RESUMEN
INTRODUCTION: Training in Affect Recognition (TAR) is a "targeted" and computer-aided program that has been shown to effectively attenuate facial affect recognition deficits and improve social functioning in patients with schizophrenia. Social Cognition and Interaction Training (SCIT) is a group "broad-based" intervention, that has also been shown to improve emotion recognition, theory of mind (ToM), and social functioning. To date, no study has compared the efficacy of two different social cognitive interventions. OBJECTIVES: We aim to compare the efficacy of TAR and SCIT on schizophrenia patients' performance on facial affect recognition, theory of mind, attributional style and social functioning before, after treatment, and three months thereafter. METHODS: One hundred outpatients with a diagnosis of schizophrenia were randomly assigned to the TAR or SCIT condition and completed pre- (T0) and posttreatment (T1) assessments and a 3-month follow up (T2) of emotion recognition (ER-40), theory of mind (Hinting Task), attributional style (AIHQ) and social functioning (PSP). RESULTS: The entire sample, receiving TAR or SCIT, showed improvements in theory of mind, attributional style, clinical symptoms and social functioning. This effect was maintained at three-months. The TAR intervention was more efficacious than the SCIT program in improving the recognition of facial emotions (ER-40). The TAR intervention also demonstrated a lower drop-out rate than the SCIT intervention. CONCLUSIONS: There were improvements in social cognition, symptomatology and functioning of patients in the entire sample, receiving SCIT or TAR. Both TAR and SCIT appear as valuable treatments for people with schizophrenia and social cognitive deficits.
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Terapia Cognitivo-Conductual , Esquizofrenia , Teoría de la Mente , Cognición , Emociones , Humanos , Relaciones Interpersonales , Esquizofrenia/terapia , Cognición Social , Percepción SocialRESUMEN
Newborn screening (NBS) for Krabbe disease, a rare neurodegenerative disorder caused by deficient galactocerebrosidase (GALC) enzyme activity, has recently been implemented in a number of US states. However, the spectrum of phenotypic manifestations associated with deficient GALC activity complicates the management of screen-positive newborns and underscores the need to identify clinically relevant biomarkers. Earlier studies with a small number of patients identified psychosine, a substrate of the GALC enzyme, as a potential biomarker for Krabbe disease. In this study, we provide, for the first time, longitudinal data on dried blood spot (DBS) psychosine concentrations in different Krabbe disease phenotypes for both untreated patients and those treated with hematopoietic stem cell transplantation (HSCT). Our cohort included patients previously identified by NBS to be at high risk to develop Krabbe disease. Substantially elevated DBS psychosine concentration during the newborn period was found to be a highly specific marker for infantile Krabbe disease. This finding supports the use of DBS psychosine concentration as a second-tier NBS test to aid in the identification of patients who require urgent evaluation for HSCT. In addition, longitudinal assessments showed that both natural disease progression and treatment with HSCT were associated with decreases in DBS psychosine concentrations. Based on these findings we provide recommendations for the interpretation of psychosine concentrations in DBS specimens collected during the first year of life. Future studies should aim to better delineate the relationship between DBS psychosine concentration and disease onset in patients with later-onset forms of Krabbe disease.
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Biomarcadores/sangre , Leucodistrofia de Células Globoides/diagnóstico , Psicosina/sangre , Adolescente , Niño , Preescolar , Progresión de la Enfermedad , Pruebas con Sangre Seca , Humanos , Lactante , Recién Nacido , Leucodistrofia de Células Globoides/tratamiento farmacológico , Tamizaje Neonatal , Fenotipo , Espectrometría de Masas en TándemRESUMEN
BACKGROUND: Krabbe disease is a fatal neurodegenerative disease caused by rapid demyelination of the central and peripheral nervous systems. The only available treatment, unrelated umbilical cord blood transplantation, is effective only if performed before clinical symptoms appear. Phenotypic expressions of disease-causing mutations vary widely, but genotype-phenotype relationships are unclear. Therefore, we evaluated diffusion tensor imaging (DTI) tractography with volumetric analysis as a biomarker of early white matter changes and functional disability in presymptomatic infants. METHODS: We obtained DTI and structural scans of newborns with early-infantile Krabbe disease (n = 9) diagnosed by family history or newborn screening. We compared white matter fiber tract properties to those of normal controls (n = 336) and assessed the ability of tract-based properties to predict longitudinal development in four functional domains (cognitive, fine motor, gross motor, adaptive behavior) after treatment with unrelated umbilical cord blood transplantation. We also assessed the relationship between the standard evaluation (modified Loes score) and DTI results, and the volumetric differences between the Krabbe subjects and normal controls. FINDINGS: Reductions in fractional anisotropy were significant in the corticospinal tract in the Krabbe patients compared to controls, which strongly correlated with motor and cognitive outcomes after transplantation. Significant regional differences were observed in the splenium and uncinate fasciculus in Krabbe patients and these differences correlated only with cognitive outcomes. Regional brain volumes of Krabbe patients were slightly larger than controls. Loes scores did not correlate with DTI results. INTERPRETATION: Neonatal microstructural abnormalities correlate with neurodevelopmental treatment outcomes in patients treated for infantile Krabbe disease. DTI with quantitative tractography is an excellent biomarker for evaluating infants with Krabbe disease identified through newborn screening.
