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1.
Mol Psychiatry ; 19(6): 724-32, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23999524

RESUMEN

Anorexia nervosa (AN) and related eating disorders are complex, multifactorial neuropsychiatric conditions with likely rare and common genetic and environmental determinants. To identify genetic variants associated with AN, we pursued a series of sequencing and genotyping studies focusing on the coding regions and upstream sequence of 152 candidate genes in a total of 1205 AN cases and 1948 controls. We identified individual variant associations in the Estrogen Receptor-ß (ESR2) gene, as well as a set of rare and common variants in the Epoxide Hydrolase 2 (EPHX2) gene, in an initial sequencing study of 261 early-onset severe AN cases and 73 controls (P=0.0004). The association of EPHX2 variants was further delineated in: (1) a pooling-based replication study involving an additional 500 AN patients and 500 controls (replication set P=0.00000016); (2) single-locus studies in a cohort of 386 previously genotyped broadly defined AN cases and 295 female population controls from the Bogalusa Heart Study (BHS) and a cohort of 58 individuals with self-reported eating disturbances and 851 controls (combined smallest single locus P<0.01). As EPHX2 is known to influence cholesterol metabolism, and AN is often associated with elevated cholesterol levels, we also investigated the association of EPHX2 variants and longitudinal body mass index (BMI) and cholesterol in BHS female and male subjects (N=229) and found evidence for a modifying effect of a subset of variants on the relationship between cholesterol and BMI (P<0.01). These findings suggest a novel association of gene variants within EPHX2 to susceptibility to AN and provide a foundation for future study of this important yet poorly understood condition.


Asunto(s)
Anorexia Nerviosa/genética , Epóxido Hidrolasas/genética , Variación Genética , Adulto , Anorexia Nerviosa/metabolismo , Índice de Masa Corporal , Estudios de Casos y Controles , Colesterol/metabolismo , Estudios de Cohortes , Femenino , Predisposición Genética a la Enfermedad , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Psicometría , Población Blanca/genética , Adulto Joven
2.
Nervenarzt ; 82(9): 1107-17, 2011 Sep.
Artículo en Alemán | MEDLINE | ID: mdl-21755336

RESUMEN

Recent technological developments of communication media offer new approaches to diagnostic and therapeutic interactions with patients. One major development is Internet-based primary prevention in vulnerable individuals not yet suffering as well as the development of new therapeutic approaches for affected individuals based on the experiences of guided self-help through CD, DVD or bibliotherapy. The eating disorder literature shows several interesting, partly controlled and randomized, studies on bulimia nervosa, a few studies on binge eating disorder and no studies on anorexia nervosa. As part of the German Eating Disorder Network on Psychotherapy (EDNET) a 9-month Internet-based relapse prevention program for patients with anorexia nervosa after inpatient treatment was evaluated. Conception, first experiences and first results of the Internet-based relapse prevention program for anorexia nervosa are reported.


Asunto(s)
Trastornos de Alimentación y de la Ingestión de Alimentos/terapia , Internet , Terapia Asistida por Computador , Adolescente , Adulto , Anorexia Nerviosa/diagnóstico , Anorexia Nerviosa/terapia , Biblioterapia , Trastorno por Atracón/diagnóstico , Trastorno por Atracón/terapia , Bulimia Nerviosa/diagnóstico , Bulimia Nerviosa/terapia , Discos Compactos , Trastornos de Alimentación y de la Ingestión de Alimentos/diagnóstico , Femenino , Humanos , Masculino , Evaluación de Procesos y Resultados en Atención de Salud , Psicoterapia/métodos , Prevención Secundaria , Autocuidado , Programas Informáticos , Grabación de Videodisco , Adulto Joven
3.
Eat Weight Disord ; 15(3): e186-9, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21150253

RESUMEN

We assessed the relation between season of birth and eating disorder symptoms and personality characteristics in a sample of 880 women with eating disorders and 580 controls from two Price Foundation Studies. Eating disorder symptoms were assessed using the Structured Interview of Anorexic and Bulimic Disorders and the Structured Clinical Interview for DSM-IV. Personality traits were assessed using the Temperament and Character Inventory and the Frost Multidimensional Perfectionism Scale. Date of birth was obtained from a sociodemographic questionnaire. No significant differences were observed 1) in season of birth across eating disorder subtypes and controls; nor 2) for any clinical or personality variables and season of birth. We found no evidence of season of birth variation in eating disorders symptoms or personality traits. Contributing to previous conflicting findings, the present results do not support a season of birth hypothesis for eating disorders.


