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91.
The molecular basis of type I or III Protein S deficiency has been investigated in three kindred also showing independent inheritance of factor V (FV) Leiden. A T to C transition in codon 570 (Met-->Thr) was identified in the propositi and shown to segregate with protein S deficiency in all but one of the affected members of two kindred. This individual was heterozygous for a second transition (C to T) causing substitution of serine 624 by leucine. A second member of the same family, with markedly reduced free protein S levels when compared with affected relatives, was heterozygous for both mutations. Haplotype analysis of individuals with the mutated ATG570ACG allele in the two kindred suggested they may have been related by a common ancestor. A G to A transition resulting in substitution of cysteine 145 by tyrosine was detected in the third kindred. All mutations are believed to interfere with protein S binding to C4b-binding protein resulting in reduced free protein S levels. Of the five individuals studied who had experienced thrombotic events, three had combined protein S deficiency and FV Leiden reemphasising the importance of FV Leiden as an additional risk factor for thrombosis in protein S deficiency. 相似文献
92.
Exploring doctor and patient views about risk communication and shared decision-making in the consultation 总被引:2,自引:1,他引:1
Ruth E Davis MPhil BN RGN NDNCert PGCE Gina Dolan BSc MSc Sue Thomas MSc RGN PGCE RNT PNCert Christine Atwell BA PGDRM PGDCG Cert.Ed PGCE FE † Donna Mead PhD MSc DANS Dip N RGN RCNT RNT Sarah Nehammer BSc Laurie Moseley MA Dip Soc Ad MBCS Adrian Edwards MRCP MRCGP ‡ Glyn Elwyn BA FRCGP PhD ‡ 《Health expectations》2003,6(3):198-207
Background There have been significant conceptual developments regarding shared decision‐making (SDM) and assessments of people's hypothetical preferences for involvement in treatment or care decisions. There are few data on the perceptions of patients and professionals about SDM in actual practice. Objective To explore, from paired doctor–patient interviews, participants’ perceptions of SDM in the consultation and the level of consensus between the participants in the consultation process. Design Qualitative analysis of semi‐structured interview data. Setting and participants Twenty general practitioners received training packages in ‘risk communication’ (RC) and ‘SDM’ to use as tools within the consultation. Forty patients with one of four conditions, for which a range of treatment options is available, were selected. Patient/doctor pairs were interviewed separately following consultations at four stages –‘baseline’ [general practitioner's (GP) usual consultation style], SDM training, RC alone, and both RC and SDM training. Interviews were transcribed and analysed using NVivo software. Results Risk communication interventions by doctors appeared to result in a greater perception of decisions being made in the consultation. High levels of satisfaction with consultations were evident before application of the interventions and did not change after the interventions. Doctors’ and patients’ perceptions of the consultations were highly congruent at all phases of the study. Conclusion Shared decision‐making and RC approaches were helpful in selected consultations and showed no detrimental effects to patients. However, the use of RC and SDM made only small differences to decision‐making in consultations within the population studied. Increasing patient participation may be seen as more ethically justifiable than the traditional paternalistic approach but this needs to be set against the additional training costs incurred. 相似文献
93.
Hemalatha G. Rangarajan Rowena C. Punzalan Bruce M. Camitta Julie‐An M. Talano 《British journal of haematology》2013,163(3):357-364
Interleukin‐6 (IL6) plays a central role in multiple myeloma pathogenesis and confers resistance to corticosteroid‐induced apoptosis. We therefore evaluated the efficacy and safety of siltuximab, an anti‐IL6 monoclonal antibody, alone and in combination with dexamethasone, for patients with relapsed or refractory multiple myeloma who had ≥2 prior lines of therapy, one of which had to be bortezomib‐based. Fourteen initial patients received siltuximab alone, 10 of whom had dexamethasone added for suboptimal response; 39 subsequent patients were treated with concurrent siltuximab and dexamethasone. Patients received a median of four prior lines of therapy, 83% were relapsed and refractory, and 70% refractory to their last dexamethasone‐containing regimen. Suppression of serum C‐reactive protein levels, a surrogate marker of IL6 inhibition, was demonstrated. There were no responses to siltuximab but combination therapy yielded a partial (17%) + minimal (6%) response rate of 23%, with responses seen in dexamethasone‐refractory disease. The median time to progression, progression‐free survival and overall survival for combination therapy was 4·4, 3·7 and 20·4 months respectively. Haematological toxicity was common but manageable. Infections occurred in 57% of combination‐treated patients, including ≥grade 3 infections in 18%. Further study of siltuximab in modern corticosteroid‐containing myeloma regimens is warranted, with special attention to infection‐related toxicity. 相似文献
94.
