RESUMEN
OBJECTIVE: To report that antibodies to synaptic proteins may occur in association with slow, progressive cognitive decline. METHODS: A total of 24 patients with progressive cognitive dysfunction of unclear etiology were examined for onconeuronal and synaptic receptor antibodies. The effect of serum was examined in cultures of dissociated mouse hippocampal neurons. RESULTS: Seven patients had immunoglobulin A (IgA), but no immunoglobulin G (IgG), antibodies against NMDA receptor (NMDAR). Anti-NMDAR IgA positive patients' serum, but not serum from control individuals, caused dramatic decrease of the levels of NMDAR and other synaptic proteins in neurons, along with prominent changes in NMDAR-mediated currents. These effects correlated with the titer of IgA NMDAR antibodies and were reversed after removing patients' serum from the culture media. When available, comprehensive clinical assessment and brain metabolic imaging showed neurologic improvement after immunotherapy. CONCLUSIONS: A subset of patients with slowly progressive cognitive impairment has an underlying synaptic autoimmunity that decreases the density of NMDAR and other synaptic proteins, and alters synaptic currents. This autoimmunity can be demonstrated examining patients' serum and CSF for NMDAR IgA antibodies, identifying possible candidates for immunotherapy.
Asunto(s)
Trastornos del Conocimiento/inmunología , Inmunoglobulina A/sangre , Inmunoglobulina A/inmunología , Intercambio Plasmático , Receptores de N-Metil-D-Aspartato/inmunología , Sinapsis/inmunología , Corticoesteroides/administración & dosificación , Anciano , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/inmunología , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Atrofia , Autoinmunidad , Biomarcadores/sangre , Western Blotting , Trastornos del Conocimiento/metabolismo , Trastornos del Conocimiento/terapia , Ciclofosfamida/administración & dosificación , Progresión de la Enfermedad , Electrofisiología , Femenino , Fluorodesoxiglucosa F18/metabolismo , Lóbulo Frontal/diagnóstico por imagen , Lóbulo Frontal/metabolismo , Lóbulo Frontal/patología , Hipocampo/patología , Humanos , Inmunohistoquímica , Inmunoterapia/métodos , Enfermedad por Cuerpos de Lewy/diagnóstico , Enfermedad por Cuerpos de Lewy/inmunología , Imagen por Resonancia Magnética , Neuronas/inmunología , Tomografía de Emisión de Positrones/métodos , Radiofármacos/metabolismo , Rituximab , Lóbulo Temporal/diagnóstico por imagen , Lóbulo Temporal/metabolismo , Lóbulo Temporal/patología , Resultado del TratamientoRESUMEN
BACKGROUND: Due to the ubiquitous use of cellular phones much has been speculated on secondary effects of electromagnetic irradiation emitted by those. Additionally, several studies have reported vegetative alterations as well as effects on the neuronal and molecular levels in humans. Here, using a psycho-physiological test paradigm, we examined effects of exposure to pulsed electromagnetic fields on cognitive performance. MATERIALS AND METHODS: In 11 volunteers, we tested cognitive processing under field exposure (GSM standard) and under field-free conditions. To examine the hypothesized effect of pulsed fields, we applied an auditory discrimination task and determined the participant's current 'Order Threshold' value. Following a first test cycle, the volunteers had to relax for 50 min while being, or not, exposed to pulsed electromagnetic fields. Subsequently, the test was repeated. Data acquired before and after the resting phase were compared from both experimental conditions. RESULTS: We found that nine of the 11 test participants (81.8%) showed worse results in their auditory discrimination performance upon field exposure as compared with control conditions. Group data comparison revealed a statistical significance of P = 0.0105. CONCLUSION: We could show that the participants' cognitive performance was impaired after exposure to pulsed electromagnetic fields. With regard to this finding, we recommend that the use of cellular phones should be restricted generally and in particular in respect of physical hazard of high-risk groups, e.g. elderly, children and ill people.
