To determine histomorphometric and bone strength distribution of the proximal humerus, analyses were done on 24 freshly harvested human cadaveric humeri. Median ages of 46 and 69 years were recorded respectively for the male group (n = 11; minimum, 34 years; maximum, 76 years) and the female group (n = 13; minimum, 46 years; maximum, 90 years). The humeral head was sliced into four equal horizontal levels (Levels 1-4). Five regions of interest were defined in each cutting plane: anterior, posterior, lateral, medial, and central. Histomorphometric analyses evaluated structural parameters (tissue volume to bone volume ratio, trabecular thickness), connectivity (number of nodes, node to node length), and trabecular orientation (mean bone length). The peak values of histomorphometric parameters and bone strength were identified for the cranial section and decreased caudally. The medial and dorsal aspects of the proximal humeral head were found to be the areas of highest bone strength. The trabecular network formed a pattern that connected the center of the gleaned cavity. The structural and connectivity parameters, bone strength, and trabecular orientation showed region- and level-related characteristics. Knowledge of distribution, microstructure, and quality of bone in the humeral head allows the remaining bone stock to be used effectively, even in elderly patients, with a minimally invasive approach and maximum mechanical stability.
Perilesional changes of chronic focal osteochondral defects were assessed in the knees of 23 sheep. An osteochondral defect was created in the main load-bearing region of the medial condyle of the knees in a controlled, standardised manner. The perilesional cartilage was evaluated macroscopically and biopsies were taken at the time of production of the defect (T0), during a second operation one month later (T1), and after killing animals at three (T3; n = 8), four (T4; n = 8), and seven (T7; n = 8) months. All the samples were histologically assessed by the International Cartilage Repair Society grading system and Mankin histological scores. Biopsies were taken from human patients (n = 10) with chronic articular cartilage lesions and compared with the ovine specimens. The ovine perilesional cartilage presented with macroscopic and histological signs of degeneration. At T1 the International Cartilage Repair Society 'Subchondral Bone' score decreased from a mean of 3.0 (SD 0) to a mean of 1.9 (SD 0.3) and the 'Matrix' score from a mean of 3.0 (SD 0) to a mean of 2.5 (SD 0.5). This progressed further at T3, with the International Cartilage Repair Society 'Surface' grading, the 'Matrix' grading, 'Cell Distribution' and 'Cell Viability' grading further decreasing and the Mankin score rising from a mean of 1.3 (SD 1.4) to a mean of 5.1 (SD 1.6). Human biopsies achieved Mankin grading of a mean of 4.2 (SD 1.6) and were comparable with the ovine histology at T1 and T3. The perilesional cartilage in the animal model became chronic at one month and its histological appearance may be considered comparable with that seen in human osteochondral defects after trauma.
Our findings suggest that NVP-LBH589 and NVP-LAQ824 are active against human pancreatic cancer, although the precise mechanism of in vivo drug action is not yet completely understood. Therefore, further preclinical and clinical studies for the treatment of pancreatic cancer are recommended.
Tumor components with contrast-enhancing non-fatty, non-myxoid imaging features were predominantly found in high-grade myxoid liposarcomas, which may histologically resemble round cell clusters.
Our findings suggest that NVP-LBH589 and NVP-LAQ824 are active against human biliary tract cancer in vitro. In addition, NVP-LBH589 demonstrated significant in vivo activity and potentiated the efficacy of gemcitabine. Therefore, further clinical evaluation of this new drug for the treatment of biliary tract cancer is recommended.
Achondrogenesis type IA (Houston-Harris) is an extremely rare lethal chondrodysplasia with a characteristic severe disarrangement of endochondral ossification. The growth plate cartilage completely lacks columnar-zone formation and shows chondrocyte expansion due to intracellular vacuoles. This article on a new case of achondrogenesis type IA confirms these findings and demonstrates, on the ultrastructural level, the retention of fine fibrillar material within the rough endoplasmic reticulum (rER). Molecular analysis in the presented case of achondrogenesis type IA did not reveal mutations in the COL2A1 and SLC26A2 genes, which are known to cause achondrogenesis types IB and type II. Although the extracellular cartilage matrix was severely altered, all of the investigated matrix molecules (collagens, aggrecan, matrilins, cartilage oligomeric protein [COMP]) showed a normal distribution pattern. The only exception was type-X collagen, which was significantly reduced. Overall, our study suggests a disturbance in cartilage matrix assembly in the present case due to the retention of some sort of matrix component within the rER. Presumably, as a consequence of this event, processes of chondrocyte maturation and differentiation and endochondral bone formation are severely affected in this case of achondrogenesis type IA.
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