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Voice power is an important concept in daily life of voice hearers and in the support and therapy for voice hearers who seek help. Therefore, the ability to examine voice power differentials between a voice and a voice hearer is essential. The present study aimed to collect data on voice power differentials and to further validate the Voice Power Differential Scale (VPD). 105 participants aged ≥ 18 with an ICD10 F2-diagnosis that included hearing voices were included in this study. Internal consistency was good (alpha = 0.792), as well as test-retest-reliability (r = 0.855) and correlations with other constructs were generally as expected. The VPD questionnaire results correlated negatively with the Beliefs About Voices Questionnaire-Revised's (BAVQ-R) items of Benevolence and Engagement-emotion. It correlated positively with Omnipotence and Resistance-emotion, as well as with Negative Content on the Psychotic Symptoms Rating-Scale (PSYRATS). Unexpectedly, no correlations were found with overall severity and command hallucinations. The Voice Power Differential Scale is an important tool for assessing and formulating a voice hearer's experience when they seek treatment or support for their verbal auditory hallucinations. The results of this study enrich the on-going discussion about the importance of voice power for voice hearers.
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Alucinaciones/diagnóstico , Lenguaje , Escalas de Valoración Psiquiátrica , Voz , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
AIMS: The way an individual handles the experience of psychosis, the so-called 'recovery style', has been shown to substantially affect long-term outcomes. The Recovery Style Questionnaire (RSQ) measures this psychological dimension. The aim of this study was to provide a validation of the German version of the RSQ and to raise awareness for recovery-oriented approaches. METHODS: The RSQ was translated into German according to the guidelines of the WHO and patients were administered this questionnaire and measures of internalised stigma, psychotic symptoms, illness concept, empowerment, self-esteem and quality of life. Descriptive statistics were demonstrated to characterise the sample. Reliability was assessed in different forms: internal consistency, test-retest reliability and split-half reliability. Items were evaluated with descriptive data and item-total correlations. Convergent and discriminant validity were shown, and a confirmatory factor analysis was performed. In order to ameliorate the model, a post hoc model modification was done. RESULTS: The sample consisted of 138 patients diagnosed with schizophrenia spectrum disorders (mean age: 35.7 years; 53.6% men; mean duration of illness: 20.6 years) with a mean RSQ overall percentage of 66.12 (s.d. ± 17.43%), mainly representing the categories 'mixed picture' and 'tends towards integration'. The reliability of the RSQ was acceptable with a Cronbach's α of 0.741 and a test-retest coefficient of 0.502. Item-total correlations were not acceptable for 27 of 39 items. Moderate evidence for convergent validity of the RSQ was found. Confirmatory factor analysis revealed that the 13-factor model with 39 items originally proposed was partially poorly replicated in the present sample (χ2 ratio to degrees of freedom (χ2/df) of 1.732, Comparative Fit Index (CFI) of 0.585, Normed Fit Index (NFI) of 0.414, Tucker-Lewis Index (TLI) of 0.508, root mean square error of approximation (RMSEA) of 0.095). The RSQ was modified based on item-total correlations and path coefficients of the single items. The confirmatory factor analysis of the resulting one-factor model with 11 items showed adequate fit to the data (χ2/df of 1.562, CFI of 0.936, NFI of 0.847, TLI of 0.910, RMSEA of 0.083) and demonstrated good model fit. CONCLUSIONS: Despite partially insufficient psychometric data of the original RSQ, the concept of recovery style is beneficial to psychiatric research and clinical practice. The underlying idea is valuable, and the questionnaire needs further development. Therefore, a short version of the RSQ is proposed.