Asunto(s)
Trastornos de Alimentación y de la Ingestión de Alimentos , Personalidad , Adolescente , Adulto , Factores de Edad , Anciano , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Trastornos de Alimentación y de la Ingestión de Alimentos/epidemiología , Trastornos de Alimentación y de la Ingestión de Alimentos/fisiopatología , Trastornos de Alimentación y de la Ingestión de Alimentos/psicología , Femenino , Humanos , Persona de Mediana Edad , Parto , Estaciones del Año , Encuestas y Cuestionarios , Adulto Joven
4.
Acta Psychiatr Scand ; 122(1): 75-85, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19922523

RESUMEN

OBJECTIVE: Assessment of 25-year course of pure and mixed anxiety and depression in a community sample. METHOD: Participants were grouped into pure anxiety, pure depression, mixed anxiety and depression, and no anxiety or depressive syndrome at baseline. Assessments consisted of a: i) baseline survey, ii) 5-year follow-up, iii) 25-year follow-up. Self-rating scales as well as expert-rating interviews yielded data on social and psychopathological risk factors and outcome measures. RESULTS: Baseline prevalence for mixed anxiety and depressive syndrome was 8.7%. Subjects with combined anxiety and depressive syndrome were more predisposed towards later adverse mental health outcomes and reduced functionality. The transition from anxiety syndrome (pure and mixed) to depressive syndrome over the 25-year study is more likely than the reverse. Logistic regression analysis emphasized the impact of early anxiety syndromes on later depression. CONCLUSION: Results underscore the long-term risks of suffering from a combined anxiety and depressive syndrome.


Asunto(s)
Trastornos de Ansiedad/epidemiología , Trastorno Depresivo/epidemiología , Salud Mental/estadística & datos numéricos , Vigilancia de la Población/métodos , Adulto , Distribución por Edad , Edad de Inicio , Anciano , Femenino , Alemania/epidemiología , Humanos , Modelos Logísticos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Prevalencia , Encuestas y Cuestionarios , Adulto Joven
5.
Int J Mol Med ; 24(5): 677-83, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19787202

RESUMEN

CD44 is a transmembrane glycoprotein involved in the interaction between cells and the extracellular matrix. A large variety of alternatively spliced CD44 variants are expressed by different tumors with possible implication for tumor progression, formation of metastasis and survival. In colon carcinomas, previous reports described higher molecular bands of CD44 transcripts in neoplastic colonic tissue, although a complete analysis of multiple combinations of CD44v transcripts were not performed. We therefore analyzed the pattern of CD44 standard and variant (v2-v10) transcripts in colorectal adenomas and carcinomas by exon-specific RT-PCR amplification and sought CD44v transcripts specific for colonic neoplasias. Our data indicate that CD44 standard transcripts, including the epithelial form (C-v8,v9,v10-C) corresponding to a 720 bp transcript, were detected in 2/38 (5.2%) samples of normal mucosa, 20/20 (100%) adenomas and in 21/33 (63%) colorectal carcinomas. High molecular CD44v3,v8-10 (673 bp) transcripts were found in 2/33 (6%) samples from normal mucosa, 19/20 (95%) from adenomas and in 29/31 from colorectal carcinomas (93%). Similar CD44v3,v8-10 transcripts were detected in five from seven colorectal liver metastases, while normal liver did not contain high molecular CD44v3 variants. The same CD44v3,v8-10 (673 bp) variant was detected in HT-29 human colon carcinoma cells. Direct sequencing of the CD44v3 (673 bp) transcript in samples from colorectal carcinomas and HT-29 cells confirmed the assumed CD44v (-C-v3-v8-v9-v10-C-) cDNA sequence. Analysis of other CD44 variant transcripts (v4-v10) using exon specific primers were less frequently associated with colorectal neoplasias. These data report for the first time frequent expression of neoplasia-associated CD44v3,v8-10 variants in colorectal adenomas and carcinomas supporting the role of increased CD44 variant expression as an early event in colorectal carcinogenesis. The described CD44v3,v8-10 (673 bp) variant might be relevant for diagnosis and treatment of colorectal cancer.