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Encéfalo/patología , Desarrollo Infantil , Interpretación de Imagen Asistida por Computador/métodos , Leucodistrofia de Células Globoides/patología , Vías Nerviosas/patología , Trasplante de Células Madre de Sangre del Cordón Umbilical , Imagen de Difusión Tensora , Femenino , Humanos , Recién Nacido , Leucodistrofia de Células Globoides/terapia , Imagen por Resonancia Magnética , Masculino , Resultado del Tratamiento , Sustancia Blanca/patologíaRESUMEN
Alpha-mannosidosis is a rare lysosomal storage disease. Hematopoietic SCT (HSCT) is usually recommended as a therapeutic option though reports are anecdotal to date. This retrospective multi institutional analysis describes 17 patients that were diagnosed at a median of 2.5 (1.1-23) years and underwent HSCT at a median of 3.6 (1.3-23.1) years. In all, 15 patients are alive (88%) after a median follow-up of 5.5 (2.1-12.6) years. Two patients died within the first 5 months after HSCT. Of the survivors, two developed severe acute GvHD (>=grade II) and six developed chronic GvHD. Three patients required re-transplantation because of graft failure. All 15 showed stable engraftment. The extent of the patients' developmental delay before HSCT varied over a wide range. After HSCT, patients made developmental progress, although normal development was not achieved. Hearing ability improved in some, but not in all patients. We conclude that HSCT is a feasible therapeutic option that may promote mental development in alpha-mannosidosis.
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Trasplante de Células Madre Hematopoyéticas/métodos , alfa-Manosidosis/terapia , Adolescente , Adulto , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Oncología Médica/métodos , Estudios Retrospectivos , Trasplante Homólogo/métodos , Resultado del TratamientoRESUMEN
BACKGROUND AND PURPOSE: Reliable markers for predicting neurologic outcome in patients with MPS II are lacking. The purpose of this study is to explore whether quantitative volumetric measurements of brain MR imaging can be used to differentiate between MPS II patients with and without cognitive impairment. This MR imaging study is the first in MPS II patients to use automated/semi-automated methods to quantify brain volumes in a longitudinal design. MATERIALS AND METHODS: Sixteen male patients with MPS II in a natural history study had annual brain MR imaging and detailed neurodevelopmental assessment over 2 years. Automated and semi-automated methods were used to determine brain volumes. Linear mixed regression models adjusting for age were used to assess the correlation between the volumetric parameters and cognition. RESULTS: Among the 16 MPS II patients, 10 (22 MR imaging studies) had cognitive impairment whereas the other 6 (11 MR imaging studies) had normal cognition. A decreased brain tissue/ICV ratio (-5%; P < .001) and an increased lateral ventricle/ICV ratio (+4%; P = .029) were found in patients with cognitive impairment compared with patients with normal cognition. These changes were apparent in patients as young as 7 years of age in addition to older patients. CONCLUSIONS: Quantitative volumetric measurements of brain MR imaging in MPS II patients can be obtained by using automated and semi-automated segmentation methods. MPS II patients with cognitive impairment have decreased brain tissue volumes, but longer studies with more subjects are required to confirm these results.