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Adaptación Psicológica , Recuperación de la Salud Mental , Trastornos Psicóticos/psicología , Estigma Social , Encuestas y Cuestionarios/normas , Adolescente , Adulto , Anciano , Análisis Factorial , Alemania , Humanos , Persona de Mediana Edad , Psicometría , Trastornos Psicóticos/rehabilitación , Reproducibilidad de los Resultados , Traducción , Adulto JovenRESUMEN
BACKGROUND: Within academic psychiatry, women are underrepresented in the higher academic ranks. However, basic determinants of women's lack of academic advancement such as publication activity are poorly understood. The present study examines women's publication activity in high-impact psychiatry journals over two decades and reports developments in the numbers of male and female authorship over time and across cultural areas. METHODS: We conducted a retrospective bibliometric review of all articles published in 2004 and 2014 in three high-ranking general psychiatry journals. Statistical comparisons were made between the two years and with results from a baseline assessment in 1994. RESULTS: The overall percentage of female authors increased from 24.6% in 1994 to 33.2% in 2004 to 38.9% in 2014. Though increases in female authorship were statistically significant for both decades, there was less difference between 2004 and 2014, indicating a possible ceiling effect. Rates of female first authors increased between 1994 and 2014, though to a lesser degree between 2004 and 2014. Numbers of female corresponding authors plateaued between 2004 and 2014. Within Europe, Scandinavia displayed the most balanced gender-wise first author ratios. Western European and Central European countries increased their rates of female first authors substantially between 2004 and 2014. CONCLUSIONS: Despite gains in some areas, our study reveals considerable deficits in the diversity of the current academic psychiatric landscape. Ongoing efforts and interventions to enhance the participation of underrepresented groups on institutional, political and editorial levels are necessary to diversify psychiatric research.
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Autoria , Publicaciones Periódicas como Asunto , Psiquiatría/tendencias , Mujeres Trabajadoras/estadística & datos numéricos , Bibliometría , Europa (Continente) , Femenino , Humanos , Masculino , Estudios Retrospectivos , Factores Sexuales , Encuestas y CuestionariosRESUMEN
OBJECTIVE: Home care of advanced cancer patients often has adverse effects on physical and mental health of family caregivers. Little is known about the long-term effects of continuous caregiving on mental health as compared with the effects of bereavement. The objectives of this study were to describe the course of psychiatric morbidity in family caregivers over time, to identify the impact of the patients' death on caregivers, and to explore possible predictor variables for psychiatric morbidity. METHODS: This multi-institutional, prospective study included 80 family caregivers of 80 advanced cancer patients for baseline and 9 months follow-up assessment. Possible psychiatric disorders (ie, depression, anxiety, posttraumatic stress disorder, and alcohol abuse/dependence) as well as potentially predictive factors (ie, sociodemographic factors, burden, hope, and coping mechanisms) were assessed. RESULTS: Follow-up assessment was conducted on average 9.2 months (±2.9) after baseline assessment. Prevalence rates of anxiety and posttraumatic stress disorder decreased significantly over time, whereas depression and alcoholism remained stable. Bereavement was experienced by 53% of caregivers in the follow-up period. The patients' death had no influence on psychiatric morbidity at follow-up. Predictors for the development of a psychiatric disorder varied according to condition, with hope and emotion-oriented coping identified as important influences, especially for anxiety and depression. CONCLUSION: Family caregivers with certain psychiatric disorders might need targeted psychosocial support to ensure their mental well-being and prevent long-term disability. Supporting hope and functional coping strategies early after the patient's diagnosis might limit development and extent of psychiatric morbidity.
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Aflicción , Cuidadores/psicología , Esperanza , Neoplasias/psicología , Adaptación Psicológica , Adulto , Anciano , Depresión/psicología , Femenino , Humanos , Masculino , Salud Mental , Persona de Mediana Edad , Estudios Prospectivos , Trastornos por Estrés Postraumático/psicologíaRESUMEN
PURPOSE: Informal caregivers of advanced cancer patients are known to suffer from high distress due to their caregiving responsibilities. Nevertheless, a comprehensive evaluation of psychiatric morbidity is often missing in clinical practice due to time resources, and mental health problems may be unnoticed in this population. A feasible approach is needed to identify caregivers at risk for psychiatric disorders to offer targeted interventions and enhance their well-being. METHODS: This cross-sectional, multi-institutional study screened 345 caregivers of advanced cancer patients for psychiatric disorders (i.e., depression, anxiety, posttraumatic stress disorder, and alcohol abuse/dependence) and assessed factors potentially associated with mental health diagnoses (including socio-demographic factors, burden, hope, caring-related quality of life, and coping preferences). RESULTS: Overall, almost 52 % of participants had one or more suspected psychiatric disorders, with anxiety being the most prevalent. Perceived hope, higher burden, and more emotion-oriented coping were associated with psychiatric morbidity in this sample. Spouses and parents showed significantly more symptoms of psychiatric disorders than other relatives. CONCLUSIONS: This study confirms the high risk of informal caregivers of advanced cancer patients to develop psychiatric disorders and suggests a practically feasible approach to identify at risk caregivers to offer support.
