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At present, it is not possible to reliably identify patients who will benefit from oncolytic virus treatments. Conventional modalities such as computed tomography (CT), which measure tumor size, are unreliable owing to inflammation-induced tumor swelling. We hypothesized that magnetic resonance imaging (MRI) and spectroscopy (MRS) might be useful in this regard. However, little previous data exist and neither oncolytic adenovirus nor immunocompetent models have been assessed by MRS. Here, we provide evidence that in T2-weighted MRI a hypointense core area, consistent with coagulative necrosis, develops in immunocompetent Syrian hamster carcinomas that respond to oncolytic adenovirus treatment. The same phenomenon was observed in a neuroblastoma patient while he responded to the treatment. With relapse at a later stage, however, the tumor of this patient became moderately hyperintense. We found that MRS of taurine, choline and unsaturated fatty acids can be useful early indicators of response and provide detailed information about tumor growth and degeneration. In hamsters, calprotectin-positive inflammatory cells (heterophils and macrophages) were found in abundance; particularly surrounding necrotic areas in carcinomas and T cells were significantly increased in sarcomas, when these had been treated with a granulocyte-macrophage colony-stimulating factor-producing virus, suggesting a possible link between oncolysis, necrosis (seen as a hypointense core in MRI) and/or immune response. Our study indicates that both MRI and MRS could be useful in the estimation of oncolytic adenovirus efficacy at early time points after treatment.
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Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Neuroblastoma/patología , Neuroblastoma/terapia , Viroterapia Oncolítica , Adenoviridae , Animales , Biomarcadores de Tumor/análisis , Carcinoma/patología , Carcinoma/terapia , Células Cultivadas , Colina/análisis , Cricetinae , Ácidos Grasos Insaturados/análisis , Humanos , Macrófagos/inmunología , Masculino , Necrosis , Sarcoma/patología , Sarcoma/terapia , Taurina/análisis , Resultado del TratamientoRESUMEN
We compared cognitive performance and hippocampal volumes using magnetic resonance imaging (MRI) in adult fragile-X [fra(X)] males and females with either premutation (pM) or full mutation (fM) (n = 10 in all groups). Cognitive performance of fM males in the Wechsler Adult Intelligence Scale-Revised was worse than that of pM males, and the deficits in fM females were qualitatively similar, but less severe. In a visual memory test, both fM groups were impaired. In a list learning test, fM males were impaired in the learning phase and in delayed recognition. In a logical memory test, fM males and females were not significantly different from pM subjects. Hippocampal volumes normalized for intracranial or brain area did not significantly differ between fM and pM groups. However, positive correlations between left normalized hippocampal volumes and performance in many delayed memory tests observed in pM subjects were absent in fM subjects. Furthermore, in > 50% of the fM subjects, nonspecific changes, such as enlargement of ventricles and perivascular spaces, focal hyperintensities in temporal pole white matter, and/or subjectively assessed atypical appearance of hippocampal morphology, were observed in MRI. The data suggest minor abnormalities in temporal lobe structures in adult fra(X) subjects with fM.
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Cognición , Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/psicología , Hipocampo/patología , Proteínas de Unión al ARN , Repeticiones de Trinucleótidos/genética , Adulto , ADN/análisis , ADN/sangre , Femenino , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil , Síndrome del Cromosoma X Frágil/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Memoria , Persona de Mediana Edad , Proteínas del Tejido Nervioso/genética , Pruebas Neuropsicológicas , Escalas de WechslerRESUMEN
The selection of animals for improved performance affects the profitability of pig fattening and has environmental consequences. The goal of this paper was to examine how changes in genetic and market parameters impact the biophysical (feeding patterns, timing of slaughter, nitrogen excretion) and economic (return per pig space unit) results describing pig fattening in a Finnish farm. The analysis can be viewed as focusing on terminal line breeding goals. An integrated model using recursive stochastic dynamic programming and a biological pig growth model was used to estimate biophysical results and economic values. Combining these models allowed us to provide more accurate estimates for the value of genetic improvement and, thus, provide better feedback to animal breeding programs than the traditional approach, which is based on fixed management patterns. Besides the benchmark scenario, the results were simulated for 5 other scenarios. In each scenario, genotype was improved regarding daily growth potential, carcass lean meat content, or the parameters of the Gompertz growth curve (maturing rate [], adult weight of protein [α], and adult weight of lipid mass []). The change in each parameter was equal to approximately 1 SD genetic improvement (ceteris paribus). Increasing , , daily growth potential, or carcass lean meat content increased the return on pig space unit by 12.60, 7.60, 4.10, or 2.90 per year, respectively, whereas an increase in decreased the return by 3.10. The genetic improvement in and resulted in the highest decrease in nitrogen excretion calculated in total or per kilogram of carcass gain but only under the optimal feeding pattern. Simulated changes in the Gompertz growth function parameters imply greater changes in ADG and lean meat content than changes in scenarios focusing on improving ADG and lean meat content directly. The economic value of genetic improvements as well as the quantity of nitrogen excreted during the fattening period largely depends on feeding. Improved genotypes can require changes in pig management pattern. Estimating the influence of the genotype on the nitrogen excretion without considering changes in the management pattern can result in flawed conclusions. To improve overall economic performance and to decrease the environmental footprint of fattening pig production, the pig producer can adjust the herd management pattern according to the pigs' genetics.
