Analytical and Functional Determination of Polymyxin B Protein Binding in Serum

To enhance our understanding of the pharmacological properties of polymyxin B, serum protein binding for polymyxin B1, B2, and B3 and for isoleucine-polymyxin B1 was evaluated. Using equilibrium dialysis and ultrafiltration, comparable protein binding was found in all 4 components of polymyxin B (92% to 99%). Protein binding in human serum was further assessed using a functional assay, the results of which were in general agreement with previous findings (approximately 90%).     

Die Olekranonosteotomie

In recent years the increase of interest for surgery of the elbow has fostered the development of new and modified triceps sparing approaches. Olecranon osteotomy is a widely accepted method especially for open reduction and internal fixation of displaced intra-articular fractures because it provides excellent exposure of the joint surfaces. Due to several reports describing numerous complications, the enthusiasm for this procedure is currently limited. Several intra-articular and extra-articular techniques for refixation of the olecranon have been developed to limit these complications and good results have been obtained. This paper describes various techniques, analyzes advantages and disadvantages and shows alternative ways and solutions for different indications.     

Vitiligo in children and adolescents: association with thyroid dysfunction

Background The clinical characteristics of vitiligo in children and adolescents with an emphasis on thyroid dysfunction have only been reported in a few studies. Objective The purpose of this study was to examine the characteristics of children and adolescents with vitiligo and compare the incidence of thyroid dysfunction between them and controls without vitiligo at the same age. Methods A retrospective analysis of 324 Korean children and adolescents with vitiligo was performed. The results of thyroid function screening tests in them (n = 254) were compared with controls (n = 122). Results Of the total 324 children and adolescents with vitiligo, vitiligo vulgaris was the most common type (42.3%) and the most commonly involved site was the face (54.6%). A total of 15 of 254 (5.9%) patients screened for thyroid function were diagnosed with thyroid disease (four had Hashimoto’s thyroiditis; two, Graves’ disease; seven, subclinical hypothyroidism; and two, subclinical hyperthyroidism). None of the 50 patients with segmental vitiligo showed any thyroid dysfunction (P = 0.047). There was no significant difference in the incidence of thyroid disease between children and adolescents with vitiligo and the control group, in which seven of 122 (5.7%) showed thyroid dysfunction. Conclusion In this study, we demonstrated the characteristics of children and adolescents with vitiligo and also observed no significant difference in the incidence of thyroid disease between children and adolescents with vitiligo and the control group.     

美国教学医院教师专业发展的全国性调查

在当前医学教育持续变革的背景中,医学教师的专业发展成为广泛关注的焦点.为了解目前美国以提高教师的教学技能为目标的教师专业发展(faculty development,FD)活动的参与率、课程设计、教学方法和评估策略等情况,美国约翰·霍普金斯大学预防、流行病学和临床研究中心采取邮件调查的方式,对美国277家教学医院进行了调查.     

Synthesis of diagnostic quality cancer pathology images by generative adversarial networks

Deep learning-based computer vision methods have recently made remarkable breakthroughs in the analysis and classification of cancer pathology images. However, there has been relatively little investigation of the utility of deep neural networks to synthesize medical images. In this study, we evaluated the efficacy of generative adversarial networks to synthesize high-resolution pathology images of 10 histological types of cancer, including five cancer types from The Cancer Genome Atlas and the five major histological subtypes of ovarian carcinoma. The quality of these images was assessed using a comprehensive survey of board-certified pathologists (n = 9) and pathology trainees (n = 6). Our results show that the real and synthetic images are classified by histotype with comparable accuracies and the synthetic images are visually indistinguishable from real images. Furthermore, we trained deep convolutional neural networks to diagnose the different cancer types and determined that the synthetic images perform as well as additional real images when used to supplement a small training set. These findings have important applications in proficiency testing of medical practitioners and quality assurance in clinical laboratories. Furthermore, training of computer-aided diagnostic systems can benefit from synthetic images where labeled datasets are limited (e.g. rare cancers). We have created a publicly available website where clinicians and researchers can attempt questions from the image survey ( http://gan.aimlab.ca/ ). © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Multiple tumor-suppressor gene 1 inactivation is the most frequent genetic alteration in T-cell acute lymphoblastic leukemia

No constant genetic alteration has yet been unravelled in T-cell acute lymphoblastic leukemia (T-ALL), and, to date, the most frequent alteration, the SIL-TAL1 deletion, is found in approximately 20% of cases. Recently, two genes have been identified, the multiple tumor- suppressor gene 1 (MTS1) and multiple tumor-suppressor gene 2 (MTS2), whose products inhibit cell cycle progression. A characterization of the MTS locus organization allowed to determine the incidence of MTS1 and MTS2 inactivation in T-ALL. MTS1 and MTS2 configurations were determined by Southern blotting using 8 probes in 59 patients with T- ALL (40 children and 19 adults). Biallelic MTS1 inactivation by deletions and/or rearrangements was observed in 45 cases (76%). Monoallelic alterations were found in 6 cases (10%). The second MTS1 allele was studied in the 4 cases with available material. A point mutation was found in 2 cases. The lack of MTS1 mRNA expression was observed by Northern blot analysis in a third case. A normal single- strand conformation polymorphism pattern of MTS1 exons 1alpha and 2 was found and MTS1 RNA was detected in the fourth case, but a rearrangement occurring 5' to MTS1 exon 1 alpha deleting MTS1 exon 1Beta was documented. One case presented a complex rearrangement. Germline configuration for MTS1 and MTS2 was found in only 7 cases. The localization of the 17 breakpoints occurring in the MTS locus were determined. Ten of them (59%) are clustered in a 6-kb region located 5 kb downstream to the newly identified MTS1 exon 1Beta. No rearrangement disrupting MTS2 was detected and more rearrangements spared MTS2 than MTS1 (P<.01). MTS1 but not MTS2 RNA was detected by Northern blotting in the human thymus. These data strongly suggest that MTS1 is the functional target of rearrangements in T-ALL. MTS1 inactivation, observed in at least 80% of T-ALL, is the most consistent genetic defect found in this disease to date.     

Some properties of marrow derived adherent cells in tissue culture

It has previously been shown that monolayer cultures derived adherent cells (MDAC), apparently consisting of fibroblasts, macrophages, epithelioid cells, and fat cells, can support long-term stem cell proliferation in vitro. In the present study, the hematopoietic support capability of murine MDAC monolayers was confirmed and the cultured cells further characterized with respect to the following properties: esterase I activity, complement (C3) receptors, IgG (Fc) receptors, colony stimulating activity (csa) production, and collagen synthesis. The cultures were also examined immunohistochemically to localize fibronectin, laminin, and collagen synthesis and to identify the collagen subtypes synthesized. MDAC morphology was as described in previous studies, although fat cells were few in number. It was found that MDAC included some cells with esterase I activity and C3 receptors. Fc receptors were not, however, detected, nor did the cultures produce csa, indicating that mononuclear phagocytes were not present. MDAC synthesized collagen types I and III and also fibronectin. Staining for epithelial basement membrane proteins (collagen types IV and V and laminin) was negative. The results indicate that the vast majority of these cultured MDAC were fibroblasts.