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Cuidadores/psicología , Costo de Enfermedad , Trastornos del Humor , Neoplasias , Cuidados Paliativos/psicología , Calidad de Vida , Trastornos por Estrés Postraumático , Estrés Psicológico/prevención & control , Adaptación Psicológica , Adulto , Anciano , Australia , Estudios Transversales , Femenino , Humanos , Masculino , Salud Mental , Persona de Mediana Edad , Trastornos del Humor/diagnóstico , Trastornos del Humor/etiología , Trastornos del Humor/prevención & control , Neoplasias/psicología , Neoplasias/terapia , Prevalencia , Trastornos por Estrés Postraumático/diagnóstico , Trastornos por Estrés Postraumático/etiología , Trastornos por Estrés Postraumático/prevención & controlRESUMEN
The comprehensive assessment of symptoms is the basis for effective, individualised palliative treatment. Established scoring systems provide in-depth information but are often lengthy and hence unsuitable. We introduce the PERS(2) ON score as a short and practically feasible score to evaluate symptom burden. Fifty patients admitted to a Palliative Care Unit rated seven items, i.e. pain, eating (loss of appetite/weight loss), rehabilitation (physical impairment), social situation (possibility for home care), suffering (anxiety/burden of disease/depression), O2 (dyspnoea) and nausea/emesis, on a scale ranging from 0 (absence) to 10 (worst imaginable), resulting in a score ranging from 0 to 70. Assessments were performed at admission, 7 days after admission and at the day of discharge. Symptom intensity scores were calculated, and change over time was evaluated. A significant improvement was observed from the PERS²ON score between admission and 7 days (P < 0.001; paired t-test). Significant improvement from baseline evaluation to evaluation on the day of discharge was observed (P = 0.001; paired t-test). This study provides initial evidence that the PERS²ON score is both feasible and sensitive to changes of the most prominent symptoms in palliative care. It may be useful in clinical practice to direct palliative treatment strategies and provide targeted symptom management.
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Neoplasias/psicología , Cuidados Paliativos/psicología , Adulto , Anciano , Anciano de 80 o más Años , Ansiedad/psicología , Actitud Frente a la Salud , Disnea/psicología , Estudios de Factibilidad , Femenino , Servicios de Atención de Salud a Domicilio , Humanos , Estado de Ejecución de Karnofsky , Masculino , Persona de Mediana Edad , Náusea/psicología , Dolor/psicología , Comodidad del Paciente , Proyectos Piloto , Estudios Prospectivos , Calidad de Vida , Encuestas y Cuestionarios , Vómitos/psicologíaRESUMEN
This paper reviews the literature on positive psychology with a special focus on people with mental illness. It describes the characteristics, critiques, and roots of positive psychology and positive psychotherapy, and summarises the existing evidence on positive psychotherapy. Positive psychology aims to refocus psychological research and practice on the positive aspects of experience, strengths, and resources. Despite a number of conceptual and applied research challenges, the field has rapidly developed since its introduction at the turn of the century. Today positive psychology serves as an umbrella term to accommodate research investigating positive emotions and other positive aspects such as creativity, optimism, resilience, empathy, compassion, humour, and life satisfaction. Positive psychotherapy is a therapeutic intervention that evolved from this research. It shows promising results for reducing depression and increasing well-being in healthy people and those with depression. Positive psychology and positive psychotherapy are increasingly being applied in mental health settings, but research evidence involving people with severe mental illness is still scarce. The focus on strengths and resources in positive psychology and positive psychotherapy may be a promising way to support recovery in people with mental illness, such as depression, substance abuse disorders, and psychosis. More research is needed to adapt and establish these approaches and provide an evidence base for their application.