Asunto(s)
Adenoma/genética , Emparejamiento Base/genética , Neoplasias Colorrectales/genética , Regulación Neoplásica de la Expresión Génica , Receptores de Hialuranos/genética , Secuencia de Bases , Células HT29 , Humanos , Receptores de Hialuranos/metabolismo , Datos de Secuencia Molecular , Peso Molecular , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de Secuencia de ADN
6.
Int J Mol Med ; 23(5): 639-49, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19360323

RESUMEN

Initiation of cell growth and neoplastic transformation frequently involves activation of growth factor receptor-coupled tyrosine kinases and stimulation of the phosphoinositide second messenger system. Altered expression of CD44 variants was reported in several malignant tumor types with possible implications for tumor progression and prognosis. CD44 variant expression was reported to be associated with second messenger activation and differentiation. We therefore investigated the effects of butyrate-induced short-term differentiation on phosphoinositide signaling, phospholipase C and protein kinase C activity and alteration of CD44 variant expression in human HT-29 colon carcinoma cells. HT-29 cells were cultured with sodium butyrate for 6 days. Phosphoinositide turnover was measured by [32P]orthophosphate incorporation and phospholipase C activity by determination of the release of [3H]inositolphosphates from [3H]myoinositol prelabeled cells. Protein kinase C activity was determined by histone III-S phosphorylation, PKC subtype expression by RNase protection analysis, and CD44 variant expression was determined by RT-PCR using variant-specific primers. Treatment of HT-29 human colon carcinoma cells with sodium butyrate caused a dose-dependent inhibition of cell proliferation (IC50, 2.5 mM) with morphologic signs of an enterocytic differentiation following 6 days of treatment. The phosphoinositide turnover as determined by 32P-incorporation under non-equilibrium conditions showed a 30-40% inhibition of labeled phosphoinositides and phosphatidic acid and a dose-dependent inhibition of cholinergically stimulated phospholipase C activity as a secondary event following butyrate-induced enterocytic differentiation. However, long-term incubation of HT-29 cells with phorbol ester or an inhibitor of classical and novel PKC subtypes did not affect cell proliferation. In butyrate-treated HT-29 cells activation of calcium-dependent protein kinase C by cholinergic stimulation or phorbolester treatment induced an increase in membrane-bound cPKC activity, while expression of distinct high- molecular CD44 variant transcripts v3 (670 bp), v5 (940 bp) and v8 (535 bp) were drastically reduced after butyrate pretreatment. Enterocytic differentiation of HT-29 colon carcinoma cells seems to be associated with alterations in phosphoinositide resynthesis, phospholipase C activity and ligand/receptor-induced PKC translocation. The observed reduction of distinct high-molecular CD44v3, v5 and v8 variants following butyrate-induced differentiation indicates an association of specific CD44 variant expression with the malignant phenotype of HT-29 colon cancer cells, thus being possible targets for new diagnostic and therapeutic strategies.


Asunto(s)
Butiratos/farmacología , Carcinoma , Neoplasias del Colon , Receptores de Hialuranos/genética , Fosfatidilinositoles/metabolismo , Proteína Quinasa C/antagonistas & inhibidores , Carcinoma/genética , Carcinoma/metabolismo , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/genética , Proliferación Celular/efectos de los fármacos , Neoplasias del Colon/genética , Neoplasias del Colon/metabolismo , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Células HT29 , Humanos , Receptores de Hialuranos/metabolismo , Isoenzimas/genética , Isoenzimas/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Proteína Quinasa C/genética , Proteína Quinasa C/metabolismo , Transporte de Proteínas/efectos de los fármacos , Fosfolipasas de Tipo C/metabolismo
7.
Psychol Med ; 39(3): 451-61, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18578898

RESUMEN

BACKGROUND: Anorexia nervosa (AN) is associated with behavioral traits that predate the onset of AN and persist after recovery. We identified patterns of behavioral traits in AN trios (proband plus two biological parents). METHOD: A total of 433 complete trios were collected in the Price Foundation Genetic Study of AN using standardized instruments for eating disorder (ED) symptoms, anxiety, perfectionism, and temperament. We used latent profile analysis and ANOVA to identify and validate patterns of behavioral traits. RESULTS: We distinguished three classes with medium to large effect sizes by mothers' and probands' drive for thinness, body dissatisfaction, perfectionism, neuroticism, trait anxiety, and harm avoidance. Fathers did not differ significantly across classes. Classes were distinguished by degree of symptomatology rather than qualitative differences. Class 1 (approximately 33%) comprised low symptom probands and mothers with scores in the healthy range. Class 2 ( approximately 43%) included probands with marked elevations in drive for thinness, body dissatisfaction, neuroticism, trait anxiety, and harm avoidance and mothers with mild anxious/perfectionistic traits. Class 3 (approximately 24%) included probands and mothers with elevations on ED and anxious/perfectionistic traits. Mother-daughter symptom severity was related in classes 1 and 3 only. Trio profiles did not differ significantly by proband clinical status or subtype. CONCLUSIONS: A key finding is the importance of mother and daughter traits in the identification of temperament and personality patterns in families affected by AN. Mother-daughter pairs with severe ED and anxious/perfectionistic traits may represent a more homogeneous and familial variant of AN that could be of value in genetic studies.