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Porcinos/genética , Porcinos/fisiología , Aumento de Peso/genética , Aumento de Peso/fisiología , Crianza de Animales Domésticos , Animales , Composición Corporal/genética , Ambiente , Finlandia , Genotipo , Modelos Biológicos , Nitrógeno/metabolismoRESUMEN
Adenoviruses are excellent immunotherapeutic agents with a unique ability to prime and boost immune responses. Recombinant adenoviruses cause immunogenic cancer cell death and subsequent release of tumor antigens for antigen presenting cells, resulting in the priming of potent tumor-specific immunity. This effect may be further enhanced by immune-stimulating transgenes expressed by the virus. We report a case of a 38-year-old female with Stage 3 metastatic micropapillary serous carcinoma of the ovary. She was treated in a Phase I study with a granulocyte-macrophage colony stimulating factor (GMCSF)-expressing oncolytic adenovirus, Ad5/3-D24-GMCSF (ONCOS-102). The treatment resulted in progressive infiltration of CD8+ lymphocytes into the tumor and concomitant systemic induction of several tumor-specific CD8+ T-cell populations. The patient was alive at the latest follow up more than 20 months after initiation of the study.
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BACKGROUND: Due to the progressive nature of Alzheimer's disease (AD), it has been proposed that serial imaging studies tracking the course of progression might improve the diagnostic accuracy of AD. METHODS: Longitudinal changes in hippocampal volumes were evaluated using magnetic resonance imaging (MRI) over a period of 3 years in 27 AD patients and 8 control subjects. RESULTS: A statistically nonsignificant trend towards accelerated volume loss in the AD group compared to control subjects was observed. During the study period, the average shrinkage of the hippocampal volume ranged from -2.2% to -5.8% in control subjects, and from -2.3% to -15.6% in AD patients. CONCLUSIONS: The observed changes at an individual level were small, and within the accuracy range of the measurements. Therefore, serial MRI of the hippocampus did not offer any advantage over a single MRI to support the diagnosis of AD in this study sample.
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Enfermedad de Alzheimer/diagnóstico , Hipocampo/patología , Anciano , Trastornos del Conocimiento/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Pruebas Neuropsicológicas , Índice de Severidad de la EnfermedadRESUMEN
We measured the volumes of the entorhinal, perirhinal, and temporopolar cortices on magnetic resonance images by using a recently designed histology-based protocol in 30 patients with early Alzheimer's disease (AD) and 32 healthy control subjects. Compared to the controls, all of these cortical regions were significantly atrophied in AD patients (p < 0.0001). However, the entorhinal cortex was the most severely involved brain region studied, with 40% volume loss, and this region provided the highest discriminative accuracy (92%) in separating patients with AD from healthy control subjects. Importantly, the entorhinal volume loss was evident already in mild AD. In addition, the volume of the entorhinal cortex was not dependent on age, but it did correlate significantly with the severity of the disease. Because it assesses the major site of initial neuropathological changes in AD, magnetic resonance imaging volumetric measurement of the entorhinal cortex can offer a tool for distinguishing AD patients even in the very early stages of the disease from healthy aged subjects.
