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1.
《Drug metabolism and pharmacokinetics》2020,35(1):56-70
Hepatic uptake mediated by organic anion transporting polypeptide (OATP) 1B1 and 1B3 can serve as a major elimination pathway for various anionic drugs and as a site of drug-drug interactions (DDIs). This article provides an overview of the in vitro approaches used to predict human hepatic clearance (CLh) and the risk of DDIs involving OATP1Bs. On the basis of the so-called extended clearance concept, in vitro–in vivo extrapolation methods using human hepatocytes as in vitro systems have been used to predict the CLh involving OATP1B-mediated hepatic uptake. CLh can be quantitatively predicted using human donor lots possessing adequate OATP1B activities. The contribution of OATP1Bs to hepatic uptake can be estimated by the relative activity factor, the relative expression factor, or selective inhibitor approaches, which offer generally consistent outcomes. In OATP1B1 inhibition assays, substantial substrate dependency was observed. The time-dependent inhibition of OATP1B1 was also noted and may be a mechanism underlying the in vitro–in vivo differences in the inhibition constant of cyclosporine A. Although it is still challenging to quantitatively predict CLh and DDIs involving OATP1Bs from only preclinical data, understanding the utility and limitation of the current in vitro methods will pave the way for better prediction. 相似文献
2.
目的总结胸腺切除术治疗老年及老年前期重症肌无力的临床效果。方法对1981年~2001年在我院行胸腺切除治疗的23例老年及老年前期重症肌无力患者的手术疗效进行回顾分析。结果在所有重症肌无力患者中老年及老年前期患者所占比例小,男性为多见;全身型为主,合并胸腺瘤及危象者多;手术总有效率43.5%。结论老年及老年前期重症肌无力的手术疗效较青壮年为差,但仍是可选择的一种重要方法。 相似文献
3.
扩大经蝶入路进入海绵窦内侧腔的应用显微解剖 总被引:1,自引:0,他引:1
目的为临床开展扩大经蝶入路进入海绵窦内侧腔手术提供解剖学依据。方法用50例成人头颅标本.在显微镜下对蝶窦外侧壁、蝶鞍、海绵窦及周围结构进行解剖学观察并测量。模拟扩大经蝶入路磨除海绵窦腹侧骨质,切开海绵窦内侧壁,显露海绵窦内侧腔。结果颈内动脉(ICA)明显隆起于蝶窦侧壁的占58%,蝶窦内隆起呈管型占3%。鞍底硬膜分为2层,海绵窦内侧壁的上部南垂体硬膜构成,无骨性结构支撑;下部由骨周硬膜构成,有蝶窦侧壁骨质支撑。两侧海绵窦内侧壁的距离为(14.8±2.7)mm。海绵窦内侧腔位于C4段ICA与垂体之间,腔内为丰富的静脉丛,最宽可达7mm,但常因ICA扭曲而闭塞。无颅神经穿越海绵窦内侧腔,ICA是扩大经蝶入路探查海绵窦遇到的第一个主要结构。结论扩大经蝶入路进入海绵窦内侧腔是安全可行的。 相似文献
4.
M. Giagheddu G. Puggioni G. Sanna G. Tamburini F. Marrosu M. G. Rachele B. Murgia G. Rosati 《Acta neurologica Scandinavica》1989,79(4):326-333
From 1.1.1958 to 31.12.1986, 110 cases of MG were observed in Sardinia, with a mean annual incidence of 2.5 x 1,000,000 inhabitants and prevalence rates of 7.5, 17.6, 31.4 and 45.0 x 1,000,000 inhabitants respectively (prevalence days: 15.10.1961, 24.10.1971, 25.10.1981 and 31.12.1986). The disease was found to be more frequent in women. There were no differences in the distribution of MG in various areas of the island. The muscle group more frequently involved at onset was the ocular. In 6.4% of patients an association with thyroid disorders was observed. The mortality of MG patients was significantly higher than expected. Removal of the thymus, carried out in 58 patients, was shown to be useful in the treatment of the disease, particularly in patients without thymomas. No familial cases were observed. 相似文献
5.