Asunto(s)
Anorexia Nerviosa/diagnóstico , Anorexia Nerviosa/genética , Padres/psicología , Personalidad/genética , Adulto , Edad de Inicio , Anorexia Nerviosa/psicología , Imagen Corporal , Femenino , Predisposición Genética a la Enfermedad/genética , Predisposición Genética a la Enfermedad/psicología , Humanos , Masculino , Persona de Mediana Edad , Madres/psicología , Núcleo Familiar/psicología , Personalidad/clasificación , Inventario de Personalidad , Factores de Riesgo , Encuestas y Cuestionarios , Temperamento/clasificación
8.
Fetal Diagn Ther ; 23(4): 271-86, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18417993

RESUMEN

Myelomeningocele is a common dysraphic defect leading to severe impairment throughout the patient's lifetime. Although surgical closure of this anomaly is usually performed in the early postnatal period, an estimated 330 cases of intrauterine repair have been performed in a few specialized centers worldwide. It was hoped prenatal intervention would improve the prognosis of affected patients, and preliminary findings suggest a reduced incidence of shunt-dependent hydrocephalus, as well as an improvement in hindbrain herniation. However, the expectations for improved neurological outcome have not been fulfilled and not all patients benefit from fetal surgery in the same way. Therefore, a multicenter randomized controlled trial was initiated in the USA to compare intrauterine with conventional postnatal care, in order to establish the procedure-related benefits and risks. The primary study endpoints include the need for shunt at 1 year of age, and fetal and infant mortality. No data from the trial will be published before the final analysis has been completed in 2008, and until then, the number of centers offering intrauterine MMC repair in the USA is limited to 3 in order to prevent the uncontrolled proliferation of new centers offering this procedure. In future, refined, risk-reduced surgical techniques and new treatment options for preterm labor and preterm rupture of the membranes are likely to reduce associated maternal and fetal risks and improve outcome, but further research will be needed.


Asunto(s)
Procedimientos Neuroquirúrgicos/tendencias , Disrafia Espinal/cirugía , Animales , Malformación de Arnold-Chiari/diagnóstico por imagen , Malformación de Arnold-Chiari/fisiopatología , Malformación de Arnold-Chiari/cirugía , Modelos Animales de Enfermedad , Femenino , Fetoscopía/efectos adversos , Fetoscopía/tendencias , Humanos , Hidrocefalia/diagnóstico por imagen , Hidrocefalia/fisiopatología , Hidrocefalia/cirugía , Histerotomía/efectos adversos , Histerotomía/tendencias , Recién Nacido , Meningomielocele/diagnóstico por imagen , Meningomielocele/fisiopatología , Meningomielocele/cirugía , Regeneración Nerviosa , Defectos del Tubo Neural/diagnóstico por imagen , Defectos del Tubo Neural/etiología , Defectos del Tubo Neural/cirugía , Procedimientos Neuroquirúrgicos/efectos adversos , Cuidados Posoperatorios , Embarazo , Disrafia Espinal/diagnóstico por imagen , Disrafia Espinal/fisiopatología , Ultrasonografía Prenatal , Cicatrización de Heridas
9.
Zentralbl Neurochir ; 68(3): 101-10, 2007 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-17665337

RESUMEN

The severe functional deficits in patients suffering from traumatic peripheral nerve damage underline the necessity of an optimal therapy. The development of microsurgical techniques in the sixties contributed significantly to the progress in nerve repair. Since then, no major clinical innovation has become established. However, with an increased understanding of cellular and molecular mechanisms underlying nerve regeneration, various tubulization concepts have been developed which yield possible alternatives to direct suturing and to autologous nerve grafting in cases of short nerve defects. The vast knowledge gathered in the field of nerve regeneration needs to be further exploited in order to develop alternative therapeutic strategies to nerve autografting, which can result in donor-site defects and often lead to inappropriate results. Considering the encouraging results from preclinical studies, innovative nerve repair strategies are likely to improve the outcome of reconstructive surgical interventions. This paper outlines, in addition to the fundamentals of nerve regeneration, the current treatment options for defects of peripheral nerves. This article also reviews the developments in the use of alternative nerve guides and demonstrates new perspectives in the field of peripheral nerve reconstruction.