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Enfermedad de Alzheimer/patología , Corteza Entorrinal/patología , Hipocampo/patología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Lóbulo Temporal/patologíaRESUMEN
In this study, magnetic resonance imaging (MRI) of the hippocampus for the diagnosis of early Alzheimer's disease (AD) is evaluated. We measured hippocampal volumes and the area of the medial hippocampus with a 1.5 T MR imager in 160 subjects: 55 patients with probable AD according to the NINCDS-ADRDA criteria, 43 subjects fulfilling the NIMH criteria of age-associated memory impairment (AAMI), 42 cognitively normal elderly controls, and 20 controls younger than 50 years. Three methods for normalization were compared. The hippocampi were atrophied in the AD patients, but not in the AAMI subjects or the elderly controls. There was no significant correlation between hippocampal volumes and age in the nondemented subjects. The discrimination based on volumetry resulted in an overall correct classification of 92% of AD patients vs. nondemented elderly subjects, whereas discrimination based on hippocampal area was less accurate, producing a correct classification in 80% of the subjects. We conclude that the hippocampus as assessed by MRI volumetry is atrophied early in AD, and spared by aging or AAMI. A brief critical review of previous studies is in concordance with the presented data: all the previous studies that have used volumetry, have similarly ended up with a good classification, whereas simpler or subjective measurements, subject to various sources of bias, have produced most variable results.
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Enfermedad de Alzheimer/clasificación , Enfermedad de Alzheimer/patología , Hipocampo/patología , Anciano , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Valor Predictivo de las Pruebas , Valores de Referencia , Caracteres SexualesRESUMEN
A prolonged MR T2 relaxation time was proposed to mark the presence and severity of Alzheimer's disease (AD). We studied the value of T2 relaxometry in diagnosing early AD. T2 was measured from 54 patients with AD, 25 subjects with age-associated memory impairment (AAMI), 18 elderly and 16 young controls. The AD patients had longer T2 in the right hippocampal head (104 +/- 11 ms) and tail (98 +/- 10 ms) than age-matched controls (95 +/- 5 and 92 +/- 9 ms, respectively). This prolongation was not related to age. In the AD group, the T2 of the left hippocampal head also correlated with the clinical severity. The T2 of the amygdala did not differ across the groups. Increased T2 in the temporal and parietal white matter and the thalamus related to increasing age rather than to the diagnostic category. The AAMI subjects had T2 comparable with those of age-matched controls. Despite the prolongation of T2 in the AD group the possible diagnostic value was compromized by a substantial overlap between the study groups. We, thus, conclude that the T2 relaxometry is not a reliable method for diagnosing early AD.
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Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/fisiopatología , Hipocampo/patología , Trastornos de la Memoria/fisiopatología , Adulto , Distribución por Edad , Anciano , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: The relationship between reduced glucose metabolism in positron emission tomography with fludeoxyglucose F 18 ([(18)F]FDG-PET) and hippocampal damage (HD) in patients with temporal lobe epilepsy is still unclear. OBJECTIVE: To determine whether the presence and severity of HD verified by quantitative magnetic resonance imaging (QMRI) and histopathological analysis affect the degree of hypometabolism. PATIENTS AND METHODS: Sixteen patients with drug-resistant temporal lobe epilepsy underwent [(18)F]FDG-PET and QMRI (hippocampal volumetry and T2 relaxometry) before surgery. Histopathological analysis of the hippocampus included measurements of neuronal loss, proliferation of glial cells, and mossy fiber sprouting. The asymmetry in glucose metabolism described the degree of hypometabolism. RESULTS: Temporal hypometabolism was not related to severity of HD as measured by QMRI or histopathological analysis. The degree of hypometabolism did not differ in patients with mild, moderate, or severe HD. In addition, [(18)F]FDG-PET revealed significant temporal hypometabolism even though hippocampal QMRI findings were normal or showed only mild HD. Thus, glucose consumption was reduced over and above the histopathological changes. CONCLUSIONS: [(18)F]FDG-PET is sensitive for localizing the epileptogenic region in patients with temporal lobe epilepsy. However, it is insensitive to reflect the severity of HD.