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Encéfalo/patología , Trastornos del Conocimiento/patología , Imagen por Resonancia Magnética/métodos , Mucopolisacaridosis II/patología , Adolescente , Adulto , Atrofia , Niño , Preescolar , Trastornos del Conocimiento/etiología , Progresión de la Enfermedad , Humanos , Estudios Longitudinales , Masculino , Mucopolisacaridosis II/complicaciones , Valor Predictivo de las Pruebas , Análisis de Regresión , Adulto JovenRESUMEN
Hunter syndrome is a rare, X-linked disorder caused by a deficiency of the lysosomal enzyme iduronate-2-sulfatase. In the absence of sufficient enzyme activity, glycosaminoglycans accumulate in the lysosomes of many tissues and organs and contribute to the multisystem, progressive pathologies seen in Hunter syndrome. The nervous, cardiovascular, respiratory, and musculoskeletal systems can be involved in individuals with Hunter syndrome. Although the management of some clinical problems associated with the disease may seem routine, the management is typically complex and requires the physician to be aware of the special issues surrounding the patient with Hunter syndrome, and a multidisciplinary approach should be taken. Subspecialties such as otorhinolaryngology, neurosurgery, orthopedics, cardiology, anesthesiology, pulmonology, and neurodevelopment will all have a role in management, as will specialty areas such as physiotherapy, audiology, and others. The important management topics are discussed in this review, and the use of enzyme-replacement therapy with recombinant human iduronate-2-sulfatase as a specific treatment for Hunter syndrome is presented.
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Conducta Cooperativa , Terapia de Reemplazo Enzimático , Trasplante de Células Madre Hematopoyéticas , Iduronato Sulfatasa/efectos adversos , Comunicación Interdisciplinaria , Mucopolisacaridosis II/terapia , Grupo de Atención al Paciente , Adolescente , Adulto , Niño , Preescolar , Terapia Combinada , Genotipo , Humanos , Lactante , Recién Nacido , Infusiones Intravenosas , Masculino , Mucopolisacaridosis II/genética , Fenotipo , Ensayos Clínicos Controlados Aleatorios como Asunto , Proteínas Recombinantes/administración & dosificación , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: It is not possible to determine if neonates diagnosed with Krabbe disease through statewide neonate screening programs will develop the disease as infants, juveniles, or adults. The only available treatment for this fatal neurodegenerative condition is unrelated umbilical cord transplantation, but this treatment is only effective before clinical symptoms appear. Therefore, a marker of disease progression is needed. The purpose of this study was to evaluate the use of diffusion tensor imaging (DTI) with fiber tracking in identifying early changes in major motor tracts of asymptomatic neonates with infantile Krabbe disease. MATERIALS AND METHODS: Six neonates with infantile Krabbe disease identified because of family history underwent brain MR imaging within the first 4 weeks of life. Six-direction DTI and quantitative tractography of the corticospinal tracts were performed. Hypothesis tests, 1 for each hemisphere, were used to determine whether the fractional anisotropy (FA) ratio of the neonates with infantile Krabbe disease was significantly different from that of 45 age- and sex-matched controls. RESULTS: The average FA ratio for patients with Krabbe disease was 0.89 and 0.87 for left and right tracts, respectively (P = .002 and < .001). After adjusting for gestational age, gestational age at birth, birth weight, sex, and race, the 6 patients with Krabbe disease had significantly lower FA values than the controls (P < .001). CONCLUSIONS: DTI with quantitative tractography detected significant differences in the corticospinal tracts of asymptomatic neonates who had the early-onset form of Krabbe disease. Once standardized and validated, this tool has the potential to be used as a marker of disease progression in neonates diagnosed through statewide neonate screening programs.
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Imagen de Difusión por Resonancia Magnética/métodos , Leucodistrofia de Células Globoides/patología , Fibras Nerviosas Mielínicas/patología , Tractos Piramidales/patología , Enfermedades de la Médula Espinal/patología , Femenino , Humanos , Recién Nacido , MasculinoRESUMEN
OBJECTIVE: Describe the morphological changes that take place in the lung parenchyma and in the airways during the respiratory cycle with a view to establishing a relationship between them. SUBJECTS: Adult Wistar rats. INTERVENTIONS: The lungs were fixed at seven different points in the respiratory cycle: Inflation, 10 and 20 cm. transpulmonary pressure, total lung capacity. Deflation, 20, 15, 10 and 0 cm transpulmonary pressure. MEASUREMENTS: The lungs were processed for morphometric study and bronchial and parenchymal variables, such as lung volume, number of alveoli, anatomic dead space, bronchial lumen surface and bronchial wall surface were quantified. The results were compared by analysis of variance (ANOVA) or the Kruskal-Wallis and Mann-Whitney's U tests. RESULTS: The lung volume, the number of alveoli and the anatomic dead space increased with the increase of the transpulmonary pressure and decreased with the decrease of it, the obtained values in deflation being higher than those in inflation (p<0.05). The bronchial lumen and the bronchial wall surfaces generally showed higher values in inflation than in deflation (p<0.05). CONCLUSIONS: The anatomic dead space was altered as a consequence of the variations in airway diameter and length. Lung parenchyma tension may have been of influence in the variations of the bronchial wall.
