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101.
Nagui S. T. Gendi Ken I. Welsh Walther J. Van Venrooij Rama Vancheeswaran Jill Gilroy Carol M. Black 《Arthritis \u0026amp; Rheumatology》1995,38(2):259-266
Objective. To determine any clinical or genetic markers of differentiation and outcome in a previously described cohort of 46 patients with mixed connective tissue disease (MCTD). Methods. Patients were clinically evaluated, chart notes reviewed, and HLA subtyping and immunology profiles performed where possible. Eleven had died and 7 were lost to followup. Results. MCTD had differentiated into systemic lupus erythematosus in 12 patients and into systemic sclerosis in 13. The latter was associated with HLA-DR5 (P = 0.038), and nondifferentiation was associated with HLA-DR2 or DR4 (P = 0.007). Three HLA-DR4 positive patients had MCTD that evolved into rheumatoid arthritis. Erosive and/or deforming arthritis was associated with HLA-DR1 or DR4 (P = 0.015). HLA-DR3 was associated with interstitial lung fibrosis (P = 0.044) and keratoconjunctivitis sicca (0.001 < P < 0.01). Severe Raynaud's phenomenon predicted higher mortality (0.01 < P < 0.05). Conclusion. We suggest that MCTD is, for most patients, an intermediate stage in a genetically determined progression to a recognized connective tissue disease. Those whose disease remains undifferentiated might be considered a distinct subset. 相似文献
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Helen Mossop Michael J. Grayling Ferdia A. Gallagher Sarah J. Welsh Grant D. Stewart James M. S. Wason 《British journal of cancer》2022,126(2):204
Background Efficient trial designs are required to prioritise promising drugs within Phase II trials. Adaptive designs are examples of such designs, but their efficiency is reduced if there is a delay in assessing patient responses to treatment.Methods Motivated by the WIRE trial in renal cell carcinoma (), we compare three trial approaches to testing multiple treatment arms: (1) single-arm trials in sequence with interim analyses; (2) a parallel multi-arm multi-stage trial and (3) the design used in WIRE, which we call the Multi-Arm Sequential Trial with Efficient Recruitment (MASTER) design. The MASTER design recruits patients to one arm at a time, pausing recruitment to an arm when it has recruited the required number for an interim analysis. We conduct a simulation study to compare how long the three different trial designs take to evaluate a number of new treatment arms.Results The parallel multi-arm multi-stage and the MASTER design are much more efficient than separate trials. The MASTER design provides extra efficiency when there is endpoint delay, or recruitment is very quick.Conclusions We recommend the MASTER design as an efficient way of testing multiple promising cancer treatments in non-comparative Phase II trials.Subject terms: NCT03741426Adaptive clinical trial, Randomized controlled trials 相似文献
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Repeatability and sensitivity of
measurements in patients with head and neck squamous cell carcinoma at 3T
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Rafal Panek PhD Liam Welsh PhD Alex Dunlop PhD Kee H. Wong MSc Angela M. Riddell MD Dow‐Mu Koh MD Maria A. Schmidt PhD Simon Doran PhD Dualta Mcquaid PhD Georgina Hopkinson PgDip Cheryl Richardson DCR Christopher M. Nutting PhD Shreerang A. Bhide PhD Kevin J. Harrington PhD Simon P. Robinson PhD Kate L. Newbold MD Martin O. Leach PhD 《Journal of magnetic resonance imaging : JMRI》2016,44(1):72-80
107.
Increased accuracy of renal allograft rejection diagnosis using combined perforin, granzyme B, and Fas ligand fine-needle aspiration immunocytology 总被引:10,自引:0,他引:10
BACKGROUND: Two major routes by which cytotoxic T lymphocytes induce apoptosis in target cells are the perforin-granzyme and the Fas ligand/Fas pathways. Intragraft expression of message for these immune activation genes has been shown to correlate very closely with clinical rejection. We have immunolabeled fine-needle aspiration biopsy samples using a panel of cytotoxic T-cell activation markers to evaluate the immunocytochemical identification of the protein products of these genes in the verification of human renal allograft rejection. METHODS: In this retrospective pilot study, 140 fine-needle aspiration biopsy samples from 50 human renal allografts were labeled using alkaline phosphatase/ anti-alkaline phosphatase immunocytochemistry incorporating monoclonal antibodies to perforin, granzyme B, and Fas ligand. Levels of positive labeling for these markers were compared with the original clinical diagnosis of rejection. RESULTS: An excellent correlation with clinical rejection was obtained when all three antibodies were positive. The false positive rate for each antibody was sufficient to make any one alone or in combination with one other unreliable for diagnosing rejection. When all three antibodies gave positive labeling, agreement with clinical rejection status was superior to using conventional morphological cytology. CONCLUSIONS: In addition to providing valuable morphological information regarding the composition of inflammatory leukocyte populations and the preservation status of renal parenchymal cells, fine-needle aspiration biopsy samples may be labeled using combined perforin, granzyme B, and Fas ligand immunocytochemistry to offer a safe and reliable method for diagnosing rejection with an excellent level of accuracy. 相似文献
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