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Epilepsia del Lóbulo Temporal/diagnóstico , Fluorodesoxiglucosa F18 , Glucosa/metabolismo , Hipocampo/patología , Imagen por Resonancia Magnética , Tomografía Computarizada de Emisión , Adolescente , Adulto , Epilepsia del Lóbulo Temporal/metabolismo , Epilepsia del Lóbulo Temporal/cirugía , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Estadísticas no Paramétricas , Tomografía Computarizada de Emisión/métodosRESUMEN
OBJECTIVE: To analyze the frequency and severity of subclinical cerebral complications associated with coronary artery bypass grafting (CABG). DESIGN: A prospective controlled study using preoperative and postoperative magnetic resonance imaging (MRI) of the brain, quantitative electroencephalography (QEEG), and detailed neuropsychological and neurologic examinations as potentially sensitive indicators of subclinical cerebral injury associated with CABG. SETTING: Multimodality evaluation in a tertiary care unit (Kuopio University Hospital, Kuopio, Finland). PATIENTS: Thirty-eight patients undergoing elective CABG and 20 control patients undergoing other major vascular surgery, mostly operations on the abdominal aorta. MAIN OUTCOME MEASURES: Coronary artery bypass grafting-associated cerebral complications assessed preoperatively and postoperatively by brain MRI, QEEG, detailed neurologic examination, and a neuropsychological test battery that evaluates cognitive functions in major areas known to be vulnerable to organic impairment (learning and memory, attention, flexible mental processing, and psychomotor speed). RESULTS: There were no major neurologic complications. A mild hemisyndrome developed in 1 patient who underwent CABG and in 1 control patient. Overall, there was no decline in mean cognitive performance 3 months after surgery. Electroencephalographic slowing of 0.5 Hz or more in at least 2 channels occurred in 11 patients who underwent CABG and in 1 control patient (P=.03). The postoperative brain MRI scan revealed new small ischemic lesions in 8 patients (21%) in the CABG group but in none of the control group (P=.03). These new cerebral MRI lesions did not explain deterioration in neuropsychological test performance or the QEEG slowing. CONCLUSIONS: Coronary artery bypass grafting causes more QEEG alterations and small ischemic cerebral lesions that are detectable by MRI than does other major vascular surgery. The effect is mainly subclinical, because no statistically significant deterioration in mean neuropsychological test performance was detected.
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Encéfalo/patología , Puente de Arteria Coronaria/efectos adversos , Electroencefalografía/métodos , Imagen por Resonancia Magnética , Anciano , Lesiones Encefálicas/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Examen Neurológico , Pruebas Neuropsicológicas , Estudios Prospectivos , Factores de Riesgo , Procedimientos Quirúrgicos VascularesRESUMEN
OBJECTIVE: To investigate whether recurrent seizures cause hippocampal damage in temporal lobe epilepsy (TLE). PATIENTS: Eighteen patients with newly diagnosed cryptogenic TLE, 14 patients with chronic well-controlled cryptogenic TLE, 32 patients with chronic drug-resistant cryptogenic TLE, and 25 healthy subjects were studied. MEASUREMENTS: Hippocampal MRI volumetry and T2 relaxometry were used. RESULTS: Chronic drug-resistant patients with seizure focus in the left temporal lobe had an 18% smaller left hippocampus and chronic drug-resistant patients with seizure focus in the right temporal lobe had a 14% smaller right hippocampus than did the control group (p < 0.05). Chronic drug-resistant patients with seizure focus on the left side had longer T2 relaxation times in the body of the left hippocampus than did the control group (p < 0.001) and chronic drug-resistant patients with seizure focus on the right side had longer T2 relaxation times in the body of the right hippocampus than did the control subjects (p < 0.01). In all patients with a left seizure focus, the left hippocampal volume correlated inversely with the estimated total number of partial (r = -0.391, p < 0.01) or generalized (r = -0.312, p < 0.05) seizures the patient had experienced. The prolongation of the left T2 relaxation time in the body of the hippocampus correlated with the total number of both partial (r = 0.670, p < 0.001) and generalized (r = 0.481, p < 0.001) seizures and with the duration of TLE symptoms (r = 0.580, p < 0.001). CONCLUSIONS: In patients with cryptogenic epilepsy, recurrent seizures may cause damage to the hippocampus throughout the lifetime of the patient.
