[Memory deficit in patients with subcortical vascular cognitive impairment versus Alzheimer-type dementia: the sensitivity of the 'word list' subtest on the Wechsler Memory Scale-III]. / Déficit de memoria en pacientes con deterioro cognitivo vascular subcortical frente a demencia tipo Alzheimer: sensibilidad del subtest 'lista de palabras' de la escala de memoria de Wechsler-III.

INTRODUCTION: Memory deficits are frequent in mild subcortical vascular pathology and in the early stage of Alzheimer's disease. AIM: To study the memory deficits in patients with subcortical vascular cognitive impairment (SVCI) vs. mild stage Alzheimer's disease patients (AD), using the Weschler Memory Scale-III (WMS-III) word lists test, to examine the adequacy of this test to show the different memory patterns in this population, that could contribute to early differential diagnosis. PATIENTS AND METHODS: Three groups of patients were compared: AD (n = 25), SVCI-leukoaraiosis (n = 17) and SVCI-multi infarct (n = 16). The three groups did not differ in age, education or severity of illness. RESULTS: Patients with SVCI showed a memory impairment in free recall with an improvement in their performance on the recognition task. The AD group, however, showed low scores in free recall as in recognition tasks, with a major number of false positive errors. Significant differences were also found between the SVCI-leukoaraiosis and SVCI-multi infarct groups, with the latter showing the best performance in long term retention and a minor trend to respond with false positive errors. CONCLUSIONS: The WMS-III word lists test is a good instrument to differentiate the memory profile between SVCI and AD, with the recognition task being the most discriminative one. The worst impairment in leukoaraiosis patients in comparison to the multi infarct group, suggests that white matter diffuse lesion could affect more directly the recall processes mediatised by the frontal lobe.

Déficit de memoria en pacientes con deterioro cognitivo vascular subcortical frente a demencia tipo Alzheimer: sensibilidad del subtest ‘lista de palabras’ de la escala de memoria de Wechsler-III / Memory deficit in patients with subcortical vascualr cognitive impairment versus alzheimer type dementia: The sensitivity of the "Word list subtest on the wechsler memory scale-III"

Resumen. Introducción. Los déficit de memoria son frecuentes en la patología vascular subcortical y en la fase inicial de la enfermedad de Alzheimer. Objetivo. Estudiar los déficit de memoria, mediante el subtest ‘lista de palabras’ de la escala de memoria de Weschler-III (WMS-III), de pacientes con deterioro cognitivo vascular subcortical (DCVS) frente a demencia tipo Alzheimer (DTA) en fases tempranas, con el fin de estudiar la posible utilidad de esta prueba para mostrar patrones diferenciados de deterioro mnésico, que podrían ser de ayuda en el diagnóstico precoz. Pacientes y métodos. Se compararon tres grupos de pacientes: DTA (n = 25), DCVS-leucoaraiosis (n = 17) y DCVS-multiinfarto (n = 16). No había diferencias significativas entre los tres grupos en cuanto a edad, características socioculturales y gravedad del déficit cognitivo. Resultados. Los pacientes con DCVS mostraron una alteración en el recuerdo libre y una mejora en su rendimiento en el reconocimiento. Por el contrario, pacientes con DTA mostraron un recuerdo libre y un reconocimiento alterados, este último con numerosos falsos positivos. Se encontraron diferencias entre los dos grupos con DCVS-leucoaraiosis y DCVS-multiinfarto. Estos últimos mostraron un menor deterioro en la retención a largo plazo. Conclusiones. En este estudio, el subtest ‘lista de palabras’ de la WMS-III demuestra ser una prueba sensible para diferenciar el patrón mnésico entre DTA y DCVS, y el reconocimiento es la medida más discriminativa del subtest. El mayor deterioro en los pacientes con leucoaraiosis, respecto a los pacientes con multiinfarto, sugiere que la afectación difusa de la substancia blanca afecta más directamente a los procesos de recuperación en que está implicado el lóbulo frontal(AU)