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Trastornos Mentales/terapia , Psicoterapia/métodos , Humanos , Servicios de Salud Mental , Resultado del TratamientoRESUMEN
Background. Well-being is important for people with severe mental illness, such as psychosis. So far, no clear concept of well-being exists for this client group. A recent systematic review and narrative synthesis developed a static framework of well-being components. The present study aims to validate the static framework and to illuminate the processes by which well-being is experienced by people with psychosis. Methods. Semi-structured interviews were conducted with 23 service users with psychosis exploring their experience of well-being. Thematic analysis was used to analyse the data employing techniques taken from grounded theory to enhance the rigour of the analysis. Respondent validation was undertaken with 13 of the 23 participants. Results. Three superordinate categories of well-being were identified: current sense of self; transition to enhanced sense of self and enhanced sense of self. In the dynamic process of improving well-being the current sense of self undergoes a transition to an enhanced sense of self. The four factors influencing the transition are consistent with the static framework of well-being, hence validating the static framework. In addition, we identified three determinants of current sense of self and seven indicators of enhanced sense of self, which represent the achievement of improved well-being. Conclusions. This study provides an empirically defensible framework for understanding well-being in terms of determinants, influences and indicators. The influences are targets for interventions to improve well-being, and the indicators are outcome domains to assess the effectiveness of services in supporting well-being.
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Aims. Insight, positive and negative symptoms, hope, depression and self-stigma are relevant variables in schizophrenia spectrum disorders. So far, research on their mutual influences has been patchy. This study simultaneously tests the associations between these variables. Methods. A total of 284 people with schizophrenia spectrum disorders were assessed using the Schedule for the Assessment of Insight, Positive and Negative Syndrome Scale, Integrative Hope Scale, Centre for Epidemiological Studies Depression Scale and Internalized Stigma of Mental Illness scale. Path analysis was applied to test the hypothesized relationships between the variables. Results. Model support was excellent. Strong and mutual causal influences were confirmed between hope, depression and self-stigma. The model supported the assumption that insight diminishes hope and increases depression and self-stigma. While negative symptoms directly affected these three variables, reducing hope and increasing depression and self-stigma, positive symptoms did not. However, positive symptoms diminished self-stigma on a pathway via insight. Conclusions. This study provides a comprehensive synopsis of the relationships between six variables relevant for schizophrenia spectrum disorders. Research implications include the need to investigate determinants of consequences of insight, and the sequence of influences exerted by positive and negative symptoms. Clinical implications include the importance of interventions against self-stigma and of taking a contextualized approach to insight.
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As Pompe disease glycogen storage disease type 2 with a severely reduced life expectancy is now a treatable disorder, accurate diagnostic procedures and evidence-based indications for therapy are mandatory. We screened the literature for consensus reports and published trial data of late-onset Pompe disease. These data were summarized in a Delphi consensus method approach. The clinical suspicion of late-onset Pompe disease should be substantiated by the validated dry blood spot test measurement for acid α-glucosidase activity. Alternatively, enzyme activity analysis in lymphocytes is also feasible. Glucosidase α gene sequencing for verifying the diagnosis is recommended. A muscle biopsy including measurements of acid α-glucosidase activity and glycogen concentration is warranted for differential diagnosis in selected cases. The confirmed diagnosis should lead to a multidisciplinary treatment approach, possibly including enzyme replacement therapy.
