorcios Microbianos/fisiología , Anaerobiosis , Archaea/clasificación , Archaea/aislamiento & purificación , Bacterias/clasificación , Bacterias/aislamiento & purificación , Análisis por Conglomerados , ADN de Archaea/química , ADN de Archaea/genética , ADN Bacteriano/química , ADN Bacteriano/genética , ADN Ribosómico/química , ADN Ribosómico/genética , Genes de ARNr , Datos de Secuencia Molecular , Oxidación-Reducción , Océano Pacífico , Filogenia , ARN de Archaea/genética , ARN Bacteriano/genética , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Homología de Secuencia de Ácido Nucleico , Sulfatos/metabolismo
11.
Acta Psychiatr Scand ; 123(3): 228-38, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21029053

RESUMEN

OBJECTIVE: To examine depressive symptoms, their course during treatment, and influence on outcome. METHOD: Weekly Calgary Depression Scale for Schizophrenia ratings were performed in 249 inpatients with schizophrenia. Early response was defined as a 20% reduction in the total score of the Positive and Negative Syndrome Scale for Schizophrenia from admission to week 2, response as a 50% reduction in the total score of the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) from admission to discharge and remission according to the consensus criteria. RESULTS: Thirty six per cent of the patients were depressed at admission, with 23% of them still being depressed at discharge. Depressed patients scored significantly higher on the PANSS negative and general psychopathology subscore, featured more impairments in subjective well-being (P < 0.0001) and functioning (P < 0.0001). They suffered from more suicidality (P = 0.0021), and had greater insight into their illness (P = 0.0105). No significant differences were found regarding early response, response, and remission. CONCLUSION: Patients with depressive symptoms should be monitored closely, given the burden of negative symptoms, their impairments in well-being and functioning and the threat of suicidality.


Asunto(s)
Depresión/psicología , Escalas de Valoración Psiquiátrica , Psicología del Esquizofrénico , Adulto , Factores de Edad , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Humanos , Estimación de Kaplan-Meier , Modelos Logísticos , Masculino , Esquizofrenia/terapia , Ideación Suicida , Factores de Tiempo , Resultado del Tratamiento
12.
Clin Nephrol ; 75(4): 302-8, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21426884

RESUMEN

BACKGROUND: The purpose of this study was to examine the efficacy of sodium 2-mercaptoethanesulfonate (MESNA), a reactive oxygen scavenger, in at-risk patients given radiographic contrast agents. Contrast-induced nephropathy (CIN) is a common complication of radiographic procedures; reactive oxygen species (ROS) could play a key role. METHODS: We conducted a randomized, double-blinded, placebo-controlled trial in 100 patients with stable serum creatinine levels ≥ 150 µmol/l. They received an infusion of either 1,600 mg of MESNA (n = 51) or placebo (n = 49) plus 0.9% saline prior to and after contrast administration. CIN was defined as a ≥ 25% increase in serum creatinine after 48 h compared to baseline. RESULTS: CIN occurred in 7 patients in the placebo group and none in the MESNA group (p = 0.005). The adjusted odds ratio for CIN was 0.17 (95% confidence interval 0.03 - 0.80, p = 0.026) in the MESNA group compared to the placebo group. Cystatin C concentrations decreased slightly in the MESNA group but increased in the control group (p < 0.05). CONCLUSION: MESNA plus volume expansion before and during contrast exposure was effective in this single-center study for preventing CIN compared to volume expansion alone.


Asunto(s)
Medios de Contraste/efectos adversos , Enfermedades Renales/inducido químicamente , Enfermedades Renales/prevención & control , Mesna/uso terapéutico , Sustancias Protectoras/uso terapéutico , Anciano , Método Doble Ciego , Femenino , Humanos , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Placebos , Estadísticas no Paramétricas , Resultado del Tratamiento
13.
Qual Life Res ; 20(2): 263-72, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20922485