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Pulmón/anatomía & histología , Pulmón/patología , Alveolos Pulmonares/patología , Respiración , Sistema Respiratorio , Animales , Bronquios/patología , Mediciones del Volumen Pulmonar , Masculino , Presión , Ratas , Ratas WistarRESUMEN
The resistance to airflow that develops in most obstructive processes takes place in the small airways. The aim of the present paper is to describe bronchial hysteresis morphometrically in a respiratory cycle model. As a working hypothesis, it is proposed that the changes that take place in the respiratory tract during the respiratory cycle are related to the bronchial size. Specimen rat lungs were organized into five groups: In the first group, the lungs were filled with a liquid fixative to 25 cm of H2O transpulmonary pressure. The following four groups were inflated with air and fixed through the pulmonary artery. Groups 2 and 3 were fixed at 10 and 20 cm transpulmonary pressure in inflation. The last two groups were fixed in deflation and, for this purpose, the transpulmonary pressure was increased to 27 cm and decreased to 20 and 10 cm, respectively. The lungs were processed for morphometrical study and the following variables were quantified: pulmonary volume, internal area, internal perimeter, wall area, internal area radius and bronchial wall radius. The diameter of the airways studied varied between 84.06 microm and 526.4 microm. The results were classified into three subgroups consisting of small, medium-sized and large bronchi. With a single exception--the internal area in the medium-sized bronchi inflated to 20 cm--all the results obtained in deflation were higher than those obtained in inflation. The internal area increased or decreased significantly upon raising or lowering the transpulmonary pressure respectively, in the small and medium-sized bronchi. The wall area in the large bronchi showed significant differences between inflation and deflation at 10 and 20 cm transpulmonary pressure. The wall area was modified significantly in the lungs fixed at 20 cm in the small bronchi and at 10 cm in medium-sized bronchi. The bronchial wall radius was significantly greater in the large bronchi and smaller in the small bronchi. The lumen of the medium-sized and small bronchi increases in inspiration and decreases in expiration. The wall thickness displayed differences between inflation and deflation. The most marked hysteresis was presented by the bronchial wall in the large bronchi. Our results suggest that the behavior of the bronchi varies according to their size.
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Bronquios/citología , Respiración , Animales , Bronquios/fisiología , Broncoconstricción/fisiología , Femenino , Citometría de Imagen , Masculino , Modelos Animales , Ratas , Ratas Endogámicas F344RESUMEN
Se realiza una revisión y puesta al día de las necesidades nutritivas del recién nacido pretérmino. Se analizan los diversos nutrientes y las recomendaciones de diferentes organismos y publicaciones internacionales, con especial referencia a los ácidos grasos insaturados de cadena larga y su importancia en los niños prematuros. Finalmente, se describe el protocolo que el servicio de Neonatología tiene establecido para la alimentación en estos niños (AU)
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Femenino , Masculino , Humanos , Recién Nacido , Recien Nacido Prematuro/fisiología , Ácidos Grasos Insaturados/administración & dosificación , Ácidos Grasos Insaturados/uso terapéutico , Protocolos Clínicos , Necesidades Nutricionales , Agua/administración & dosificación , Proteínas/administración & dosificación , Grasas/administración & dosificación , Grasas/uso terapéutico , Sodio en la Dieta/administración & dosificación , Potasio en la Dieta/administración & dosificación , Minerales en la Dieta/administración & dosificación , Vitaminas en la Dieta/administración & dosificación , Vitaminas en la Dieta/uso terapéutico , Fenómenos Fisiológicos Nutricionales del Lactante/educación , Fenómenos Fisiológicos de la Nutrición/educación , Recién Nacido Pequeño para la Edad Gestacional/fisiología , Recién Nacido de Bajo Peso/fisiología , Nutrición Parenteral/métodos , Electrólitos/administración & dosificaciónRESUMEN