Summary
The compartment syndrome (cs) is characterized by an increased tissue pressure in a limited space. Pathophysiologically, it
is a multifactorial disease that is potentially induced by an initial trauma and develops according to the existence of cofactors.
Cofactors are, for instance, the circulation of the patient and the initial treatment of the impending cs. In particular,
the microcirculation is altered with endothelial destruction, development of a capillary leak, protein loss from intravasal
space and the development of an interstitial and intracellular third space. An impaired drainage of the lymphatic and venous
system causes a venous infarction. An arterial infarction results if the tissue pressure exceeds the arteriolar pressure.
An accompanying ischemia reperfusion mechanism increases the trauma load. In disadvantageous cases, the patients are in danger
of developing a multi-organ deficiency syndrome (MODS) by an uncontrolled inflammatory reaction, by intravasal volume loss
and by a myonephropathic systemic reaction. Clinically, the patients suffer a disproportionate amount of pain, followed by
neurological signs. Especially in noncompliant patients, tissue pressure measurement is useful. Resuscitation of the circulation
as well as splitting of casts is important. In case of a manifest cs, dermatofasciotomy has to be performed as an emergency
operation. Even if cs is diagnosed early and fasciotomy is carried out early, the development of sequellae cannot be avoided
in every single case.
相似文献
6.
Exacerbation of myasthenia gravis after removal of thymomas 总被引:6,自引:0,他引:6
F. E. Somnier 《Acta neurologica Scandinavica》1994,90(1):56-66
It appeared from this prospective and non-randomized study, that the removal of thymomas in myasthenia gravis (MG) patients resulted in rapid exacerbation of the clinical severity of the disease and of anti-acetylcholine receptor antibodies titres, which peaked after about 300 days and continued for up to 2 years. Long-term follow-up after thymomectomy (mean duration ± SEM after surgery 5.5 ± 0.8 years) showed that the immunological and clinical state observed prior to surgery was eventually restored, but long-term benefit attributable to surgery could not be demonstrated. Non-thymoma MG cases, however, exhibited post-operative amelioration in clinical course and decreasing antibodies titres, both of which were already significant one year after surgery, and additional improvement was observed at the time of long-term follow-up (mean 4.3 ± 0.5 years). Furthermore, the prognosis for MG patients not operated on was also favourable. It is suggested that the occurrence of thymomas is linked to genetic factors and that neoplasia of the thymus may be part of immunoregulatory mechanisms with predominance of inhibition. 相似文献
7.
Effects of surgical treatment in thymoma with myasthenia gravis: our experience in 103 patients. 总被引:3,自引:0,他引:3
F Crucitti G B Doglietto R Bellantone V Perri O Tommasini P Tonali 《Journal of surgical oncology》1992,50(1):43-46
A retrospective study of 103 thymectomies examines the effects of the integration of surgical and medical therapy in patients affected by myasthenia gravis accompanied by thymoma. An extended thymectomy via a median longitudinal sternotomy was used in 102 patients. The operative mortality was 4.85% (5/103 patients), the 10-year survival rate was 78% with a recurrence rate of 3.06% (3/98). Neoplastic infiltration and postoperative radiotherapy did not influence the survival rate. There was no correlation between a preoperative Osserman's class better than III and postoperative outcome. The improvement of medical treatment, and anaesthesiological and intensive care techniques resulted in a decrease of the operative mortality and long-term death rate during the last 10 years of our 20-year series. Extended thymectomy via sternotomy is the best intervention in patients with myasthenia gravis associated with thymoma judged by the low operative mortality and the favorable 10-year survival rates. 相似文献
8.