Summary. Introduction. Memory deficits are frequent in mild subcortical vascular pathology and in the early stage of Alzheimer’s disease. Aim. To study the memory deficits in patients with subcortical vascular cognitive impairment (SVCI) vs. mild stage Alzheimer’s disease patients (AD), using the Weschler Memory Scale-III (WMS-III) word lists test, to examine the adequacy of this test to show the different memory patterns in this population, that could contribute to early differential diagnosis. Patients and methods. Three groups of patients were compared: AD (n = 25), SVCI-leukoaraiosis (n = 17) and SVCI-multi infarct (n = 16). The three groups did not differ in age, education or severity of illness. Results. Patients with SVCI showed a memory impairment in free recall with an improvement in their performance on the recognition task. The AD group, however, showed low scores in free recall as in recognition tasks, with a major number of false positive errors. Significant differences were also found between the SVCI-leukoaraiosis and SVCI-multi infarct groups, with the latter showing the best performance in long term retention and a minor trend to respond with false positive errors. Conclusions. The WMS-III word lists test is a good instrument to differentiate the memory profile between SVCI and AD, with the recognition task being the most discriminative one. The worst impairment in leukoaraiosis patients in comparison to the multi infarct group, suggests that white matter diffuse lesion could affect more directly the recall processes mediatised by the frontal lobe (AU)

Screening for novel antimicrobials from encoded combinatorial libraries by using a two-dimensional agar format.

A sensitive lawn-based format has been developed to screen bead-tethered combinatorial chemical libraries for antimicrobial activity. This method has been validated with beads linked to penicillin V via a photocleavable chemical linker in several analyses including a spike-and-recover experiment. The lawn-based screen sensitivity was modified to detect antibacterial compounds of modest potency, and a demonstration experiment with a naive combinatorial library of over 46,000 individual triazines was evaluated for antibacterial activity. Numerous hits were identified, and both active and inactive compounds were resynthesized and confirmed in traditional broth assays. This demonstration experiment suggests that novel antimicrobial compounds can be easily identified from very large combinatorial libraries of small, nonpeptidic compounds.

Light-generated oligonucleotide arrays for rapid DNA sequence analysis.

In many areas of molecular biology there is a need to rapidly extract and analyze genetic information; however, current technologies for DNA sequence analysis are slow and labor intensive. We report here how modern photolithographic techniques can be used to facilitate sequence analysis by generating miniaturized arrays of densely packed oligonucleotide probes. These probe arrays, or DNA chips, can then be applied to parallel DNA hybridization analysis, directly yielding sequence information. In a preliminary experiment, a 1.28 x 1.28 cm array of 256 different octanucleotides was produced in 16 chemical reaction cycles, requiring 4 hr to complete. The hybridization pattern of fluorescently labeled oligonucleotide targets was then detected by epifluorescence microscopy. The fluorescence signals from complementary probes were 5-35 times stronger than those with single or double base-pair hybridization mismatches, demonstrating specificity in the identification of complementary sequences. This method should prove to be a powerful tool for rapid investigations in human genetics and diagnostics, pathogen detection, and DNA molecular recognition.

Light-directed, spatially addressable parallel chemical synthesis.

Solid-phase chemistry, photolabile protecting groups, and photolithography have been combined to achieve light-directed, spatially addressable parallel chemical synthesis to yield a highly diverse set of chemical products. Binary masking, one of many possible combinatorial synthesis strategies, yields 2n compounds in n chemical steps. An array of 1024 peptides was synthesized in ten steps, and its interaction with a monoclonal antibody was assayed by epifluorescence microscopy. High-density arrays formed by light-directed synthesis are potentially rich sources of chemical diversity for discovering new ligands that bind to biological receptors and for elucidating principles governing molecular interactions. The generality of this approach is illustrated by the light-directed synthesis of a dinucleotide. Spatially directed synthesis of complex compounds could also be used for microfabrication of devices.

Time-resolved pulsed fluorescence immunometric assays of carcinoembryonic antigen.

A time-resolved pulsed fluorescence immunometric assay (TR-PFIA) for carcinoembryonic antigen is described in which either Eu(III) or Tb(III) chelate is used as label. Described in detail is the assay involving the well-documented format of microtiter matrix and Eu(III) fluorescence enhanced with a beta-diketone and quantified in a commercial time-resolving fluorometer. We have also used the same basic assay, but one with a Tb(III) chelate as label, and we read the fluorescence signal directly off a surface without the application of enhancement solution. The Tb(III) fluorescence is then brought into solution by using an analog of dipicolinic acid in an enhancement solution. The latter approach demonstrates the scope of the methodology, which invokes the extra complexity of enhancement only when increased sensitivity might be required. The power and versatility of the enhancement methodology are demonstrated.