HYPOTHESIS: The changes in pulmonary volume taking place during respiration are accompanied by the opening and closing of the alveoli, with the number of alveoli open, at the same transpulmonary pressure (TPP) differing, depending on whether the lung is insufflated or deflated. MATERIAL AND METHODS: Seventy 344 Fischer rats divided into five groups. Group 1 lungs were fixed by instilling 10% formalin through the trachea to a pressure of 25 cm H2O. The lungs of the next four groups were air-filled and fixed via the pulmonary artery: group 2 lungs were fixed in inflation at 10 cm H2O TPP; group 3 lungs were fixed in inflation at 20 cm. H2O TPP; the lungs of groups 4 and 5 were fixed in deflation and, therefore, were inflated with air up to 27 cm. H2O to drop to 20 cm in group 4 and to 10 cm in group 5. The lungs were processed for light microscopy, carrying out a morphometric study. The results were statistically processed. RESULTS: The lungs insufflated with liquid fixative at 25 cm of TPP reached higher values in the variables Pulmonary Volume, Internal Alveolar Surface (IAS) and Number of Alveoli, being statistically significant (p < 0.05) in comparison with the other four groups. In the lungs fixed in deflation, the pulmonary volume, IAS and number of alveoli were greater than in those fixed in inflation. The lungs fixed to 20 cm in deflation displayed significant statistical differences compared with those fixed to 20 cm in inflation. The IAS and number of alveoli gave good rates in relation with the pulmonary volume (r > or = 0.65). Three variables were used to measure the size of the alveoli, alveolar cord, alveolar surface and Lm, but none showed significant modifications. CONCLUSION: This study supports the hypothesis that changes in lung volume are related to the increase/decrease in the number of alveoli that are open/closed and not to the modification in the size of the alveoli. Alveolar recruitment is the microscopic expression of pulmonary hysteresis, since the number of alveoli open in deflation is greater than the number open during inflation.
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Modelos Anatómicos , Alveolos Pulmonares/fisiología , Ventilación Pulmonar/fisiología , Presión Esfenoidal Pulmonar/fisiología , Animales , Mediciones del Volumen Pulmonar , Modelos Animales , Ratas , Ratas Endogámicas F344RESUMEN
A simple, sensitive and reproducible high-performance liquid chromatographic method for detecting and quantifying saquinavir in human plasma is described. Verapamil was used as internal standard. The method employes a single liquid-liquid extraction step with tert-butil methyl ether followed by chromatography on a Lichrospher 60 Select B C8 reversed-phase column. Ultraviolet detection was used to identify the compounds of interest. The quantitation limit of saquinavir was 1 ng/mL and only 0.5 mL of plasma sample was required for the determination. The average saquinavir recoveries over a concentration range of 2.5-500 ng/mL ranged from 86 to 95%. Precision and accuracy did not exceed 5%.
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Cromatografía Líquida de Alta Presión/métodos , Infecciones por VIH/sangre , Inhibidores de la Proteasa del VIH/sangre , Saquinavir/sangre , Calibración , Interacciones Farmacológicas , Infecciones por VIH/tratamiento farmacológico , Humanos , Estándares de Referencia , Espectrofotometría UltravioletaAsunto(s)
Antibacterianos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Cetólidos , Macrólidos , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Antibacterianos/efectos adversos , Antibacterianos/química , Antibacterianos/farmacocinética , Bacterias/efectos de los fármacos , Ensayos Clínicos Fase III como Asunto , Contraindicaciones , Interacciones Farmacológicas , Humanos , Síndrome de QT Prolongado/inducido químicamente , Estructura Molecular , Resultado del TratamientoRESUMEN
It is well to assume that bioanalytical chromatographic methods for the determination of polar basic drugs are developed and optimised according to a standardised procedure which involves two alternatives: (a) modifications in the sample preparation procedures, and (b) changes in the stationary phase of the chromatographic system. In this paper, a simple and rapid chromatographic procedure using a specific analytical detection method (ESI tandem mass spectrophotometric detection) in combination with a fast and efficient sample work-up procedure, protein precipitation, is presented. A demonstration of the entire chromatographic procedure is given for an HPLC method for the determination of famotidine in human plasma, a basic polar drug with poor solubility in organic solvents. In order to optimize the mass detection of famotidine, several parameters such as ionization mode, fragmentor voltage, m/z ratios of ions monitored, type of organic modifier and eluent additive, were investigated. Each analysis required 5 min. The calibration curve of famotidine in the range 1-200 ng/ml was linear with a correlation coefficient of 0.9992 (n = 6), and a detection limit a signal-to-noise ratio of 3 was approximately 0.2 ng/ml. The within- and between-day variations in the famotidine analysis were 5.2 (n = 6) and 6.7% (n = 18), respectively. The applicability of this method was also demonstrated for the analysis of plasma samples in a Phase-I human pharmacokinetic study.