排序方式: 共有20条查询结果,搜索用时 0 毫秒
11.
12.
Lee D. Fader Rebekah Carson Sébastien Morin Fran?ois Bilodeau Catherine Chabot Ted Halmos Murray D. Bailey Stephen H. Kawai René Coulombe Steven Laplante Kevork Mekhssian Araz Jakalian Michel Garneau Jianmin Duan Stephen W. Mason Bruno Simoneau Craig Fenwick Youla Tsantrizos Christiane Yoakim 《ACS medicinal chemistry letters》2014,5(6):711-716
13.
Many new interbody fusion cages have been recently developed, but clinical studies analyzing fusion outcome are still scarce. Radiological methods to assess fusion are not standardized and are often unreliable. Cages have been stated to provide good segmental distraction, provide axial load support and reduce segmental mobility, but there have been reports of failed fusions because of implant failure. This paper presents a critical opinion on current cage designs, stressing their clinical and biomechanical implications. Threaded cage designs compromise endplate integrity, and when placed in pairs have inherent limitations for distraction. Non-threaded cage designs usually preserve endplate integrity, but geometry may be inadequate to provide a good surface match to the endplate. The concept of an open frame type cage is believed to have biological advantages, because large graft volumes inside the cage can be in direct contact with host bone. Cadaveric tests suggest that open frame constructs have compressive strength similar to that of full surface contact cages. Restoration of segmental height, sagittal balance and increased neuroforaminal clearance are all functions of disc space distraction. The effect of cage instrumentation on axial load distribution, however, is not well understood. Biomechanical experiments strongly suggest supplementing cage instrumentation with posterior fixation, to achieve a marked increase in initial segmental stability. In the absence of gross segmental instability, micromotion at the host graft interface may still exist. As a result, fusion will never occur, instead a pseudoarthrosis will develop. For monitoring fusion, the use of non-metallic cages has distinct advantages, because no metal artifacts will disturb radiological assessment. 相似文献
14.
目的:探索儿童腹型过敏性紫癜(HSP)的高危因素,为早期诊治提供依据。方法:收集2011年1月至2018年12月在金华市第五医院住院治疗的HSP患儿98例,其中腹型HSP患儿50例,皮肤型HSP患儿48例,比较2组患儿的临床特点和实验室指标。采用logistic回归分析筛选影响儿童腹型HSP的高危因素。结果:腹型HSP患儿出现上呼吸道感染诱因比例显著高于皮肤型HSP患儿,差异均有统计学意义(P<0.05)。腹型HSP患儿的血白细胞计数、中性粒细胞计数、C-反应蛋白、D-二聚体均高于皮肤型HSP患儿,差异有统计学意义(P<0.05);而2组间性别、年龄、发病季节、住院时间以及血红蛋白、血小板计数、血钾、丙氨酸氨基转移酶、天冬氨酸氨基转移酶、血白蛋白、血沉、补体C3、C4、IgA、凝血酶原时间、活化部分促凝血酶原激酶时间差异均无统计学意义(P>0.05)。Logistic回归分析显示上呼吸道感染(OR=3.54,95%CI=1.29~9.75,P=0.014)及D-二聚体增高(OR=4.23,95%CI=1.28~13.96,P=0.018)是儿童腹型HSP发生的独立高危因素。结论:对存在上呼吸道感染以及D-二聚体偏高等高危因素的HSP患儿应予早期干预,积极正确处理,以期防止并发症的发生。 相似文献
15.
Lin YS Park J De Schutter JW Huang XF Berghuis AM Sebag M Tsantrizos YS 《Journal of medicinal chemistry》2012,55(7):3201-3215
Human farnesyl pyrophosphate synthase (hFPPS) controls intracellular levels of FPP and post-translational prenylation of small GTPase proteins, which are essential for cell signaling and cell proliferation. Clinical investigations provide evidence that N-BP inhibitors of hFPPS are disease modifying agents that improve survival of multiple myeloma (MM) patients via mechanisms unrelated to their skeletal effects. A new series of N-BPs was designed that interact with a larger portion of the GPP subpocket, as compared to the current therapeutic drugs, and rigidify the (364)KRRK(367) tail of hFPPS in the closed conformation in the absence of IPP. An analogue of this series was used to demonstrate inhibition of the intended biological target, resulting in apoptosis and down-regulation of ERK phosphorylation in human MM cell lines. 相似文献
16.
Baldé NM Youla A Baldé MD Kaké A Diallo MM Baldé MA Maugendre D 《Diabetes & metabolism》2006,32(2):171-175
AIM: Use of medicinal plants is widespread in Africa, particularly in Guinea where oral transmission of practices is part of the social ritual. The purpose of this study was to determine the proportion of diabetic patients who use herbal medicine and identify the types of plants in use. Reasons for using herbal medicine and the formulations employed were also noted. METHODS: A questionnaire on use of herbal medicine was proposed to all diabetic patients hospitalized or consulting the Endocrinology Unit of the Conakry University Hospital between April 1 and June 30, 2003. RESULTS: A total of 397 patients responded; 33% declared they used herbal medicine. They proposed many motivations, sometimes in association: belief in its efficacy (74%), easy access to medicinal plants (70%), lower cost (48%), and search for complete cure of diabetes (37%). Hearing about a positive experience had convinced 78% of the users to use herbal medicine. The majority of the users were satisfied (85%). One or more clinical manifestations occurring concomitantly with use of herbs was observed in 23 patients (18%), particularly gastrointestinal disorders (n = 10) and skin problems (n = 8). Two cases of hypoglycaemia were noted. CONCLUSION: Herbal medicine plays an important role in anti-diabetes treatment in Guinea. This type of treatment should be based on scientific evidence but very few studies have been conducted. Conditions of use should be better defined and patients should be informed of potential adverse effects. 相似文献
17.