Asunto(s)
Procedimientos Neuroquirúrgicos/tendencias , Traumatismos de los Nervios Periféricos , Nervios Periféricos/cirugía , Animales , Trasplante de Células , Humanos , Tejido Nervioso/trasplante , Neuronas/trasplante , Nervios Periféricos/patología , Suturas , Cicatrización de Heridas/fisiología
10.
Acta Otolaryngol Suppl ; (556): 70-9, 2006 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17114147

RESUMEN

CONCLUSION: The results of this study are in accordance with the assumption that cognitive-oriented therapy enabling the patient to live with tinnitus is of primary importance to enhance quality of life. BACKGROUND AND OBJECTIVES: This study describes the success of an integrative behavioral-medicine inpatient treatment for complex chronic tinnitus and presents its long-term effects. In 1987 we developed and evaluated a new treatment concept of psychological treatment of complex chronic tinnitus based on international experience and results. To evaluate the influence, effects and individual results of the specific therapy we analyzed the data of 434 consecutively treated patients. To investigate the long-term effects of the treatment, we contacted the patients 15 years after discharge from the hospital. PATIENTS AND METHODS: We used the tinnitus questionnaire (TQ) and visual analog scales (VAS) for specific tinnitus variables (loudness, discomfort, control of tinnitus, stress, general mood). The German version of the Derogatis psychopathology checklist (SCL-90-R) was used to analyze the impact of additional symptoms (depression, anxiety, introversion, etc.). RESULTS: Compared with a control group (patients on a waiting list) significant and clinically relevant effects were found. At the outcome, there were significant improvements in almost all parameters measured. For evaluation of the long-term effect we succeeded in contacting 312 of 434 former patients. Data were assessed using the same questionnaires that had been employed at the first contact. In all, 271 patients (86%) returned the questionnaires. Data for 244 cases (mean age 63 years; 79 females, 165 males) were complete enough to be used for data analysis. The results of the follow-up were as unexpected as clear: 15 years after conclusion of the treatment, the improvements of the tinnitus parameters and additional symptoms were stable when compared with the end of therapy.


Asunto(s)
Terapia Conductista/métodos , Acúfeno/rehabilitación , Adaptación Psicológica , Adulto , Ansiedad/epidemiología , Enfermedad Crónica , Comorbilidad , Depresión/epidemiología , Femenino , Estudios de Seguimiento , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Trastornos de la Personalidad/epidemiología , Estudios Prospectivos , Encuestas y Cuestionarios , Factores de Tiempo , Acúfeno/epidemiología , Acúfeno/terapia , Resultado del Tratamiento
11.
MMW Fortschr Med ; 148(31-32): 31-3, 2006 Aug 03.
Artículo en Alemán | MEDLINE | ID: mdl-16937874

RESUMEN

CONTENT: Results of the German part of a European multicenter study on the effectiveness and practicability of an internet-based self-help program (SHG self-help guide) in bulimia nervosa (BN). METHOD: The internet-based program SHG builds on the principles of cognitive behavioral therapy (CBT) and comprises seven cumulative therapeutic steps. Twenty-two women with BN made use of the program over a period of six months. The patients were supported by three evaluation interviews and a once-weekly email contact with a female psychologist. During the interview, data on general psychopathology, specific eating disorder complaints and symptoms of depression were collected. RESULTS: The examination showed definite effects both in terms of a reduction in eating disorder-specific behavior and a statistically and clinically relevant improvement in the symptoms of depression. CONCLUSION: After working with the SHG, the patient sample studied here registered improvements in eating disorder and depressive symptoms. The design of the study, however, made it impossible to assess effectiveness. Practicability and usefulness were positively assessed by the patients. Thanks to its considerable flexibility in terms of time and place, the method could well be a valuable supplementary building block in the treatment of bulimia nervosa.


Asunto(s)
Bulimia/terapia , Terapia Cognitivo-Conductual , Internet , Derivación y Consulta , Grupos de Autoayuda , Adulto , Bulimia/psicología , Depresión/psicología , Depresión/terapia , Femenino , Estudios de Seguimiento , Humanos , Motivación , Proyectos Piloto
13.
Acta Psychiatr Scand Suppl ; (429): 36-40, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16445480

RESUMEN

OBJECTIVE: To describe the intervention effects of supplying homeless individuals with permanent housing. METHOD: In a prospective study, 109 male and 20 female homeless individuals were assessed at baseline and at 1- and 3-year follow-up concerning mental illness (SCID-I), psychopathology, global assessment of functioning, emotional lability and alcohol consumption. RESULTS: A high proportion (86%) of the individuals was able to maintain or improve stability of housing. Only minor changes were observed concerning mental illness and global functioning. Extensive alcohol consumption and high psychopathology increased the risk of losing the stable housing. CONCLUSION: The placement of homeless individuals in board and care homes or community housing after social counselling seems to be a necessary measure to remedy homelessness. However, supplying more permanent housing is not sufficient to decisively improve mental health status.


