Comparative investigation of the fetus and adult joint ligament in the knee and elbow with structural levels / Investigación comparativa del ligamento conjunto de rodilla y codo con niveles estructurales en fetos y adultos

The aim of this study was to examine and compare fetal and adult knee and elbow joint ligaments and determine histologically how these ligaments change over time. In addition, the images of fetal and adult joint ligaments were examined with magnetic resonance imaging (MRI). This study was conducted on 10 male fetus ranging from ages 14 to 17.5 weeks, two adult male cadavers obtained from Gazi University Faculty of Medicine Department of Anatomy and MR images of the knee and elbow regions of 10 male adults obtained from Atatürk Educational and Research Hospital between 2009 and 2011. In the present study, the sections taken from knee and elbow of ten 14­17.5 week old fetuses and the ligaments of tissue taken from the knee and elbow of two male cadavers using the same method of dissection were monitored. After monitoring tissue, microtome sections taken from paraffin-embedded structures were stained using the Masson-Trichrom and Orcein-Picroindigocarmine staining method. These sections were examined under a microscope and photographed. The images of 17 week old fetuses and the knee and elbow of the adults were obtained with MRI. The differences detected between adult and fetus ligaments consisted of fibroblast density and collagen thickness, density and waves. Although the fetus ligaments were not seen sufficiently with 1.5 Tesla (T) MR, they were seen very clearly with 3 T MR. Structural differences between adult and fetal ligaments revealed in histological and MRI images.

El objetivo del estudio fue examinar y comparar los ligamentos de la articulación de la rodilla y del codo en fetos y adultos y determinar histológicamente como estos ligamentos cambian con el tiempo. Además, las imágenes de los ligamentos de las articulaciones fetales y adultas se examinaron con imágenes de resonancia magnética (IRM). Fueron utilizados 10 fetos masculinos entre 14 y 17,5 semanas, y dos cadáveres adultos masculinos obtenidos del Departamento de Anatomía, Facultad de Medicina de la Universidad Gazi junto con las IRM de las regiones de la rodilla y del codo de 10 hombres adultos obtenidos de Atatürk Educativa y del Hospital de Investigación entre los años 2009 y 2011. Para las secciones de rodilla y codo de los diez fetos y de los cadáveres masculinos se utilizó el mismo método de disección. Después de procesar los tejidos e incluirlos en parafina, se obtuvieron cortes en micrótomo los cuales fueron posteriormente teñidos con Tricrómico de Masson y Orceína-picro-índigo Carmín. Las secciones fueron fotografiadas y examinadas bajo microscopio. Se obtuvieron IRM del codo y de la rodilla de los fetos y adultos. Las diferencias encontradas entre los ligamentos de adultos y fetos estaban en relación a la densidad de fibroblastos y espesor de colágeno. Aunque no fue posible observar los ligamentos fetales con 1,5 Tesla (T) MR, se observaron claramente con 3 T MR. Las diferencias estructurales entre los ligamentos fetales y adultos se observan tanto a nivel histológico y de resonancia magnética.

Phase II, double-blind, randomized trial of capecitabine plus enzastaurin versus capecitabine plus placebo in patients with metastatic or recurrent breast cancer after prior anthracycline and taxane therapy.

Capecitabine is frequently used in the treatment of recurrent/progressive metastatic breast cancer (MBC) after prior anthracycline and taxane therapy. With the intention of improving the efficacy of single agent capecitabine, we initiated a randomized, double-blind, placebo-controlled Phase II study of the novel serine/threonine kinase inhibitor enzastaurin in combination with capecitabine in a heavily pretreated patient population. Patients received capecitabine 1,250 mg/m(2) twice daily plus enzastaurin 500 mg/day, or capecitabine plus placebo. The capecitabine was administered for the first 14 days of each 21 day cycle. The primary outcome was progression-free survival (PFS) using the log-rank test (1-sided significance level of 0.20). Of 109 patients assessed for eligibility, 85 were enrolled, randomized, and treated (42 and 43 patients in each respective treatment group). The study was terminated early following a preplanned futility analysis. Median PFS (95% CI) was 2.8 (2.1-4.6) months with capecitabine plus enzastaurin versus 4.3 (2.9-6.2) months with capecitabine plus placebo (adjusted hazard ratio: 1.728 [1.00-2.97]; P = 0.048). Median overall survival (95% CI) was lower with capecitabine plus enzastaurin than with capecitabine plus placebo (9.9 [7.0-16.6] months vs 14.9 [9.9-19.3] months, P = 0.181). Grade 3/4 adverse events were more frequent with capecitabine plus enzastaurin (42.9% vs 32.6%). Given the lack of PFS benefit, capecitabine plus enzastaurin is unsuitable as therapy for patients with recurrent/progressive MBC after prior anthracycline and taxane therapy. This trial is registered on www.clinicaltrials.gov (identifier: NCT00437294).

Segmentation of blood vessels from red-free and fluorescein retinal images.

The morphology of the retinal blood vessels can be an important indicator for diseases like diabetes, hypertension and retinopathy of prematurity (ROP). Thus, the measurement of changes in morphology of arterioles and venules can be of diagnostic value. Here we present a method to automatically segment retinal blood vessels based upon multiscale feature extraction. This method overcomes the problem of variations in contrast inherent in these images by using the first and second spatial derivatives of the intensity image that gives information about vessel topology. This approach also enables the detection of blood vessels of different widths, lengths and orientations. The local maxima over scales of the magnitude of the gradient and the maximum principal curvature of the Hessian tensor are used in a multiple pass region growing procedure. The growth progressively segments the blood vessels using feature information together with spatial information. The algorithm is tested on red-free and fluorescein retinal images, taken from two local and two public databases. Comparison with first public database yields values of 75.05% true positive rate (TPR) and 4.38% false positive rate (FPR). Second database values are of 72.46% TPR and 3.45% FPR. Our results on both public databases were comparable in performance with other authors. However, we conclude that these values are not sensitive enough so as to evaluate the performance of vessel geometry detection. Therefore we propose a new approach that uses measurements of vessel diameters and branching angles as a validation criterion to compare our segmented images with those hand segmented from public databases. Comparisons made between both hand segmented images from public databases showed a large inter-subject variability on geometric values. A last evaluation was made comparing vessel geometric values obtained from our segmented images between red-free and fluorescein paired images with the latter as the "ground truth". Our results demonstrated that borders found by our method are less biased and follow more consistently the border of the vessel and therefore they yield more confident geometric values.