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11.
Milos Chvapil Filip Kielar Frantisek Liska Alexandra Silhankova Klaus Brendel 《Connective tissue research》2013,54(4-5):242-250
This study extends the use of two lathyrogens, β-aminopropionitrile (BAPN) and D-penicillamine (DPA) from daily systemic or local-topical administration to long-time acting agents. This was achieved by converting the hydrophilic drugs into lipophilic derivatives. The synthesis of functional derivatives of DPA consisted in esterification with methyl-, hexyl-, or benzyl alcohols in the presence of thionylchloride. The esters formed were hydrochlorides, acidic and soluble in water. During neutralization in vitro or in vivo by tissue fluid, an oily substance is formed that elutes from a hydrogel polymer at a much slower rate than hydroplilic DPA itself. The degree of lipophilicity, measured as a partition coefficient between octanol/water, was highest for hexyl ester and lowest for methyl ester DPA. A single injection of either DPA hexyl ester HCl or 3-hexyl(amino) propionitrile into the full thickness skin incision wound in rats significantly lowered the breaking strength of the wound 12 days after injection, indicating the interference with collagen cross-linking. Both agents injected into the breast adenocarcinoma in Fisher rats significantly inhibited tumor growth without any signs of local or systemic toxicity. We conclude that these lipophilic lathyrogens with prolonged effectiveness are suitable in the treatment of pathologies, consisting of excessively cross-linked or deposited collagen (fibrotic adhesions, strictures, stenosis, and scar contractures) and in the treatment of single, solitary tumors, malignant and benign. 相似文献
12.
Carla Palleis MD Julia Sauerbeck Leonie Beyer MD Stefanie Harris Julia Schmitt Estrella Morenas-Rodriguez PhD Anika Finze Alexander Nitschmann Francois Ruch-Rubinstein Florian Eckenweber Gloria Biechele Tanja Blume MSc Yuan Shi PhD Endy Weidinger MD Catharina Prix MD Kai Bötzel MD Adrian Danek MD Boris-Stephan Rauchmann MD Sophia Stöcklein MD Simon Lindner PhD Marcus Unterrainer MD Nathalie L. Albert MD Christian Wetzel PhD Rainer Rupprecht MD Axel Rominger MD Peter Bartenstein MD Jochen Herms MD Robert Perneczky MD Christian Haass PhD Johannes Levin MD Günter U. Höglinger MD Matthias Brendel MD 《Movement disorders》2021,36(4):883-894
13.
Carla Palleis MD Matthias Brendel MD Anika Finze Endy Weidinger MD Kai Bötzel MD Adrian Danek MD Leonie Beyer MD Alexander Nitschmann Maike Kern Gloria Biechele Boris-Stephan Rauchmann MD Jan Häckert MD Matthias Höllerhage MD Andrew W. Stephens MD PhD Alexander Drzezga MD Thilo van Eimeren MD Victor L. Villemagne MD Andreas Schildan PhD Henryk Barthel MD Marianne Patt PhD Osama Sabri MD German Imaging Initiative for Tauopathies Peter Bartenstein MD Robert Perneczky MD Christian Haass PhD Johannes Levin MD Günter U. Höglinger MD 《Movement disorders》2021,36(9):2104-2115
14.
15.
[Purpose] The purpose of this study was to investigate the use of smartphones by
university students in selected areas, their musculoskeletal symptoms, and the associated
hazard ratio. [Subjects and Methods] This involved the completion of a self-administered
questionnaire by dental hygiene students in Seoul, Gyeonggido, and Gyeongsangbukdo. The
292 completed copies of the questionnaire were then analyzed. [Results] The most painful
body regions after the use of smartphones were found to be the shoulders and neck. In the
musculoskeletal system, back pain was found to have a positive correlation with the size
of the smartphone’s liquid crystal display (LCD) screen, and pain in legs and feet were
found to have a negative correlation with the length of time that the smartphone was used.
As a result, it was revealed that the use of a smartphone was correlated with
musculoskeletal symptoms. [Conclusion] Therefore, in today’s environment, where the use of
smartphones is on the rise, it is necessary to improve the ways that they are used and to
develop a preventive program to alleviate the symptoms of musculoskeletal damage.Key words: Smartphone, Musculoskeletal symptoms, Prevent 相似文献
16.
DH Mallon M Kostalas FJ MacPherson A Parmar A Drysdale E Chisholm 《Annals of the Royal College of Surgeons of England》2013,95(4):258-262
Introduction
Fine needle aspiration (FNA) is a safe and quick method of diagnosing superficial lumps, which aids preoperative planning. However, FNA of the parotid gland has not gained the widespread acceptance noted in other head and neck lumps. The aim of this study was to determine the ability of FNA of the parotid gland to differentiate benign and malignant disease, and to determine the impact on surgical outcome.Methods
A retrospective analysis of 201 consecutive parotid operations with preoperative FNA in a large district hospital in the UK was performed. The diagnostic characteristics were calculated for benign and malignant disease, and the impact on surgical procedure was determined.Results
In identifying benign disease, FNA has a sensitivity of 85% and a specificity of 76%. In detecting malignant disease, FNA has a sensitivity and specificity of 52% and 92% respectively. A false positive on FNA was associated with a higher incidence of neck dissection.Conclusions
FNA is a useful diagnostic test. However, owing to low sensitivity, it is necessary to interpret it in the context of all other clinical information. 相似文献17.