RESUMEN

PURPOSE: To develop and evaluate a self- and observer-rating scale on quality of life in patients suffering from schizophrenia with regard to the efficacy of atypical antipsychotics based on different dimensions and to apply within a pilot study. METHODS: Following review of existing scales and a prevalidation phase, the Riedel-Spellmann-Musil (RSM) scale was developed comprising 36 items assigned to different subscales. As reference scales, the Quality of Life Scale (QLS) and the Subjective Well-being Under Neuroleptic Treatment Scale-short version (SWN-K) were performed, psychopathology and adverse events were measured at all visits. Reliability was assessed using Cronbach's alpha, Pearson's correlation coefficients were used to assess construct validity, and Intraclass Correlation Coefficients (ICCs) were used for test-retest reliability. T tests were performed in normal distributed samples; otherwise Wilcoxon tests were used. RESULTS: One hundred and thirty-six patients were included in the study. Cronbach`s α was 0.917 for the self-rating and 0.915 for the interviewer-rating part. ICCs were >0.70 for all subscales. The self-rating part correlated strongly with the SWN-K and the observer part with the QLS. Changes in psychopathology over the study period and different levels of functioning were detected. CONCLUSION: The RSM-scale is a new scale to assess the quality of life in different dimensions of patients with schizophrenia treated with antipsychotics and shows good internal consistency, test-retest reliability, construct and discriminant validity.


Asunto(s)
Antipsicóticos/uso terapéutico , Calidad de Vida , Esquizofrenia , Índice de Severidad de la Enfermedad , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Observación , Proyectos Piloto , Reproducibilidad de los Resultados , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/fisiopatología , Encuestas y Cuestionarios , Resultado del Tratamiento
14.
Pharmacopsychiatry ; 44(1): 27-32, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20981642

RESUMEN

INTRODUCTION: Assessment of depression severity is of key importance, since several clinical guidelines recommend choice of treatment dependent on the depression severity grade. Using different tools to assess baseline severity may result in different outcomes. METHODS: This paper describes the results of a multicentre, naturalistic study investigating the relationship between depression symptom severity (using 4 different measures of symptom severity) and clinical outcome among patients hospitalised for depression (N=1 014). Moreover, the impact of differences between methods of measuring depression severity has been investigated. Statistical analyses (univariate measurements, logistic regression models) were conducted to detect coherences and differences between the various methods of severity categorisation. RESULTS: Results revealed different associations between outcome and classification methods. Response or remission rates varied if baseline severity was assessed by different instruments. Moreover, the number of responders increased with higher baseline severity grades of depression, whereas the number of remitters decreased. Additional analyses dependent on outcome criteria using continuous instead of categorical data revealed similar results. DISCUSSION: Baseline severity may be only one of many other important clinical variables that mediate clinical outcome, but it is surely an important one deserving further research and consideration.


Asunto(s)
Antidepresivos/uso terapéutico , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/psicología , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Escalas de Valoración Psiquiátrica , Índice de Severidad de la Enfermedad , Factores Sexuales , Resultado del Tratamiento
15.
Gene Ther ; 17(2): 171-80, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19865180

RESUMEN

Glucagon-like peptide-1 (GLP-1) is an incretin hormone that performs a wide array of well-characterized antidiabetic actions, including stimulation of glucose-dependent insulin secretion, upregulation of insulin gene expression and improvements in beta-cell survival. GLP-1-receptor agonists have been developed for treatment of diabetes; however, the short biological half-lives of these peptide-based therapeutics requires that frequent injections be administered to maintain sufficient circulating levels. Thus, novel methods of delivering GLP-1 remain an important avenue of active research. It has recently been demonstrated that self-complimentary, double-stranded, adeno-associated virus serotype-8 (DsAAV8) can efficiently transduce pancreatic beta-cells in vivo, resulting in long-term transgene expression. In this study, we engineered a DsAAV8 vector containing a GLP-1 transgene driven by the mouse insulin-II promoter (MIP). Biological activity of the GLP-1 produced from this transgene was assessed using a luciferase-based bioassay. DsAAV8-MIP-GLP-1 was delivered via intraperitoneal injection and beta-cell damage induced by multiple low dose streptozotocin (STZ) administration. Glucose tolerance was assessed following intraperitoneal glucose injections and beta-cell proliferation measured by PCNA expression. Expression of GLP-1 in Min6 beta-cells resulted in glucose-dependent secretion of biologically active GLP-1. Intraperitoneal delivery of DsAAV8-MIP-GLP-1 to mice led to localized GLP-1 expression in beta-cells and protection against development of diabetes induced by multiple low-dose STZ administration. This protection was associated with significant increase in beta-cell proliferation. Results from this study indicate that expression and secretion of GLP-1 from beta-cells in vivo via DsAAV8 represents a novel therapeutic strategy for treatment of diabetes.