Asunto(s)
Encéfalo/efectos de la radiación , Teléfono Celular/normas , Trastornos del Conocimiento/etiología , Cognición/efectos de la radiación , Campos Electromagnéticos/efectos adversos , Estimulación Acústica , Adulto , Encéfalo/fisiopatología , Cognición/fisiología , Trastornos del Conocimiento/fisiopatología , Trastornos del Conocimiento/prevención & control , Aprendizaje Discriminativo/fisiología , Aprendizaje Discriminativo/efectos de la radiación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Localización de Sonidos/fisiología , Localización de Sonidos/efectos de la radiaciónRESUMEN
The influence of temperature on the performance of an enantioselective anion-exchange type chiral selector (SO) was systematically investigated. The resolution of the enantiomers of 23 N-acylated amino acids (selectands, SAs) on a covalently immobilized quinine tert.-butylcarbamate chiral stationary phase (CSP) was studied under linear chromatographic conditions over a temperature range of 0-85 degrees C with hydro-organic buffers (pHa 6.0) as mobile phases. The apparent enantioseparation factors increased considerably at low column temperatures, indicating that enthalpic contributions are the dominating thermodynamic driving force for chiral recognition for all investigated SAs. Retention factors gave non-linear van't Hoff plots, while the corresponding apparent enantioseparation factors showed linear van't Hoff behavior. Correlations between magnitude and sign of the relative thermodynamic parameters of enantioselective adsorption (deltadeltaG, deltadeltaH and deltadeltaS) and specific structural features of the analytes, i.e., steric and electronic nature of the various side chains and the N-acyl groups, are discussed with the aim to rationalize their possible contributions to the overall chiral recognition.
Asunto(s)
Aminoácidos/aislamiento & purificación , Cromatografía por Intercambio Iónico/métodos , Aminoácidos/química , Resinas de Intercambio Aniónico , Estereoisomerismo , TermodinámicaRESUMEN
Chiral drugs, agrochemicals, food additives and fragrances represent classes of compounds with high economic and scientific potential. First the present implications of their chiral nature and necessity of separating enantiomers are summarised in this article. In the following a brief overview of the actual approaches to perform enantioseparations at analytical and preparative scale is given. Challenging aspects of these strategies, such as problems associated with data management, choice of suitable chiral selectors for given enantioseparations and enhanced understanding of the underlying chiral recognition principles, are discussed. Alternatives capable of meeting the requirements of industrial processes, in terms of productivity, cost-effectiveness and environmental issues (e.g., enantioselective membranes) are critically reviewed. The impact of combinatorial methodologies on faster and more effective development and optimisation of novel chiral selectors is outlined. Finally, the merits and limitations of most recent trends in discrimination of enantiomers, including advances in the fields of sensors, microanalysis systems, chiroptical methods and chemical force microscopy are evaluated.
Asunto(s)
EstereoisomerismoRESUMEN
Four diastereomeric chiral stationary phases (CSPs) based on quinine, quinidine, epiquinine, and epiquinidine tert-butyl carbamate selectors were synthesized and evaluated under ion exchange HPLC conditions with a set of racemic N-acylated and N-oxycarbonylated alpha-amino acids as selectands. The enantioseparation potential of quinine- and quinidine-derived CSPs proved to be far superior to that of their C9-epimeric congeners. The absolute configuration of C9 stereogenic center of the cinchonan backbone of these selectors was identified as the structural feature controlling the elution order. Guided by an X-ray structure of a most favorable selector-selectand complex and the observed chromatographic enantioseparation data, a chiral recognition model was advanced. The contributions of ion-pairing, pi-pi donor-acceptor, hydrogen bonding and steric interactions were established as crucial factors.
Asunto(s)
Alcaloides de Cinchona/química , Antimaláricos/química , Carbamatos/química , Carbamatos/aislamiento & purificación , Cromatografía Líquida de Alta Presión , Alcaloides de Cinchona/aislamiento & purificación , Cristalografía por Rayos X , Modelos Químicos , Conformación Molecular , Quinidina/análogos & derivados , Quinidina/química , Quinina/análogos & derivados , Quinina/química , EstereoisomerismoRESUMEN
Behavioral flow sheets are tools that can be used outside the domain of mental health. For the knowledgeable health care provider in any setting, they render a cost-effective, noninvasive mechanism for diagnosis and management of a variety of patient problems of organic as well as behavioral natures. Though there exists an assortment of standardized formats, flow-sheet design can be tailored to address the unique circumstances of each patient. They provide an avenue for actively involving patients and families in problem assessment as well as in the planning and evaluation of treatment regimens. In addition, flow sheets provide a feedback mechanism that can enhance patient/family self-esteem and increase the likelihood of adherence to treatment recommendations. There is both an art and a science to their design and use, but the skills involved are readily acquired by any interested practitioner. The conscientious professional will become acquainted with the potential pitfalls and thus avoid irresponsible or unethical application. The authors provide guidelines for developing and implementing flow sheets and illustrate their value through the sharing of several clinical vignettes.