Asunto(s)
Vivienda , Personas con Mala Vivienda/psicología , Trastornos Psicóticos/rehabilitación , Esquizofrenia/rehabilitación , Actividades Cotidianas/clasificación , Actividades Cotidianas/psicología , Adulto , Síntomas Afectivos/epidemiología , Síntomas Afectivos/psicología , Síntomas Afectivos/rehabilitación , Alcoholismo/epidemiología , Alcoholismo/psicología , Alcoholismo/rehabilitación , Comorbilidad , Femenino , Estudios de Seguimiento , Alemania , Personas con Mala Vivienda/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Trastornos Psicóticos/epidemiología , Trastornos Psicóticos/psicología , Esquizofrenia/epidemiología , Psicología del Esquizofrénico , Resultado del Tratamiento
14.
J Orthop Res ; 24(1): 63-70, 2006 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-16419970

RESUMEN

Destruction of collagen within osteoarthritic cartilage depends in part on collagen-degrading matrix metalloproteases (MMP). Degradative fragments of type II collagen (Col II) occur in normal and in osteoarthritic cartilage, and may contribute to regulation of matrix turnover by interfering with normal cell-matrix communication pathways. Therefore, the effects of different types of collagen fragments on mRNA and protein levels of MMP-2, MMP-3, MMP-9, and MMP-13 in cultured bovine articular knee chondrocytes and explants were examined. Primary chondrocytes and explants were incubated with fragments from whole cartilage collagen matrix (Colf) and from purified type II collagen (Col2f), or with a synthetic 29-mer peptide representing the amino-terminal domain of type II collagen (Ntelo). Gelatin zymography revealed increases of proMMP-2, a shift towards active MMP-2 and increases in proMMP-9, depending on the type of fragment. In situ hybridization of cartilage sections displayed MMP-3 mRNA in virtually all cells. Moderate to strong increases in MMP-2, MMP-3, MMP-9, and MMP-13 mRNA levels were detected by quantitative PCR. The results demonstrate stimulating effects of collagen fragments on both mRNA and/or protein from MMP -2, -3, -9, and -13, and suggest a novel mechanism of MMP induction and activation that includes a particular role for N-telo in controlling catabolic pathways of matrix turnover.


Asunto(s)
Cartílago Articular/enzimología , Colágeno/metabolismo , Metaloproteinasas de la Matriz/biosíntesis , Secuencia de Aminoácidos , Animales , Cartílago Articular/efectos de los fármacos , Bovinos , Células Cultivadas , Condrocitos/efectos de los fármacos , Condrocitos/enzimología , Expresión Génica , Humanos , Hibridación Fluorescente in Situ , Metaloproteinasa 2 de la Matriz/biosíntesis , Metaloproteinasa 3 de la Matriz/biosíntesis , Metaloproteinasa 3 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/biosíntesis , Fragmentos de Péptidos/farmacología , ARN Mensajero/biosíntesis , Regulación hacia Arriba
15.
Nervenarzt ; 76(9): 1141-52; quiz 1153, 2005 Sep.
Artículo en Alemán | MEDLINE | ID: mdl-16133432

RESUMEN

Anorexic and bulimic eating disorders today are rather frequent in adolescent girls and young women of developed industrial countries. News media frequently report such patients, and lay people are interested. For scientists, it is not easy to explain the etiology and pathophysiology of these eating disorders. Clinically, treatment is a challenge. General risk factors for the development of anorexic and bulimic eating disorders are (1) female gender, (2) adolescence, and (3) living in an industrial country. Special risk factors are (1) obesity or mental disorders (eating, depression, substance use), (2) premorbid characteristics (early menarche, childhood obesity, anxiety disorder, low self-esteem, and perfectionism), and (3) premorbid stresses. Biological and sociocultural factors and personally threatening experiences all play a role in the etiology. Especially in early phases of the illness, affected patients do not appear to suffer, are reluctant to admit symptoms, and may avoid necessary treatment. Progress has recently been made in the understanding and treatment of anorexic and bulimic eating disorders.