Koh YW Shah MH Agarwal K McCarty SK Koo BS Brendel VJ Wang C Porter K Jarjoura D Saji M Ringel MD 《Endocrine-related cancer》2012,19(1):29-38
Clinical trials using kinase inhibitors have demonstrated transient partial responses and disease control in patients with progressive medullary thyroid cancer (MTC). The goal of this study was to identify potential combinatorial strategies to improve on these results using sorafenib, a multikinase inhibitor with activity in MTC, as a base compound to explore signaling that might predict synergystic interactions. Two human MTC cell lines, TT and MZ-CRC-1, which harbor endogenous C634W or M918T RET mutations, respectively, were exposed to sorafenib, everolimus, and AZD6244 alone and in combination. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide (MTT) and poly (ADP-ribose) polymerase (PARP) cleavage assays were performed to measure cell survival and apoptosis. Western blots were performed to confirm activity of the compounds and to determine possible mechanisms of resistance and predictors of synergy. As a solitary agent, sorafenib was the most active compound on MTT assay. Western blots confirmed that sorafenib, everolimus, and AZD6244 inhibited their anticipated targets. At concentrations below its IC(50), sorafenib-treated TT and MZ-CRC-1 cells demonstrated transient inhibition and then re-activation of Erk over 6?h. In concordance, synergistic effects were only identified using sorafenib in combination with the Mek inhibitor AZD6244 (P<0.001 for each cell line). Cells treated with everolimus demonstrated activation of Akt and Ret via TORC2 complex-dependent and TORC2 complex-independent mechanisms respectively. Everolimus was neither additive nor syngergistic in combination with sorafenib or AZD6244. In conclusion, sorafenib combined with a Mek inhibitor demonstrated synergy in MTC cells in vitro. Mechanisms of resistance to everolimus in MTC cells likely involved TORC2-dependent and TORC2-independent pathways. 相似文献
18.
Exogenous Lipocalin 2 Ameliorates Acute Rejection in a Mouse Model of Renal Transplantation 下载免费PDF全文
M. I. Ashraf H. G. Schwelberger K. A. Brendel J. Feurle J. Andrassy K. Kotsch H. Regele J. Pratschke F. Aigner 《American journal of transplantation》2016,16(3):808-820
19.
Purpose
Normalised prediction distribution errors (npde) are used to graphically and statistically evaluate mixed-effect models for continuous responses. In this study, our aim was to extend npde to time-to-event (TTE) models and evaluate their performance.Methods
Let V denote a dataset with censored TTE observations. The null hypothesis (H0) is that observations in V can be described by model M. We extended npde to TTE models using imputations to take into account censoring. We then evaluated their performance in terms of type I error and power to detect model misspecifications for TTE data by means of a simulation study with different sample sizes.Results
Type I error was found to be close to the expected 5% significance level for all sample sizes tested. The npde were able to detect misspecifications in the baseline hazard as well as in the link between the longitudinal variable and the survival function. The ability to detect model misspecifications increased as the difference in the shape of the survival function became more apparent. As expected, the power also increased as the sample size increased. Imputing the censored events tended to decrease the percentage of rejections.Conclusions
We have shown that npde can be readily extended to TTE data and that they perform well with an adequate type I error.20.
Gazitt Y; Tian E; Barlogie B; Reading CL; Vesole DH; Jagannath S; Schnell J; Hoffman R; Tricot G 《Blood》1996,87(2):805-811
Peripheral blood stem cells (PBSCs) mobilized with high-dose chemotherapy and hematopoietic growth factors are now widely used to support myeloablative therapy of multiple myeloma and effect complete remissions in up to 50% of patients with apparent extension of event- free and overall survival. Because tumor cells are present not only in bone marrow, but also in virtually all PBSC harvests, it is conceivable that autografted myeloma cells contribute to relapse after autotransplants. In this study, the kinetics of mobilization of normal hematopoietic stem cells were compared with those of myeloma cells present in PBSC harvests of 12 patients after high-dose cyclophosphamide and granulocyte-macrophage colony-stimulating factor administration. CD34+ and CD34+Lin-Thy+ stem cell contents were measured by multiparameter flow cytometry, and myeloma cells were quantitated by immunostaining for the relevant Ig light chain and by a quantitative polymerase chain reaction for the myeloma-specific CDRIII sequence. Results indicated marked heterogeneity in the percentages of mobilized stem cells among different patients (0.1% to 22.2% for CD34+ cells and 0.1% to 7.5% for CD34+Lin-Thy+ cells, respectively). The highest proportions of hematopoietic progenitor cells were observed early during apheresis, with 9 of 12 patients mobilizing adequate amounts of CD34+ cells for 2 autotransplants (> 4 x 10(6)/kg) within the first 2 days, whereas peak levels (percent and absolute numbers) of myeloma cells were present on days 5 and 6 (0.5% to 22.0%). During the last days of collection, mobilized tumor cells exhibited more frequently high labeling index values (1% to 10%; median, 4.4%) and an immature phenotype (CD19+). The differential mobilization observed between normal hematopoietic stem cells and myeloma cells can be exploited to reduce tumor cell contamination in PBSC harvests. 相似文献