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Epilepsia del Lóbulo Temporal/patología , Hipocampo/patología , Adolescente , Adulto , Análisis de Varianza , Estudios de Casos y Controles , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , RecurrenciaRESUMEN
OBJECTIVE: To determine whether there is a causal link between vigabatrin treatment and concentric visual field defects and to evaluate the prevalence of these visual field constrictions. BACKGROUND: While the GABAergic antiepileptic drug (AED) vigabatrin was being clinically developed, only rare cases (less than 1:1000) of symptomatic visual field constriction and retinal disorders were reported. During 1997 to 1998, concentric visual field constrictions were described in case reports of mostly drug-resistant epilepsy patients receiving vigabatrin concurrently with other AEDs. METHODS: Ophthalmologic tests including Goldmann perimetry were performed on 32 adult patients on long-term successful vigabatrin monotherapy (treatment duration 29 to 119 months) and on 18 patients on carbamazepine monotherapy (treatment duration 32 to 108 months). Eighteen healthy adults served as controls. RESULTS: None of the patients complained about vision problems when asked to participate into the study. Thirteen out of the 32 (40%) epilepsy patients treated with vigabatrin monotherapy had concentrically constricted visual fields (9% severely, 31% mildly constricted), whereas none of the carbamazepine monotherapy patients or normal controls presented with a visual field defect (chi-square test, p = 0.0001). The extents of the visual fields were significantly constricted in vigabatrin group as compared with the visual fields of the patients in carbamazepine group or healthy controls (analysis of variance, Scheffe F-test, significant at 99%). CONCLUSIONS: The use of vigabatrin seems to increase the risk of a unique and specific pattern of bilateral, mainly asymptomatic visual field constriction. This risk should be considered when using vigabatrin. Visual field testing should also be performed before treatment and during routine follow-up for patients on vigabatrin.
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Anticonvulsivantes/uso terapéutico , Epilepsias Parciales/tratamiento farmacológico , Vigabatrin/uso terapéutico , Campos Visuales/efectos de los fármacos , Adolescente , Adulto , Análisis de Varianza , Carbamazepina/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas del Campo VisualRESUMEN
OBJECTIVE: To assess frontal lobe functions of subjects with age-associated memory impairment (AAMI) and to examine whether performance on neuropsychological tests is correlated with the volume of the frontal lobes in magnetic resonance imaging. DESIGN: Cross-sectional two-group comparison. SETTING: The Memory Research Clinic of Kuopio University and the Magnetic Resonance Imaging Center of Kuopio University Hospital. PARTICIPANTS: Ninety subjects (mean age, 70.5 years), 43 with AAMI diagnosed according to National Institute of Mental Health criteria and 47 age-matched healthy controls. MEASUREMENTS: Four neuropsychological tests were used to assess frontal lobe function: Verbal Fluency Test (VFT), Modified Wisconsin Card Sorting Test (WCST), Trail Making Test (TMT), and Stroop Test (ST). A 1.5-T magnetic resonance imager was used for volume measurements. RESULTS: The AAMI subjects scored significantly worse on the WCST, ST, and TMT compared with controls (ANCOVA, adjusted for age and education, p < 0.05). The frontal lobe volumes did not differ between AAMI subjects and controls. CONCLUSIONS: AAMI subjects appear to be impaired not only in tests assessing memory but also in tests of executive functions. This finding agrees with previous reports suggesting a central role for frontal dysfunction in memory loss of elderly people.
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Envejecimiento/psicología , Lóbulo Frontal/fisiopatología , Trastornos de la Memoria/etiología , Trastornos de la Memoria/fisiopatología , Anciano , Femenino , Lóbulo Frontal/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Trastornos de la Memoria/diagnóstico , Pruebas NeuropsicológicasRESUMEN
We analyzed hippocampal volumes and T2 relaxation times by MRI from 78 control subjects, 24 patients with temporal lobe epilepsy, and 55 patients with Alzheimer's disease (AD). In the epilepsy group, the hippocampal volumes were 27% smaller than in control subjects (p < 0.001). The T2 relaxation times were prolonged (8 to 20 ms compared with control subjects) in the head, body, and tail portions of the hippocampus on the focal side (p < 0.01) and also on the contralateral side (p < 0.05) compared with control subjects. In the epilepsy group, the prolongation of T2 relaxation time correlated inversely with the hippocampal volume (p < 0.05). In the AD group, the hippocampal volumes were 35% smaller than in control subjects (p < 0.01). The T2 relaxation times were slightly prolonged (5 to 6 ms) in the head and tail portions of the right hippocampus (p < 0.01), but the T2 relaxation times did not correlate with the hippocampal volumes. These data show that the degree of prolongation of T2 relaxation time is associated with severity of hippocampal atrophy in temporal lobe epilepsy but not in AD.