Asunto(s)
Anorexia/diagnóstico , Anorexia/terapia , Bulimia/diagnóstico , Bulimia/terapia , Medición de Riesgo/métodos , Anorexia/epidemiología , Bulimia/epidemiología , Femenino , Humanos , Masculino , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina , Factores de Riesgo
16.
Psychoneuroendocrinology ; 30(6): 577-81, 2005 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-15808927

RESUMEN

The appetite-modulating hormone ghrelin transmits changes in food intake to the central nervous system. In patients with anorexia nervosa, weight gain reduces elevated fasting ghrelin levels to normal, however, less is known about the effects on postprandial ghrelin levels. In 20 female anorectic in-patients (25.6 +/- 1.0 years; body mass index (BMI) 15.1 +/- 0.3 kg/m2) a standardized test with 250 ml fluid meal (250 kcal: 9.4 g protein, 34.4 g carbohydrates, and 8.3 g fat) was performed at three different times (at admission, after partial weight gain of at least 2 kg, and at discharge) and compared to healthy controls (n = 6; BMI 21.1 +/- 0.7 kg/m2). Plasma ghrelin levels were measured preprandially as well as 20 and 60 min postprandially by a commercially available radioimmunoassay (Phoenix Pharmaceuticals, USA). At admission plasma ghrelin levels significantly decreased postprandially (from 871.9 +/- 124 to 620.3 +/- 80 pg/ml 60 min after meal; P < 0.005). After partial weight gain (2.8 +/- 0.1 kg; BMI 16.1 +/- 0.3 kg/m2) postprandial ghrelin concentrations decreased from 597.0 +/- 79 to 414.7 +/- 39 pg/ml (P < 0.0001), at discharge (weight gain: 7.6 +/- 0.5 kg; BMI 17.9 +/- 0.4 kg/m2) from 570.4 +/- 78 to 395.4 +/- 44 pg/ml (P < 0.0001). Mean postprandial ghrelin decrease was not significantly different between the three tests (29, 25, and 26%, respectively) or to controls (20%). In anorectic patients mean postprandial ghrelin decrease did not change during weight gain. These findings indicate that in anorexia nervosa the suppression of ghrelin release by acute changes of energy balance (feeding) is not disturbed and that it is independent from chronic changes in energy balance (weight gain).


Asunto(s)
Anorexia Nerviosa/sangre , Regulación del Apetito/fisiología , Ingestión de Alimentos/fisiología , Hormonas Peptídicas/sangre , Periodo Posprandial/fisiología , Aumento de Peso/fisiología , Adulto , Peso Corporal/fisiología , Metabolismo Energético/fisiología , Femenino , Ghrelina , Humanos , Valores de Referencia
17.
Fortschr Neurol Psychiatr ; 72(3): 136-46, 2004 Mar.
Artículo en Alemán | MEDLINE | ID: mdl-14999593

RESUMEN

Patients with somatoform disorders represent an expensive problem group of the healthcare system characterized by inappropriately high medical costs. This paper describes a controlled inpatient treatment study using a cognitive-behavioral approach. The aim of this treatment program was to improve the patients' symptomatology and their psychosocial functioning, as well as reducing unnecessary medical costs. We treated 172 patients with somatoform disorders (DSM-IV) and compared them with 262 patients of a waiting control list. An additional control group consisted of 123 patients with other mental disorders. Direct and indirect illness-related costs for the two-year periods before and after treatment were re-calculated using objective data provided by the health insurance companies. The results show a marked improvement in the areas of bodily complaints, health anxieties, dysfunctional beliefs towards body and health, depression and psychosocial impairments. The medical costs in the post-treatment period decreased by 1,098 euro (-36.7 %) for inpatient and 382 euro (-24.5 %) for outpatient treatments. Indirect costs due to days lost from work were 6,702 euro (-35.3 %) lower than during the two-years before treatment. The treatment costs had amortized after 21.5 months. We identified a subgroup of high-utilizing somatoform patients for which per patient savings of 32,174 euro (-63.9 %) were found. These results confirm that the cognitive-behavioral approach is effective in improving complaints as well as reducing the health-economical burden of somatoform disorders.


Asunto(s)
Trastornos Somatomorfos/economía , Trastornos Somatomorfos/terapia , Adulto , Análisis Costo-Beneficio , Femenino , Estudios de Seguimiento , Humanos , Pacientes Internos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Trastornos Somatomorfos/diagnóstico , Resultado del Tratamiento
18.
Eat Weight Disord ; 8(1): 26-35, 2003 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-12762622