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Conducta , Conductas Relacionadas con la Salud , Registros de Enfermería , Terapia Conductista , Recolección de Datos , Humanos , Registros Médicos , Enfermería PrimariaRESUMEN
Waiting is inevitable for patients and families seeking health care services. Anxiety, frustration, and stress are exacerbated. A pager program, where pagers are loaned free of charge to families, uses a family-centered approach to counteract the aggravation of waiting. Patients and families can leave the hospital room or clinic setting and then be paged to return as needed. In any clinical setting, having choices and control will enhance coping and satisfaction for both patients and families.
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Niño Hospitalizado , Familia/psicología , Sistemas de Comunicación en Hospital , Listas de Espera , Adaptación Psicológica , Adulto , Niño , Humanos , Satisfacción del Paciente , Atención Dirigida al Paciente/organización & administración , Proyectos PilotoRESUMEN
Fast and efficient baseline separation of asymmetrically substituted diarylmethanols and 1,1-diarylethanols was achieved on an endcapped, amide-linked N-3,5-dinitrobenzoylated, (R,R)-1,2-diphenyl-1,2-ethanediamine-derived chiral stationary phase (CSP). Optimal enantioselectivities on this CSP were obtained using 1% 2-propanol in n-heptane as the mobile phase. Enantiorecognition was found to be governed by pi-basicity and the substitution pattern of the aromatic substituents.
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Cromatografía Líquida de Alta Presión/métodos , Etilenodiaminas/química , Metanol/análogos & derivados , Sitios de Unión , Dinitrobencenos/química , Metanol/química , Metanol/aislamiento & purificación , Estructura Molecular , EstereoisomerismoRESUMEN
A dual-wavelength heterodyne differential interferometer was developed and tested together with scanning mechanics. To extend the range of unambiguity, two wavelengths were applied. This is important for measuring structures with surface discontinuities (reliefs, steps). The automatic adjustment of the interferometer with respect to the rotational symmetrical measuring surfaces (aspheres) is important. An adjustment is needed to scan the asphere through its vertex. Typical measurements on a sphere, an asphere, and steps are shown.
RESUMEN
PURPOSE: To examine the effects of an educational intervention that teaches specialized newborn, care to substance-abusing mothers. METHOD: A quasi-experimental design included an educational intervention for a group of mothers whose babies had positive meconium stains for cocaine. Outcomes were to be assessed by the Brazelton Neonatal Behavioral Assessment Scale and Nursing Child Assessment Feeding Scale. FINDINGS: Due to a change in the hospital's discharge policy resulting in early discharge, recruitment difficulties occurred. CONCLUSION: The ramifications of this change in discharge policy are discussed.
Asunto(s)
Cuidado del Lactante/métodos , Madres/educación , Síndrome de Abstinencia Neonatal/enfermería , Estudios de Factibilidad , Femenino , Humanos , Recién Nacido , Alta del PacienteRESUMEN
On 1 November 1989 the first confirmed case of rabies in a polar bear (Ursus maritimus) was encountered by Inuit hunters in the vicinity of Cape Kendall, Southampton Island, Northwest Territories (Canada). The adult male polar bear had posterior paralysis. Rabies was detected by mouse inoculation and a positive immunoperoxidase reaction on spinal cord and Gasserian ganglion from the bear. Histologic lesions in the lumbar region of the spinal cord were consistent with the posterior paralysis. The impact of rabies on the population dynamics of polar bears probably is minimal. Rabies in polar bears constitutes a potential health hazard for polar bear hunters.
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Rabia/veterinaria , Ursidae , Animales , Antígenos Virales/análisis , Encéfalo/microbiología , Encéfalo/patología , Técnica del Anticuerpo Fluorescente , Técnicas para Inmunoenzimas , Rabia/patología , Virus de la Rabia/inmunología , Médula Espinal/microbiología , Médula Espinal/patologíaRESUMEN
Two-dimensional gel electrophoresis analysis of X0 and XY fibroblasts from a monozygotic twin pair reveals two Y-dependent polypeptides. The polypeptides have molecular weights and isoelectric points of 38,000/6.3 and 30,000/5.4 and are designated as Y-38 and Y-30.