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Enfermedad del Almacenamiento de Glucógeno Tipo II/diagnóstico , Enfermedad del Almacenamiento de Glucógeno Tipo II/tratamiento farmacológico , Adulto , Factores de Edad , Biopsia , Conducta Cooperativa , Estudios Transversales , Técnica Delphi , Diagnóstico Diferencial , Enfermedad del Almacenamiento de Glucógeno Tipo II/epidemiología , Adhesión a Directriz , Humanos , Comunicación Interdisciplinaria , Imagen por Resonancia Magnética , Músculo Esquelético/patología , Examen Neurológico , Ensayos Clínicos Controlados Aleatorios como Asunto , alfa-Glucosidasas/uso terapéuticoRESUMEN
OBJECTIVE: The quality of life (QOL) of patients with schizophrenia has been found to be positively correlated with the social network and empowerment, and negatively correlated with stigma and depression. However, little is known about the way these variables impact on the QOL. The study aims to test the hypothesis that the social network, stigma and empowerment directly and indirectly by contributing to depression influence the QOL in patients with schizophrenia and schizoaffective disorders. METHOD: Data were collected on demographic and clinical variables, internalized stigma, perceived devaluation and discrimination, empowerment, control convictions, depression and QOL. Structural equation modelling (SEM) was applied to examine the impact of the above-mentioned constructs on QOL. RESULTS: The influences of the social network, stigma, empowerment and depression on QOL were supported by the SEM. A poor social network contributed to a lack of empowerment and stigma, which resulted in depression and, in turn, in poor QOL. Interestingly, however, the social network and stigma did not show a direct effect on QOL. CONCLUSION: Following a recovery approach in mental health services by focusing on the improvement of the social network, stigma reduction and especially on the development of personal strength has the potential to reduce depression in patients with psychosis and improving their QOL.
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Poder Psicológico , Calidad de Vida/psicología , Psicología del Esquizofrénico , Apoyo Social , Estereotipo , Adulto , Depresión/psicología , Femenino , Humanos , Masculino , Escalas de Valoración Psiquiátrica , Trastornos Psicóticos/psicología , Encuestas y CuestionariosRESUMEN
A 47-year-old patient with a history of Guillain-Barré syndrome three years prior to evaluation and a severe persisting sensory neuronopathy, complained of dysphagia especially for solid food. He also had severe, intermittent retrosternal pain. Radiological and manometric studies showed the typical features of achalasia. Treatment with botulinum toxin injection improved the dysphagia but not the retrosternal pain. An autoimmune response triggered by an infection is discussed as one possible cause of ganglion cell degeneration within the myenteric plexus in patients with achalasia. Such a hypothesis is supported by our observation showing the simultaneous occurrence of achalasia, sensory neuronopathy, and Guillain-Barré syndrome.
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Trastornos de Deglución/etiología , Acalasia del Esófago/diagnóstico , Síndrome de Guillain-Barré/diagnóstico , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/inmunología , Toxinas Botulínicas Tipo A/uso terapéutico , Dolor en el Pecho/etiología , Trastornos de Deglución/tratamiento farmacológico , Trastornos de Deglución/inmunología , Acalasia del Esófago/tratamiento farmacológico , Acalasia del Esófago/inmunología , Esofagoscopía , Síndrome de Guillain-Barré/tratamiento farmacológico , Síndrome de Guillain-Barré/inmunología , Humanos , Masculino , Manometría , Persona de Mediana Edad , Plexo Mientérico/inmunología , Degeneración Nerviosa/diagnóstico , Degeneración Nerviosa/inmunología , Examen NeurológicoRESUMEN
OBJECTIVE: Hope has long been considered an important therapeutic factor in medicine, nursing and mental health and recently received attention as a central component of recovery. However, conceptual clarity, applicability and the predictive value of hope remain unclear. This review aims to define hope, review current approaches to assessment, and outline research evidence linking hope with effectiveness. METHOD: We conducted a comprehensive review of publications on the conceptualisation and measurement of hope, and on its use as a predictive variable specifically in mental health patients. RESULTS: Forty-nine definitions of hope were identified, which were grouped into seven emergent dimensions. Thirty-two measurement tools were identified, although few have been used in research involving mental health patients. Eleven studies investigated hope as a predictive variable for differing outcomes, with inconclusive results. CONCLUSION: Many conceptual frameworks for hope have been proposed, but empirical evidence on its predictive power in mental health is lacking.