RESUMEN

As part of a prospective, long-term treatment study, 30 in-patients with bulimia nervosa (BN) were divided into groups with high and low expressed emotion (EE) family backgrounds according to the Camberwell Family Interview, and followed for a period of six years. The high EE group initially showed significantly more psychopathology than the low EE group. No group x time interactions were found, but the high EE group showed a worse outcome on the "conflict" and "organisation" subscales of the Family Environment Scale. They also showed significantly more eating disorder pathology according to the Eating Disorder Inventory (EDI) and the Structured Interview for anorexia nervosa (AN) and BN before treatment at discharge, after two years and, to some degree, even after six years. Depth of depression (Beck Depression Inventory) was significantly higher in the high EE group at admission (moderate depression), discharge and after the 6-year follow-up (still slight depression). The Parental Bonding Instrument (PBI) showed no differences between the high EE and low EE groups, but the individuals with "affectionless control" according to the PBI had more negative scores on three of the subscales of the Family Environment Scale (FES). In brief, the high EE individuals with BN were initially sicker and did not fully catch up over time in comparison with the symptomatic recovery of the low EE individuals. These data suggest that EE status upon admission to in-patient treatment is a relevant predictor of the severity and course of BN and depressive symptoms.


Asunto(s)
Bulimia/psicología , Emoción Expresada , Apego a Objetos , Relaciones Padres-Hijo , Medio Social , Bulimia/diagnóstico , Trastorno Depresivo/psicología , Femenino , Alemania , Humanos , Masculino , Análisis Multivariante , Pronóstico , Estudios Prospectivos
19.
Mol Psychiatry ; 8(4): 397-406, 2003 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-12740597

RESUMEN

Serotonergic and opioidergic neurotransmitter system alterations have been observed in people with eating disorders; the genes for the serotonin 1D receptor (HTR1D) and the opioid delta receptor (OPRD1) are found on chr1p36.3-34.3, a region identified by our group in a linkage analysis of anorexia nervosa (AN). These candidate genes were evaluated for sequence variation and for linkage and association of this sequence variation to AN in family and case : control data sets. Resequencing of the HTR1D locus and a portion of the OPRD1 locus identified novel SNPs and confirmed existing SNPs. Genotype assay development and genotyping of nine SNPs (four at HTR1D and five at OPRD1) was performed on 191 unrelated individuals fulfilling DSM-IV criteria (w/o amenorrhea criterion) for AN, 442 relatives of AN probands and 98 psychiatrically screened controls. Linkage analysis of these candidate gene SNPs with 33 microsatellite markers in families including relative pairs concordantly affected with restricting AN (N=37) substantially increased the evidence for linkage of this region to restricting AN to an NPL score of 3.91. Statistically significant genotypic, allelic, and haplotypic association to AN in the case : control design was observed at HTR1D and OPRD1 with effect sizes for individual SNPs of 2.63 (95% CI=1.21-5.75) for HTR1D and 1.61 (95% CI=1.11-2.44) for OPRD1. Using genotype data on parents and AN probands, three SNPs at HTR1D were found to exhibit significant transmission disequilibrium (P&<0.05). The combined statistical genetic evidence suggests that HTR1D and OPRD1 or linked genes may be involved in the etiology of AN.


Asunto(s)
Anorexia Nerviosa/genética , Cromosomas Humanos Par 1 , Polimorfismo de Nucleótido Simple , Receptor de Serotonina 5-HT1D/genética , Receptores Opioides delta/genética , Mapeo Cromosómico , Femenino , Frecuencia de los Genes , Variación Genética , Genotipo , Haplotipos , Humanos , Masculino , Valores de Referencia
20.
Behav Res Ther ; 40(11): 1275-89, 2002 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-12384323

RESUMEN

OBJECTIVE: This study examined outcome differences of 109 obese subjects, who participated in a 10-week cognitive-behavioral inpatient treatment followed by either a weight maintenance program or a follow-up period without professional support. METHODS: Self-rated weight loss, eating behaviors, and general psychopathology were assessed several months before treatment, when subjects were admitted, at discharge, and at the 6-, 12-, and 18-month follow-ups. Structured interviews for mental disorders and eating pathology were conducted additionally. RESULTS: The mean weight of the sample at baseline was 127 kg. Weight loss of the total sample amounted to 8.0 kg (6.3%) and was completely maintained during the follow-up period. Significant reductions of eating and general psychopathology were observed at the 18-month follow-up. The outcome in the maintenance condition did not significantly differ from the outcome in the control condition. CONCLUSIONS: Weight regain after obesity treatment is not inevitable, but continuous patient-therapist contacts do not distinctly improve treatment effects.


Asunto(s)
Terapia Cognitivo-Conductual/métodos , Obesidad/terapia , Pérdida de Peso , Adulto , Índice de Masa Corporal , Ingestión de Energía , Femenino , Estudios de Seguimiento , Humanos , Trastornos Mentales/diagnóstico , Trastornos Mentales/epidemiología , Trastornos Mentales/etiología , Obesidad/psicología , Escalas de Valoración Psiquiátrica , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Factores de Tiempo
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