Preclinical trials in autosomal dominant AD: implementation of the DIAN-TU trial.

The Dominantly Inherited Alzheimer's Network Trials Unit (DIAN-TU) was formed to direct the design and management of interventional therapeutic trials of international DIAN and autosomal dominant Alzheimer's disease (ADAD) participants. The goal of the DIAN-TU is to implement safe trials that have the highest likelihood of success while advancing scientific understanding of these diseases and clinical effects of proposed therapies. The DIAN-TU has launched a trial design that leverages the existing infrastructure of the ongoing DIAN observational study, takes advantage of a variety of drug targets, incorporates the latest results of biomarker and cognitive data collected during the observational study, and implements biomarkers measuring Alzheimer's disease (AD) biological processes to improve the efficiency of trial design. The DIAN-TU trial design is unique due to the sophisticated design of multiple drugs, multiple pharmaceutical partners, academics servings as sponsor, geographic distribution of a rare population and intensive safety and biomarker assessments. The implementation of the operational aspects such as home health research delivery, safety magnetic resonance imagings (MRIs) at remote locations, monitoring clinical and cognitive measures, and regulatory management involving multiple pharmaceutical sponsors of the complex DIAN-TU trial are described.

The secretion of progesterone during the periovulatory period in women with certified ovulation.

A pre-LH peak rise of progesterone in peripheral blood has been found in 13 normal cycling women whose ovulation was confirmed by biopsy of the corpus luteum through serial determination of progesterone and LH performed every 8 h during the periovulatory period. The progesterone rise began as an average 22 h (16-40 h) prior to the LH peak. The maximal preovulatory rise took place 9.6 h (0-24 h) before the LH zenith, remaining low for approximately 17 h when an abrupt rise of progesterone took place. The progesterone peak was detected in the morning samples in 11 of 13 patients studied. The progesterone rise was always followed by an LH peak and the highest peak of progesterone was trailed by the highest LH peak in all the patients except one.

Changes in human lymphocyte subpopulations in tonsils and regional lymph nodes of human head and neck squamous carcinoma compared to control lymph nodes.

BACKGROUND: Lymphoid tissues constitute basic structures where specific immune responses take place. This leads to the development of germinal centres (GCs), migration of cells and the generation of memory cells. Here, we have compared human tumour reactive lymph nodes and tonsils with control lymph nodes. RESULTS: The study by flow cytometry shows that in control lymph nodes the majority of cells were naive T-lymphocytes (CD45RA+/CD7+). In reactive nodes, although the percentage of CD45RO+ T cells remains constant, there is an increase in the number of B-lymphocytes, and a reduction in naive T cells. The percentage of cells expressing CD69 was similar in reactive nodes and in controls. In both cases, we have found two populations of B cells of either CD69- or CD69dull. Two populations of T cells, which are either negative for CD69 or express it in bright levels (CD69bright), were also found. The analysis of tissue sections by confocal microscopy revealed differences between control, tonsils and tumor reactive lymph nodes. In control lymph nodes, CD19 B cells are surrounded by a unique layer of CD69bright/CD45RO+ T cells. GCs from tonsils and from tumour reactive nodes are mainly constituted by CD19 B cells and have four distinct layers. The central zone is composed of CD69- B cells surrounded by CD69bright/CD45RO+ T cells. The mantle region has basically CD69dull B-lymphocytes and, finally, there is an outer zone with CD69-/CD45RO+ T cells. CONCLUSIONS: Human secondary lymphoid organs react with an increase in the proportion of B lymphocytes and a decrease in the number of CD45RA+ T cells (naive). In tonsils, this is due to chronic pathogen stimulation, whereas in lymph nodes draining head and neck carcinomas the reaction is prompted by surrounded tumors. During this process, secondary lymphoid organs develop secondary follicles with a special organization of T and B cells in consecutive layers, that are described here by confocal microscopy. This pattern of cellular distribution may suggest a model of cell migration into the secondary lymphoid follicles.