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Trastornos Mentales/terapia , Servicios de Salud Mental , Motivación , Psiquiatría , Trastornos de Ansiedad/psicología , Trastornos de Ansiedad/terapia , Trastorno Depresivo Mayor/psicología , Trastorno Depresivo Mayor/terapia , Objetivos , Humanos , Individualidad , Intención , Control Interno-Externo , Relaciones Interpersonales , Trastornos Mentales/psicología , Inventario de Personalidad , Psicoterapia/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Prueba de RealidadRESUMEN
Spinal muscular atrophy (SMA) is a recessive neuromuscular disorder caused by loss of the SMN1 gene. The clinical distinction between SMA type I to IV reflects different age of onset and disease severity. SMN2, a nearly identical copy gene of SMN1, produces only 10% of full-length SMN RNA/protein and is an excellent target for a potential therapy. Several clinical trials with drugs that increase the SMN2 expression such as valproic acid and phenylbutyrate are in progress. Solid natural history data for SMA are crucial to enable a correlation between genotype and phenotype as well as the outcome of therapy. We provide genotypic and phenotypic data from 115 SMA patients with type IIIa (age of onset <3 years), type IIIb (age of onset >3 years) and rare type IV (onset >30 years). While 62% of type IIIa patients carry two or three SMN2 copies, 65% of type IIIb patients carry four or five SMN2 copies. Three type IV SMA patients had four and one had six SMN2 copies. Our data support the disease-modifying role of SMN2 leading to later onset and a better prognosis. A statistically significant correlation for > or =4 SMN2 copies with SMA type IIIb or a milder phenotype suggests that SMN2 copy number can be used as a clinical prognostic indicator in SMA patients. The additional case of a foetus with homozygous SMN1 deletion and postnatal measurement of five SMN2 copies illustrates the role of genotypic information in making informed decisions on the management and therapy of such patients.
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Proteína de Unión a Elemento de Respuesta al AMP Cíclico/genética , Dosificación de Gen , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/prevención & control , Proteínas del Tejido Nervioso/genética , Proteínas de Unión al ARN/genética , Adulto , Edad de Inicio , Femenino , Eliminación de Gen , Homocigoto , Humanos , Masculino , Linaje , Fenotipo , Proteínas del Complejo SMN , Proteína 1 para la Supervivencia de la Neurona Motora , Proteína 2 para la Supervivencia de la Neurona MotoraRESUMEN
UNLABELLED: Increasing evidence has suggested that oxidative stress may be involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). The antioxidant vitamin E (alpha-tocopherol) has been shown to slow down the onset and progression of the paralysis in transgenic mice expressing a mutation in the superoxide dismutase gene found in certain forms of familial ALS. The current study, a double blind, placebo-controlled, randomised, stratified, parallel-group clinical trial, was designed to determine whether vitamin E (5000 mg per day) may be efficacious in slowing down disease progression when added to riluzole. METHODS: 160 patients in 6 German centres with either probable or definite ALS (according to the El Escorial Criteria) and a disease duration of less than 5 years, treated with riluzole, were included in this study and were randomly assigned to receive either alpha-tocopherol (5000 mg per day) or placebo for 18 months. The Primary outcome measure was survival, calculating time to death, tracheostomy or permanent assisted ventilation, according to the WFN-Criteria of clinical trials. Secondary outcome measures were the rate of deterioration of function assessed by the modified Norris limb and bulbar scales, manual muscle testing (BMRC), spasticity scale, ventilatory function and the Sickness Impact Profile (SIP ALS/19). Patients were assessed at entry and every 4 months thereafter during the study period until month 16 and at a final visit at month 18. Vitamin E samples were taken for compliance check and Quality Control of the trial. For Safety, a physical examination was performed at baseline and then every visit until the treatment discontinuation at month 18. Height and weight were recorded at baseline and weight alone at the follow-up visits. A neurological examination as well as vital signs (heart rate and blood pressure), an ECG and VEP's were recorded at each visit. Furthermore, spontaneously reported adverse experiences and serious adverse events were documented and standard laboratory tests including liver function tests performed. For Statistical Analysis, the population to be considered for the primary outcome measure was an "intent-to-treat" (ITT) population which included all randomised patients who had received at least one treatment dose (n = 160 patients). For the secondary outcome measures, a two way analysis of variance was performed on a patient population that included all randomised patients who had at least one assessment after inclusion. RESULTS: Concerning the primary endpoint, no significant difference between placebo and treatment group could be detected either with the stratified Logrank or the Wilcoxon test. The functional assessments showed a marginal trend in favour of vitamin E, without reaching significance. CONCLUSION: Neither the primary nor the secondary outcome measures could determine whether a megadose of vitamin E is efficacious in slowing disease progression in ALS as an add-on therapy to riluzol. Larger or longer studies might be needed. However, administration of this megadose does not seem to have any significant side effects in this patient population.