Asunto(s)
Dependovirus/genética , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/prevención & control , Terapia Genética/métodos , Vectores Genéticos , Péptido 1 Similar al Glucagón/genética , Células Secretoras de Insulina/metabolismo , Animales , Proliferación Celular , Péptido 1 Similar al Glucagón/metabolismo , Inyecciones Intraperitoneales , Insulina/genética , Ratones , Ratones Endogámicos BALB C , Regiones Promotoras Genéticas
16.
J Exp Biol ; 213(Pt 7): 1115-25, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20228348

RESUMEN

Pitcher plants of the genus Nepenthes efficiently trap and retain insect prey in highly specialized leaves. Besides a slippery peristome which inhibits adhesion of insects they employ epicuticular wax crystals on the inner walls of the conductive zone of the pitchers to hamper insect attachment by adhesive devices. It has been proposed that the detachment of individual crystals and the resulting contamination of adhesive organs is responsible for capturing insects. However, our results provide evidence in favour of a different mechanism, mainly based on the stability and the roughness of the waxy surface. First, we were unable to detect a large quantity of crystal fragments on the pads of insects detached from mature pitcher surfaces of Nepenthes alata. Second, investigation of the pitcher surface by focused ion beam treatment showed that the wax crystals form a compact 3D structure. Third, atomic force microscopy of the platelet-shaped crystals revealed that the crystals are mechanically stable, rendering crystal detachment by insect pads unlikely. Fourth, the surface profile parameters of the wax layer showed striking similarities to those of polishing paper with low grain size. By measuring friction forces of insects on this artificial surface we demonstrate that microscopic roughness alone is sufficient to minimize insect attachment. A theoretical model shows that surface roughness within a certain length scale will prevent adhesion by being too rough for adhesive pads but not rough enough for claws.


Asunto(s)
Insectos/fisiología , Sarraceniaceae/anatomía & histología , Sarraceniaceae/parasitología , Ceras/química , Adhesividad , Animales , Cristalización , Femenino , Insectos/ultraestructura , Microscopía de Fuerza Atómica , Modelos Biológicos , Sarraceniaceae/ultraestructura , Propiedades de Superficie
17.
Acta Psychiatr Scand ; 121(5): 359-70, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-19878135

RESUMEN

OBJECTIVE: Purpose was to assess suicidality before and at the time of admission in patients with schizophrenia and compare outcome differences. METHOD: Biweekly PANSS (Positive and Negative Syndrome Scale), HAMD (Hamilton Depression Rating Scale) and UKU (Udvalg for Klinske Undersogelser Side Effect Rating Scale) ratings were evaluated in 339 in-patients with schizophrenic spectrum disorders. Response was defined as an initial 20% PANSS total score reduction at discharge, remission was defined according to the proposed consensus criteria by the Remission in Schizophrenia Working Group. RESULTS: Suicidal patients (22%) scored significantly higher on the PANSS negative subscore, PANSS insight item and HAMD total score at admission and at discharge. They developed significantly more side effects. No differences were found concerning response and remission between the two patient subgroups. CONCLUSION: Despite receiving significantly more antidepressants the suicidal patients suffered from significantly more depressive symptoms up to discharge, yet without differing regarding response and remission.


Asunto(s)
Esquizofrenia/epidemiología , Psicología del Esquizofrénico , Intento de Suicidio/psicología , Intento de Suicidio/estadística & datos numéricos , Enfermedad Aguda , Adulto , Acatisia Inducida por Medicamentos/diagnóstico , Acatisia Inducida por Medicamentos/epidemiología , Acatisia Inducida por Medicamentos/psicología , Antipsicóticos/efectos adversos , Antipsicóticos/uso terapéutico , Estudios de Cohortes , Comorbilidad , Estudios Transversales , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/epidemiología , Trastorno Depresivo Mayor/psicología , Femenino , Alemania , Encuestas Epidemiológicas , Hospitales Universitarios , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Factores de Riesgo , Esquizofrenia/diagnóstico , Resultado del Tratamiento , Adulto Joven
18.
Nature ; 430(6998): 439-41, 2004 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-15269764

RESUMEN

The electronic properties of many materials can be controlled by introducing appropriate impurities into the bulk crystal lattice in a process known as doping. In this way, diamond (a well-known insulator) can be transformed into a semiconductor, and recent progress in thin-film diamond synthesis has sparked interest in the potential applications of semiconducting diamond. However, the high dopant activation energies (in excess of 0.36 eV) and the limitation of donor incorporation to (111) growth facets only have hampered the development of diamond-based devices. Here we report a doping mechanism for diamond, using a method that does not require the introduction of foreign atoms into the diamond lattice. Instead, C60 molecules are evaporated onto the hydrogen-terminated diamond surface, where they induce a subsurface hole accumulation and a significant rise in two-dimensional conductivity. Our observations bear a resemblance to the so-called surface conductivity of diamond seen when hydrogenated diamond surfaces are exposed to air, and support an electrochemical model in which the reduction of hydrated protons in an aqueous surface layer gives rise to a hole accumulation layer. We expect that transfer doping by C60 will open a broad vista of possible semiconductor applications for diamond.