Domenico Scrutinio Enrico Ammirati Pietro Guida Andrea Passantino Rosa Raimondo Valentina Guida Simona Sarzi Braga Roberto FE Pedretti Rocco Lagioia Maria Frigerio Raffaella Catanzaro Fabrizio Oliva 《International journal of cardiology》2013
Background
NT-proBNP has been associated with prognosis in acute decompensated heart failure (ADHF). Whether NT-proBNP provides additional prognostic information beyond that obtained from standard clinical variables is uncertain. We sought to assess whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) determination improves risk reclassification of patients with ADHF and to develop and validate a point-based NT-proBNP risk score.Methods
This study included 824 patients with ADHF (453 in the derivation cohort, 371 in the validation cohort). We compared two multivariable models predicting 1-year all-cause mortality, including clinical variables and clinical variables plus NT-proBNP. We calculated the net reclassification improvement (NRI) and the integrated discrimination improvement (IDI). Then, we developed and externally validated the NT-proBNP risk score.Results
One-year mortalities for the derivation and validation cohorts were 28.3% and 23.4%, respectively. Multivariable predictors of mortality included chronic obstructive pulmonary disease, estimated glomerular filtration rate, sodium, hemoglobin, left ventricular ejection fraction, and moderate to severe tricuspid regurgitation. Adding NT-proBNP to the clinical variables only model significantly improved the NRI (0.129; p = 0.0027) and the IDI (0.037; p = 0.0005). In the derivation cohort, the NT-proBNP risk score had a C index of 0.839 (95% CI: 0.798–0.880) and the Hosmer–Lemeshow statistic was 1.23 (p = 0.542), indicating good calibration. In the validation cohort, the risk score had a C index of 0.768 (95% CI: 0.711–0.817); the Hosmer–Lemeshow statistic was 2.76 (p = 0.251), after recalibration.Conclusions
The NT-proBNP risk score provides clinicians with a contemporary, accurate, easy-to-use, and validated predictive tool. Further validation in other datasets is advisable. 相似文献95.
Sarah M. Cheal Blesida Punzalan Michael G. Doran Michael J. Evans Joseph R. Osborne Jason S. Lewis Pat Zanzonico Steven M. Larson 《European journal of nuclear medicine and molecular imaging》2014,41(5):985-994
Purpose
The PET tracer, 124I-cG250, directed against carbonic anhydrase IX (CAIX) shows promise for presurgical diagnosis of clear-cell renal cell carcinoma (ccRCC) (Divgi et al. in Lancet Oncol 8:304–310, 2007; Divgi et al. in J Clin Oncol 31:187–194, 2013). The radiometal 89Zr, however, may offer advantages as a surrogate PET nuclide over 124I in terms of greater tumor uptake and retention (Rice et al. in Semin Nucl Med 41:265–282, 2011). We have developed a nonlinear immunokinetic model to facilitate a quantitative comparison of absolute uptake and antibody turnover between 124I-cG250 and 89Zr-cG250 using a human ccRCC xenograft tumor model in mice. We believe that this unique model better relates quantitative imaging data to the salient biological features of tumor antibody–antigen binding and turnover.Methods
We conducted experiments with 89Zr-cG250 and 124I-cG250 using a human ccRCC cell line (SK-RC-38) to characterize the binding affinity and internalization kinetics of the two tracers in vitro. Serial PET imaging was performed in mice bearing subcutaneous ccRCC tumors to simultaneously detect and quantify time-dependent tumor uptake in vivo. Using the known specific activities of the two tracers, the equilibrium rates of antibody internalization and turnover in the tumors were derived from the PET images using nonlinear compartmental modeling.Results
The two tracers demonstrated virtually identical tumor cell binding and internalization but showed markedly different retentions in vitro. Superior PET images were obtained using 89Zr-cG250, owing to the more prolonged trapping of the radiolabel in the tumor and simultaneous washout from normal tissues. Estimates of cG250/CAIX complex turnover were 1.35 – 5.51?×?1012 molecules per hour per gram of tumor (20 % of receptors internalized per hour), and the ratio of 124I/89Zr atoms released per unit time by tumor was 17.5.Conclusion
Pairwise evaluation of 89Zr-cG250 and 124I-cG250 provided the basis for a nonlinear immunokinetic model which yielded quantitative information about the binding and internalization of radioantibody bound to CAIX on tumor cells in vivo. 89Zr-cG250 is likely to provide high-quality PET images and may be a useful tool to quantify CAIX/cG250 receptor turnover and cG250-accessible antigen density noninvasively in humans. 相似文献96.
97.
严重多发伤的早期救治 总被引:19,自引:5,他引:14
目的 探讨严重多发伤的早期救治方法。方法 总结1990年1月-2003年12月救治的严重多发伤2358例临床资料(其中2145例接受了ICU监护和治疗),分析严重多发伤早期救治中的几个重要问题,并提出救治工作的要点。结果 本组早期诊断正确率95.04%(2 241/2 358)。发生ARDS 228例(9.67%),MODS 236例(10%),应激性溃疡伴出血103例(4.37%)。ARDS治愈率69.30%(158/228);MODS治愈率53.81%(127/236);应激性溃疡治愈率74.75%(77/103)。全组总治愈率89.86%(2 119/2 358),死亡率10.14%(239/2 358)。结论 提高早期诊断率、合理应用损伤控制外科技术、及时修复及动脉栓塞治疗腹膜后血管损伤等措施对提高严重多发伤的救治成功率至关重要。 相似文献
98.
99.
Low-dose fibrinolytic therapy. Results and new concepts 总被引:2,自引:0,他引:2
Becker GJ; Rabe FE; Richmond BD; Holden RW; Yune HY; Dilley RS; Bang NU; Glover JL; Klatte EC 《Radiology》1983,148(3):663
100.