Identification of polymorphisms in the 3′-untranslated region of the human pregnane X receptor (PXR) gene associated with variability in cytochrome P450 3A (CYP3A) metabolism

1. Single nucleotide polymorphisms in the 3′-untranslated region (3′UTR) of the human pregnane X receptor (PXR) gene might contribute to interindividual variability in cytochrome P450 3A (CYP3A) activity.

2. Genotype–phenotype associations involving PXR-3′UTR single nucleotide polymorphisms were investigated through in vitro (53 human livers from primarily White donors) and in vivo (26 mainly White or African-American volunteers) studies using midazolam 1′-hydroxylation and midazolam apparent oral clearance (CL/F), respectively, as CYP3A-specific probes.

3. PXR-3′UTR resequencing identified twelve single nucleotide polymorphisms, including two that were novel. Although none of the single nucleotide polymorphisms evaluated were associated with altered midazolam 1′-hydroxylation in the liver bank, both rs3732359 homozygotes and rs3732360 carriers showed 80% higher (p?<?0.05) CL/F compared with homozygous reference individuals. These differences in CL/F were even larger (100% and 120% higher, respectively; p?<?0.01) when only African-American subjects (n = 14) were considered.

4. Five major haplotypes were identified containing the PXR-3′UTR single nucleotide polymorphisms and previously identified intron single nucleotide polymorphisms. Although CL/F differences were not statistically significant within the entire study cohort, African-American carriers of Haplotype-1 (which includes both rs3732359 and rs3732360 variants) exhibited 70% higher median CL/F compared with African-American non-carriers (p?=?0.036).

5. The results identify rs3732359 and rs3732360 as PXR-3′UTR single nucleotide polymorphisms associated with higher CYP3A activity in vivo in African-Americans.

     

鞍区脑膜瘤的磁共振诊断

目的探讨鞍区脑膜瘤的磁共振征象及诊断价值。方法回顾性分析27例经手术切除和病理证实的鞍区脑膜瘤,行MRI平扫和增强扫描。观察其影像学表现。结果 27例患者中女性21例,男性6例。位于鞍旁10例,鞍上17例。27例肿瘤在T1WI上均呈等或略低信号,T2WI呈等或略高信号;25例边界较清晰,2例边界欠清晰;增强后24呈明显均匀强化,3例呈不均匀强化;24例见脑膜尾征。结论鞍区脑膜瘤的MRI表现较具特征性,MRI在该病的术前诊断中具有重要作用。     

64排螺旋CT在颌面部外伤的诊断价值

【摘要】目的总结分析说明64排螺旋CT在急诊检查中合理应用多平面重建（MPR）、容积再现（VR）技术的重要性。方法回顾性分析53例颌面部外伤患者的平片、64排螺旋CT多种重建图像,发现MPR、VR在急诊诊断中具有平片及普通CT不可替代的作用。结果53例经64排螺旋CT扫描重建后所有病例均发现了骨折,其中有5例鼻骨DR侧位平片未见明确骨折者。经MPR重建不仅可以清晰地显示骨折空间移位、重叠程度,而且可以准确地测量出具体数值,而VR可以立体直观地显示出骨折线的走形方向、骨碎片的数目及与邻近组织的空间关系。结论在急诊检查中合理利用64排螺旋CT的各项重建技术不仅可以避免漏诊情况的出现,而且也可以为临床充分了解损伤情况,制定出严谨的治疗方案提供jf{足够多的影像依据,因此64排螺旋CT重建技术可做为急诊影像检查的常规检查手段。     

基底节区胶质瘤的手术治疗分析

目的 分析侵犯基底节区胶质瘤的临床特点、手术效果.方法 对本院2007年6月～2012年6月手术切除的10例侵犯基底节区的胶质瘤患者的临床表现、手术治疗效果及预后进行回顾性分析.结果 本组患者全部完成显微镜下肿瘤全切.有2例患者出现肢体偏瘫症状或偏瘫加重,1例患者暂时性动眼神经麻痹,其他患者均恢复良好或症状未加重.术后随访发现患者生存质量良好,1年内无复发情况.结论 对基底节区胶质瘤应当采取手术全切为主的综合治疗方案.     

Novel Hybrid-Type Antimicrobial Agents Targeting the Switch Region of Bacterial RNA Polymerase

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Background

Navigated transcranial magnetic stimulation (nTMS) has been proven to influence surgical indication and planning. Yet there is still no clear evidence how these additional preoperative functional data influence the clinical course and outcome. Thus, this study aimed to compare patients with motor eloquently located supratentorial lesions investigated with or without preoperative nTMS in terms of clinical outcome parameters.

Methods

A prospectively enrolled cohort of 100 patients with supratentorial lesions located in motor eloquent areas was investigated by preoperative nTMS (2010–2013) and matched with a control of 100 patients who were operated on without nTMS data (2006–2010) by a matched pair analysis.

Results

Patients in the nTMS group showed a significantly lower rate of residual tumor on postoperative MRI (OR 0.3828; 95% CI 0.2062–0.7107). Twelve percent of patients in the nTMS and 1% of patients in the non-nTMS group improved while 75% and 81% of the nTMS and non-nTMS groups, respectively, remained unchanged and 13% and 18% of patients in the nTMS and non-nTMS groups, respectively, deteriorated in postoperative motor function on long-term follow-up (P = .0057). Moreover, the nTMS group showed smaller craniotomies (nTMS 22.4 ± 8.3 cm²; non-nTMS 26.7 ± 11.3 cm²; P = .0023).

Conclusions

This work increases the level of evidence for preoperative motor mapping by nTMS for rolandic lesions in a group comparison study. We therefore strongly advocate nTMS to become increasingly used for these lesions. However, a randomized trial on the comparison with the gold standard of intraoperative mapping seems mandatory.     

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