19.
Hum Psychopharmacol ; 25(2): 116-25, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20196179

RESUMEN

BACKGROUND: To examine influencing variables of neurocognition in patients with schizophrenia and to predict cognition during antipsychotic treatment. METHODS: Data were obtained from patients with an acute episode of schizophrenia participating in two double-blind and one open label trial comparing the effects of different atypical antipsychotics on cognition. In total, 129 patients were enrolled in this analysis. Cognitive function was assessed at admission, week 4 and 8. Efficacy and tolerability were assessed weekly using the Positive and Negative Syndrome Scale (PANSS) and the Simpson Angus Sale (SAS). Patients were treated with aripirazole, olanzapine, quetiapine and risperidone. Regression analysis including mixed effect models was performed. RESULTS: A significant improvement in all cognitive domains was observed from baseline to week 8. Regarding the antipsychotic treatment applied quetiapine seemed to achieve the most favourable cognitive improvement. Negative and depressive symptoms, the patient's age and the concomitant and antipsychotic treatment applied were observed to significantly influence and predict neurocognition. CONCLUSION: The results may indicate that schizophrenia is a static disorder with trait and state dependent cognitive components especially in the memory domains. The influence of negative and depressive symptoms should be considered in daily clinical routine.


Asunto(s)
Antipsicóticos/uso terapéutico , Trastornos del Conocimiento/complicaciones , Cognición/efectos de los fármacos , Neuronas/efectos de los fármacos , Esquizofrenia/complicaciones , Esquizofrenia/tratamiento farmacológico , Enfermedad Aguda , Adolescente , Adulto , Anciano , Envejecimiento , Antipsicóticos/administración & dosificación , Antipsicóticos/efectos adversos , Trastornos del Conocimiento/fisiopatología , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Interacciones Farmacológicas , Humanos , Memoria/efectos de los fármacos , Trastornos de la Memoria/complicaciones , Trastornos de la Memoria/fisiopatología , Persona de Mediana Edad , Esquizofrenia/fisiopatología , Esquizofrenia/terapia , Índice de Severidad de la Enfermedad , Factores de Tiempo , Adulto Joven
20.
Pharmacopsychiatry ; 43(2): 50-7, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20336597

RESUMEN

BACKGROUND: The aim of this study was to assess the cognitive effects of aripiprazole in inpatients with schizophrenia. METHODS: This was an investigator-initiated, open label eight-week trial evaluating 56 inpatients with the DSM-IV diagnosis of schizophrenia. Efficacy was assessed weekly using the Positive and Negative Syndrome Scale (PANSS) and tolerability was assessed each week using the Udvalg for Klinske Undersogelser side effect rating scale (UKU). Cognitive function was assessed at baseline, week 4 and week 8. RESULTS: Aripiprazole showed significant improvement in PANSS total score and all subscores between baseline and endpoint visit. The substance was very well tolerated. Patients improved significantly in verbal memory, reaction time and reaction quality/attention from baseline to week eight. Furthermore, mean z-values of individual cognitive domains summarized in a global cognitive index improved significantly from baseline to week eight. DISCUSSION: Our results suggest that aripiprazole provides a valuable treatment option for patients with schizophrenia.


Asunto(s)
Antipsicóticos/uso terapéutico , Cognición/efectos de los fármacos , Piperazinas/uso terapéutico , Quinolonas/uso terapéutico , Esquizofrenia/tratamiento farmacológico , Adulto , Antipsicóticos/efectos adversos , Aripiprazol , Atención/efectos de los fármacos , Humanos , Pacientes Internos , Memoria/efectos de los fármacos , Pruebas Neuropsicológicas , Piperazinas/efectos adversos , Escalas de Valoración Psiquiátrica , Quinolonas/efectos adversos , Tiempo de Reacción/efectos de los fármacos , Factores de Tiempo , Resultado del Tratamiento
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