Biomechanical stability of five stand-alone anterior lumbar interbody fusion constructs 总被引:11,自引:0,他引:11
Anterior lumbar interbody fusion (ALIF) cages are expected to reduce segmental mobility. Current ALIF cages have different
designs, suggesting differences in initial stability. The objective of this study was to compare the effect of different stand-alone
ALIF cage constructs and cage-related features on initial segmental stability. Human multi-segmental specimens were tested
intact and with an instrumented L3/4 disc level. Five different ALIF cages (I/F, BAK, TIS, SynCage, and ScrewCage) were tested
non-destructively in axial rotation, flexion/extension and lateral bending. A cage ‘pull-out’ concluded testing. Changes in
neutral zone (NZ) and range of motion (ROM) were analyzed. Cage-related measurements normalized to vertebral dimensions were
used to predict NZ and ROM. No cage construct managed to reduce NZ. The BAK and TIS cages had the largest NZ increase in flexion/extension
and lateral bending, respectively. Cages did reduce ROM in all loading directions. The TIS cage was the least effective in
reducing the ROM in lateral bending. Cages with sharp teeth had higher ‘pull-out’ forces. Antero-posterior and medio-lateral
cage dimensions, cage height and wedge angle were found to influence initial stability. The performance of stand-alone ALIF
cage constructs generally increased the NZ in any loading direction, suggesting potential directions of initial segmental instability that may lead to permanent deformity. Differences between cages in flexion/extension and lateral bending
NZ are attributed to the severity of geometrical cage-endplate surface mismatch. Stand-alone cage constructs reduced ROM effectively,
but the residual ROM present indicates the presence of micromotion at the cage-endplate interface.
Received: 3 June 1999/Revised: 3 September 1999/Accepted: 8 September 1999 相似文献
18.
李尤拉 《临床心身疾病杂志》2012,18(1):15-17
目的 探讨喹硫平联合舍曲林治疗精神分裂症患者伴强迫症状的临床疗效与安全性.方法 将90例精神分裂症伴强迫症状患者随机分为两组,每组45例,两组均口服喹硫平治疗,研究组联合舍曲林治疗,观察8周.于治疗前及治疗第2周、4周、8周末采用阳性与阴性症状量表评定精神症状,Yale Brown强迫症状量表评定强迫症状,副反应量表评定不良反应.结果 治疗后两组阳性与阴性症状量表及Yale Brown强迫症状量表评分均较治疗前显著下降,研究组治疗4周、8周末Yale Brown强迫症状量表总分及强迫思维、强迫行为维度分均较对照组下降更显著(P<0.05或0.01);研究组改善精神症状总有效率达65.91%、改善强迫症状总有效率达86.37%,对照组分别为65.12%、55.81%,研究组改善精神症状总有效率与对照组比较差异无显著性(u=0.02,P>0.05),改善强迫症状总有效率显著高于对照组(u=4.83,P<0.01).两组不良反应均轻微,主要表现为嗜睡、头晕等,发生率差异无显著性(χ2=0.79,P>0.05).结论 喹硫平联合舍曲林治疗精神分裂症患者伴强迫症状疗效显著,不增加不良反应,安全性高,显著优于单用喹硫平治疗. 相似文献
19.
Inhibitors of the HCV NS5B polymerase: new hope for the treatment of hepatitis C infections 总被引:2,自引:0,他引:2
Beaulieu PL Tsantrizos YS 《Current opinion in investigational drugs (London, England : 2000)》2004,5(8):838-850
The spread of hepatitis C virus (HCV) infections and serious health consequences associated with chronic states of the disease have become a global concern. Small-molecule drugs that are specific for anti-HCV chemotherapy are not available and the current treatments for this disease suffer from limited success. The NS5B RNA-dependent RNA polymerase of HCV is an essential enzyme for viral replication. It has emerged in the last years as the most 'drugable' target of the entire HCV genome. While no agents from this class have yet demonstrated sustained efficacy in infected patients, early stage proof-of-concept has been achieved in the clinic, providing validation of the approach for antiviral therapy. This review provides a comprehensive account of the progress made towards the discovery of anti-HCV therapeutics based on inhibition of the virally encoded NS5B polymerase. 相似文献
20.
PL Beaulieu M Bös MG Cordingley C Chabot G Fazal M Garneau JR Gillard E Jolicoeur S Laplante G McKercher M Poirier MA Poupart YS Tsantrizos J Duan G Kukolj 《Journal of medicinal chemistry》2012,55(17):7650-7666
Combinations of direct acting antivirals (DAAs) that have the potential to suppress emergence of resistant virus and that can be used in interferon-sparing regimens represent a preferred option for the treatment of chronic HCV infection. We have discovered allosteric (thumb pocket 1) non-nucleoside inhibitors of HCV NS5B polymerase that inhibit replication in replicon systems. Herein, we report the late-stage optimization of indole-based inhibitors, which began with the identification of a metabolic liability common to many previously reported inhibitors in this series. By use of parallel synthesis techniques, a sparse matrix of inhibitors was generated that provided a collection of inhibitors satisfying potency criteria and displaying improved in vitro ADME profiles. "Cassette" screening for oral absorption in rat provided a short list of potential development candidates. Further evaluation led to the discovery of the first thumb pocket 1 NS5B inhibitor (BILB 1941) that demonstrated antiviral activity in patients chronically infected with genotype 1 HCV. 相似文献