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Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Riluzol/uso terapéutico , Vitamina E/administración & dosificación , Vitaminas/administración & dosificación , Esclerosis Amiotrófica Lateral/mortalidad , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Vitamina E/efectos adversos , Vitamina E/sangre , Vitaminas/efectos adversos , Vitaminas/sangreRESUMEN
Recently, a congenital myasthenic syndrome (CMS) with end-plate acetylcholine receptor (AChR) deficiency due to missense mutations in the genes for the AChR subunit was described. The first observed patient with this CMS was heteroallelic for the two epsilon-AChR subunit mutations epsilon1101insT and epsilon1293insG. This patient had only a moderate phenotype with mild muscle weakness and abnormal fatigue. We have now found homozygosity for the epsilon1293insG mutation in a severely affected CMS patient, who lost the ability to walk in midchildhood and shows profound weakness and muscle wasting. Our observation allows a genotype-phenotype correlation illustrating how differences in the AChR mutation haplotype can profoundly influence disease severity.
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Homocigoto , Mutación/genética , Síndromes Miasténicos Congénitos/genética , Receptores Colinérgicos/genética , Adulto , Femenino , Haplotipos/genética , Humanos , Músculos/patología , Síndromes Miasténicos Congénitos/patología , LinajeRESUMEN
Childhood spinal muscular atrophy (SMA) is a common autosomal recessive disorder which is characterized by muscle weakness due to degeneration of motoneurons in the spinal cord and brainstem nuclei. Positional cloning strategies have revealed several gene candidates including the genes for the survival motoneuron (SMN) and the neuronal apoptosis inhibitory protein (NAIP). Both genes are duplicated on chromosome 5. Homozygous deletions/mutations of the telomeric SMN gene, which is expressed from both copies on human chromosome 5, are associated with the disease. Recent reports suggest involvement of the SMN protein in the formation of spliceosomal particles in the cytoplasm and in the regeneration of spliceosomes in the nucleus. These data put spinal muscular atrophy into a growing group of disorders of RNA metabolism which also include fragile-X syndrome and myotonic dystrophy. Relevance of these previous data for the pathogenesis of the disease are discussed in this review.
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Cromosomas Humanos Par 5/genética , Neuronas Motoras/patología , Proteínas del Tejido Nervioso/genética , Atrofias Musculares Espinales de la Infancia/genética , Animales , Apoptosis/genética , Supervivencia Celular , Niño , Proteína de Unión a Elemento de Respuesta al AMP Cíclico , Modelos Animales de Enfermedad , Humanos , Ratones , Ratones Noqueados , Mutación Puntual , Proteínas de Unión al ARN , Proteínas del Complejo SMN , Atrofias Musculares Espinales de la Infancia/fisiopatologíaRESUMEN
Proximal spinal muscular atrophy (SMA) is a common motor neuron disease in humans and in its most severe form causes death by the age of 2 years. It is caused by defects in the telomeric survival motor neuron gene ( SMN1 ), but patients retain at least one copy of a highly homologous gene, centromeric SMN ( SMN2 ). Mice possess only one survival motor neuron gene ( Smn ) whose loss is embryonic lethal. Therefore, to obtain a mouse model of SMA we created transgenic mice that express human SMN2 and mated these onto the null Smn (-/-)background. We show that Smn (-/-); SMN2 mice carrying one or two copies of the transgene have normal numbers of motor neurons at birth, but vastly reduced numbers by postnatal day 5, and subsequently die. This closely resembles a severe type I SMA phenotype in humans and is the first report of an animal model of the disease. Eight copies of the transgene rescues this phenotype in the mice indicating that phenotypic severity can be modulated by SMN2 copy number. These results show that SMA is caused by insufficient SMN production by the SMN2 gene and that increased expression of the SMN2 gene may provide a strategy for treating SMA patients.