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Enfermedad de Alzheimer/patología , Epilepsia del Lóbulo Temporal/patología , Hipocampo/patología , Imagen por Resonancia Magnética , Adulto , Anciano , Atrofia , Edema Encefálico/etiología , Edema Encefálico/patología , Epilepsia del Lóbulo Temporal/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Hippocampal atrophy detected by volumetric MRI is a sensitive feature of early Alzheimer's disease (AD), but there are no studies evaluating hippocampal atrophy by MR volumetry in other dementing diseases. We therefore compared hippocampal volumes in a total of 113 subjects: 50 patients with mild to moderate AD, 9 patients with vascular dementia (VaD), 12 patients with idiopathic Parkinson's disease (PD) without dementia, 8 patients with PD and dementia (PDD), and 34 elderly control subjects. Thin, coronal, contiguous images were obtained by a 1.5-T MR imager. All patient groups had significantly smaller volumes of the hippocampus compared with the control group. In the PDD group, the absolute volumes were even smaller than in the AD group. In the PD group, the volumes were diminished to a lesser but significant extent. The volumes in the VaD group varied: of nine patients, two had no atrophy, three had unilateral, and four had bilateral atrophy. We postulate that hippocampal atrophy does not seem to be a specific phenomenon of dementia in AD but also occurs in VaD and PDD, and even in PD when no dementia is present. However, coexistence of AD pathology in our PD and VaD patients cannot be ruled out. Further studies with access to neuropathologic data are needed.
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Enfermedad de Alzheimer/patología , Demencia Vascular/patología , Demencia/complicaciones , Hipocampo/patología , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/patología , Anciano , Análisis de Varianza , Atrofia , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Valores de ReferenciaRESUMEN
Age-associated memory impairment (AAMI) is a common but disputed entity. It is unclear whether AAMI is a phenomenon of normal aging or an early sign of Alzheimer's disease. The present study aimed to identify possible structural abnormalities in the medial temporal lobe of AAMI subjects. We measured volumes of the hippocampus and amygdala by MRI in 16 AAMI subjects and in 16 age- and sex-matched controls and correlated the volumes with subjects' performance on two visual memory tasks (the Benton and the Heaton visual retention tests) and on a verbal memory task (the Buschke-Fuld Selective Reminding Test). The mean hippocampal and amygdaloid volumes normalized for brain size per se did not differ between the two study groups. In controls, but not in AAMI subjects, the right hippocampus was larger than the left. Accordingly, the volumetric asymmetry between the right and left hippocampi was smaller in AAMI subjects than in controls (Student's t test, p < 0.05). The volume of the right hippocampus (r = 0.37, n = 32, p < 0.05) and the magnitude of the asymmetry between the right and left hippocampi (r = 0.38, n = 32, p < 0.05) correlated with total score on the Benton test. We also found significant correlations between the amygdaloid volumes and the performance on visual memory tests but not with score on the verbal memory test.(ABSTRACT TRUNCATED AT 250 WORDS)
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Envejecimiento/patología , Amígdala del Cerebelo/patología , Hipocampo/patología , Imagen por Resonancia Magnética , Trastornos de la Memoria/patología , Anciano , Femenino , Humanos , Masculino , Trastornos de la Memoria/psicología , Pruebas Neuropsicológicas , Aprendizaje Verbal , Visión OcularRESUMEN
OBJECTIVE: To detect reduced [11C]flumazenil in patients with temporal lobe epilepsy (TLE) and to relate binding to histopathology. METHODS: The authors studied 16 patients who underwent epilepsy surgery because of drug-resistant TLE using [11C]flumazenil PET and quantitative MRI. In 12 patients, resected hippocampus was available for histologic analysis. [11C]Flumazenil binding potential (fitted BP) was assessed with the simplified reference tissue model. RESULTS: [11C]Flumazenil fitted BP in the medial temporal lobe was reduced in all patients with abnormal hippocampal volumetry or T2 relaxometry on MRI. Fitted BP was also reduced in 46% of the patients with hippocampal volume within the normal range and in 38% of patients with less than 2 SD T2 prolongation. In all MRI-negative/PET-positive patients, the histologic analysis verified hippocampal damage. Also, [11C]flumazenil fitted BP correlated with the severity of reduced hippocampal volume, T2 prolongation, and histologically assessed neuronal loss and astrogliosis. CONCLUSION: [11C]Flumazenil PET provides a useful tool for investigating the hippocampal damage in vivo even in patients with no remarkable hippocampal abnormalities on quantitative MRI.