[Fournier's gangrene: computerized tomography findings]. / Gangrena de Fournier: hallazgos en tomografía computerizada.

OBJECTIVE: To describe a case of Fournier's gangrene. The CT findings confirmed the diagnosis and showed the extent of the lesion. METHODS/RESULTS: A young, male alcoholic developed Fournier's gangrene after an episode of urinary tract infection. The extent of the lesion observed on CT correlated with the surgical findings. CONCLUSION: CT evaluation of patients with Fournier's gangrene is advocated. In the case described herein, the extent of the lesion observed on CT correlated with the surgical findings.

Plasma levels of norepinephrine (NE) during the periovulatory period and after LH-RH stimulation in women.

In three normally cycling women studied daily from day 10 to 17 of the menstrual cycle, the levels of circulating norepinephrine showed a sharp rise preceding or concomitantly with the ovulatory LH surge. In two patients the norepinephrine peak took place 24 hr. previously to the LH rise and in the third one it occurred simultaneously. The simultaneous determination of ovarian hormones and norepinephrine showed no temporal correlation between this catecholamine and either estradiol or progesterone. On the other hand, after a single intravenous 100 mug dose of LH-RH, a significant rise in plasma norepinephrine, preceding the LH peak, was found in the four patients studied. The determination of norepinephrine at 3 minute intervals beginning one minute after LH-RH injection showed a significant rise in the amine levels ranging from 5 to 10 times in respect to basal values between 1 and 6 minutes after LH-RH stimulation. In these patients a second peak of norepinephrine occurred simultaneously with the maximal response of LH, which rose to peak levels after 18 minutes in one patient and after 24 minutes in the other. These findings are discussed with respect to the origin and role of increased amounts of plasma norepinephrine related to the LH surge.

Limpieza de las paredes del conducto usando una combinaciónde hipoclorito de sodio 2, 5% - ácido cítrico 10% y clorhexidina 2% - ácido citrico 10% / Clenalness of the root canal walls using a combination of 2, 5% sodium hypoclorte – 10% citric acid and 2% chlorhexidine – 10% citric acid

Objetivo. El propósito de este estudio fue comparar el grado de limpieza de lasparedes del conducto radicular utilizando como irrigantes la combinación de hipoclorito de sodio 2,5% - ácido cítrico 10% y clorhexidina 2% ácitdo cítrico 10%. Material y métodos: Se emplearon raíces de 35 premolares, unirradiculares de conducos rectos recientemente extraídos. L amismas fueron instrumentadas e irigadas con ls soluciones citadas, secciondas longitudinalmente y observadas al MEB a nivel cervial, medio y apical. Resultados: Los resultados indicaron limpieza de las paredes del conducto radicular con el uso de ambas cobinaciones,siendo en e terci medio, estadísticamente más efectiva la obtenida con a asociación hipoclori de sodio 2,5% - ácido cítrico 10% (p= 0,00<0,05). Conclusioes: La asociacion d ehipoclorito de sodio 2,5% - ácido cítirico 10% demostró mayor apacidad para remover la capa residual que la asociación de clorexidina 2%- ácido citrico 10% (AU)

Objective: In this study the cleanliness of the root canal walls was copared, using as irrigators the combinations of 2,5% sodium hypochlorite – 10% citric acid, and 2% chrohexidene – 10% citric acid. Material and methods: 35 single- rooted human premolars, recently extracted wereused. The same roots were instrumented and irigated with the combinatios mentioned above , then roots were sectione and observed with Scanning Electron Microscopic in cervical, middle and apical levels. Reslts: The results showed cleanliness o the root canal walls with the use of both combiations, being statistcaly more significantin the third middle, the one obtained with the combination of 2,5% sodium hypochlorite –10% citric acid (p=0 0<0,05). Conclussions: The association of 2,5% sodium hypochloite 10% citic acid was more efficiente than the combination of 2% chorhexidine- 10% citric acid (AU)