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Atrofia Muscular Espinal/genética , Proteínas del Tejido Nervioso/genética , Animales , Animales Recién Nacidos , Northern Blotting , Western Blotting , Tronco Encefálico/metabolismo , Tronco Encefálico/patología , Centrómero , Proteína de Unión a Elemento de Respuesta al AMP Cíclico , Modelos Animales de Enfermedad , Exones , Dosificación de Gen , Genotipo , Humanos , Técnicas In Vitro , Ratones , Ratones Transgénicos , Microinyecciones , Neuronas Motoras/patología , Atrofia Muscular Espinal/mortalidad , Atrofia Muscular Espinal/patología , Proteínas del Tejido Nervioso/metabolismo , Proteínas de Unión al ARN , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteínas del Complejo SMN , Médula Espinal/metabolismo , Médula Espinal/patología , Proteína 1 para la Supervivencia de la Neurona Motora , Proteína 2 para la Supervivencia de la Neurona MotoraRESUMEN
Spinal muscular atrophy (SMA) is caused by deletion or specific mutations of the telomeric survival motor neuron ( SMN ) gene on human chromosome 5. The human SMN gene, in contrast to the Smn gene in mouse, is duplicated and the centromeric copy on chromosome 5 codes for transcripts which preferentially lead to C-terminally truncated SMN protein. Here we show that a 46% reduction of Smn protein levels in the spinal cord of Smn heterozygous mice leads to a marked loss of the cytoplasmic Smn pool and motor neuron degeneration resembling spinal muscular atrophy type 3. Smn heterozygous mice described here thus represent a model for the human disease. These mice could allow screening for SMA therapies and help in gaining further understanding of the pathophysiological events leading to motor neuron degeneration in SMA.
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Proteínas del Tejido Nervioso/genética , Atrofias Musculares Espinales de la Infancia/genética , Animales , Animales Recién Nacidos , Western Blotting , Proteína de Unión a Elemento de Respuesta al AMP Cíclico , Modelos Animales de Enfermedad , Dosificación de Gen , Humanos , Inmunohistoquímica , Ratones , Ratones Endogámicos C57BL , Neuronas Motoras/metabolismo , Neuronas Motoras/patología , Proteínas del Tejido Nervioso/metabolismo , Nervio Frénico/patología , Empalme del ARN , ARN Mensajero/análisis , Proteínas de Unión al ARN , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteínas del Complejo SMN , Nervio Ciático/patología , Médula Espinal/metabolismo , Atrofias Musculares Espinales de la Infancia/metabolismo , Atrofias Musculares Espinales de la Infancia/patologíaRESUMEN
Botulin toxin (BoTx) injections are an alternative treatment for uncomplicated anal fissures. Until recently, surgical management has been advocated for therapeutic failure of BoTx and recurrent fissures. In 20 patients with recurring anal fissure we examined the remission rate following a second course of botulin treatment. The dose was identical to the first treatment (5 units Botox). In group 2, 30 patients with therapeutic failure were treated with a higher dose of botulin toxin (10 units). In our patients with recurring fissure, 19 of 20 were pain-free within a week (95%). After three months, 14 patients (70%) had healed fissures. In group 2, 22 of 30 patients (73%) became pain-free within the first week following the second course of treatment. Two patients (7%) suffered from transient mild incontinence. Nineteen patients (63%) showed healed fissures three months following the second BoTx treatment. BoTx remains an effective treatment in recurring anal fissure as well as in patients with therapeutic failure of prior BoTx injections.