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Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Flumazenil/farmacocinética , Hipocampo/metabolismo , Lóbulo Temporal/metabolismo , Adolescente , Adulto , Anticonvulsivantes/uso terapéutico , Benzodiazepinas/uso terapéutico , Epilepsia del Lóbulo Temporal/diagnóstico , Epilepsia del Lóbulo Temporal/terapia , Femenino , Moduladores del GABA/farmacocinética , Hipocampo/diagnóstico por imagen , Hipocampo/patología , Hipocampo/cirugía , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Lóbulo Temporal/diagnóstico por imagen , Lóbulo Temporal/patología , Tomografía Computarizada de Emisión , Resultado del Tratamiento , Ácido Valproico/uso terapéutico , Vigabatrin/uso terapéuticoRESUMEN
Hippocampal volume measurements using magnetic resonance imaging (MRI) and assessment of performance in tests of delayed recall are among the most useful aids for diagnosing early Alzheimer's disease (AD) on an individual level. However, their comparative diagnostic accuracy has not been previously addressed. In this study we compared the diagnostic accuracy of these two methods in 57 patients with probable AD according to the NINCDS-ADRDA criteria, and 34 age- and gender-matched control subjects. The discriminatory power of the hippocampal volumes and delayed recall performance, Russel's Adaptation of the Visual Reproduction Test (VRT), were compared in discrimination function and receiver operator characteristic analyses. Right and left hippocampal volumes resulted in correct classification of 85.7-86.8% of the study subjects, respectively, while performance in the VRT resulted in correct classification of 93.4% of subjects. The area under curve value was 0.93 for the left hippocampus and 0.96 for the VRT. These data suggest that assessment of delayed recall with the VRT is of high diagnostic accuracy, and may surpass the diagnostic accuracy of hippocampal volumetry.
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Enfermedad de Alzheimer/diagnóstico , Hipocampo/patología , Recuerdo Mental , Adaptación Psicológica/fisiología , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/psicología , Reacciones Falso Positivas , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Escalas de Valoración Psiquiátrica , Caracteres Sexuales , Percepción Visual/fisiologíaRESUMEN
An increased frequency of apolipoprotein E E4 allele has been reported in patients with late onset Alzheimer's disease. Apolipoprotein E participates in the transport of cholesterol and other lipids and interferes with the growth and regeneration of both peripheral and central nervous system tissues during development and after injury. Apolipoprotein E is also implicated in synaptogenesis. Apolipoprotein E isoforms differ in binding to amyloid-beta-protein and tau protein in vitro. Here, we wanted to study the effect of apolipoprotein E genotype on the magnitude of damage in the hippocampus, where a marked synapse loss exists in Alzheimer's disease. We measured by magnetic resonance imaging the volumes of the hippocampus, amygdala, and frontal lobes in the three Alzheimer subgroups: patients with 2, 1 or 0 E4 alleles. We also investigated the profile of deficits on tests assessing memory, language, visuospatial, executive, and praxic functions of these Alzheimer subgroups. All Alzheimer patients were at early stage of the disease. We found that Alzheimer patients with E4/4 genotype (N = 5) had smaller volumes of the hippocampus and the amygdala than those with E3/4 (N = 9) and those with E3/3 or E2/3 (N = 12). The difference was significant for the right hippocampus (-54% of control) and the right amygdala (-37% of control). The volumes of the frontal lobes were similar across the Alzheimer subgroups. The patients with E4/4 also showed lowest scores on delayed memory tests and differed from E3/3, 3/2 patients in the list learning test (< 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/patología , Amígdala del Cerebelo/patología , Apolipoproteínas E/genética , Lóbulo Frontal/patología , Hipocampo/patología , Anciano , Enfermedad de Alzheimer/psicología , Cognición/fisiología , Enzimas de Restricción del ADN , Femenino , Genotipo , Humanos , Imagen por Resonancia Magnética , Masculino , Memoria/fisiología , Reacción en Cadena de la PolimerasaRESUMEN
Time-density curves of the liver and spleen from dynamic CT-scans, performed on ten patients with liver cirrhosis and 15 patients with fatty liver were compared with 41 normal cases. After the intravenous bolus injection of urographic contrast medium (18.5 g I), six scans per minute for 2 minutes and single scans at 3, 4, and 5 minutes were executed. In patients with fatty liver the curves of the liver and spleen did not differ from those in the normal patients. In liver cirrhosis the peak contrast enhancement of both liver and spleen was lower and delayed and the washout phases slower. The results indicate that the patterns of the time-density curves of the liver and spleen may contain diagnostic information in liver cirrhosis.