Michael B. Farnell Gerard V. Aranha Yuji Nimura Fabrizio Michelassi 《Journal of gastrointestinal surgery》2008,12(4):651-656
With improvements in the safety of Whipple resection in recent decades, surgeons have continued to explore the role of more
extensive lymphadenectomy in hope of improving long-term survival. A systematic literature search of level I evidence addressing
the role of the extent of lymphadenectomy was undertaken. Only reports of prospective, randomized controlled trials comparing
pancreaticoduodenectomy with standard lymphadenectomy to pancreaticoduodenectomy with extended lymphadenectomy where information
regarding survival, morbidity, mortality, the number of resected lymph nodes in each group and detailed operative technique
were included. Four prospective, randomized trials comprising some 424 patients and one meta-analysis were identified. In
aggregate, these studies confirmed that the number of resected lymph nodes was significantly higher in the pancreaticoduodenectomy
with extended lymphadenectomy group. Morbidity and mortality rates were comparable. Postoperative diarrhea in the early months
after operation was problematic in patients undergoing extended lymphadenectomy. In none of the studies was a benefit in long-term
survival demonstrated. Standard pancreaticoduodenectomy continues to be the operation of choice for adenocarcinoma of the
head of the pancreas.
Presented at The Society for Surgery of the Alimentary Tract Postgraduate Course “Systematic Reviews of Pancreaticobiliary
Disease Customized for the Gastroenterologist and Gastrointestinal Surgeon” on May 20, 2007, Washington, D.C. 相似文献
9.
运用变性高效液相色谱对肺炎克雷伯菌产ESBL进行基因分型 总被引:24,自引:1,他引:24
目的 通过运用变性高效液相色谱(DHPLC)技术对前期研究已确认产超广谱β-内酰胺酶(ESBL)的肺炎克雷伯菌临床分离株TEM型质粒进行基因分型,试图建立一种方便快捷的用于ESBL分子诊断及其流行病学监测的新方法.方法 利用PCR技术从肺炎克雷伯菌临床分离株中扩增出TEM型质粒的编码序列,扩增产物运用DHPLC技术进行分析,分析提示,异常的样本通过测序确定其基因突变的类型,最后通过比对确定其基因型.结果 共分析了101例肺炎克雷伯菌临床分离株,全部样本均扩增出TEM型质粒的编码序列,经过DHPLC分析,52例(51.4%)样本表现为单一的洗脱峰,其形态与TEM-1标准菌株的峰型相一致,测序确定它们的碱基序列亦相一致,不存在变异,为TEM-1型;49例(48.6%)样本表现为异常的洗脱峰,它们均为双峰,形态一致,但异源双链峰的高度有差异,测序结果表明它们均存在四种相同的基因突变,在NCBI网站比对后确定为TEM-116;测序结果还提示,部分样本中TEM-1和TEM-116混合存在,其比例的不同表现为DHPLC时异源双链峰高度的差异;文献检索表明,本次确定的TEM-116为一新的基因亚型,为国内首次报道.结论 DHPLC具有简便快捷、高通量和自动化的特点,重复性好,不仅可对已知突变作出即时诊断,还可发现新的基因亚型,不失为一种较好的ESBL分子诊断方法及其流行病学监测手段. 相似文献
10.
华南地区质粒介导超广谱β-内酰胺酶的基因分型研究 总被引:59,自引:4,他引:59
目的:了解华南地区质粒介导超广谱β-内酰胺酶(ESBLs)的发生率及基因型特征。方法:收集2001年4月-9月革兰阴性菌临床分离无重复株共1184株,采用NCCLS表型筛选和确认试验进行了ESBLs产酶的识别,E-test法检测各亚型ESBLs的MICs值,质粒接合及电转化实验,耐药质粒提取及酶切指纹分析,等电聚焦电泳,PCR通用引物扩增TEM、SHV、CTX-M、VEB、PER、SFO基因及其克隆测序进行ESBLs基因分型和质粒定位。结果:革兰阴性苗ESBLs的检出率为14.6%(173/1184);获得产ESBLs接合子67株,电转化子11株,其中产CTX-M-14型ESBLs为33.3%(26/78)、CTX-M-3为23.1%(18/78)、CTX-M-9为14.1%(11/78)及SHV-2a为2.6%(2/78),未定型为5.1%(4/78);29.5%(23/78)野生株伴广谱酶TEM-1或SHV-1型;各型ESBLs基因约定位在35-190kb大小的可接合性低执行者拷贝数天然质粒上;CTX-M型ESBLs以对头孢噻肟高水平高耐为特征。结论:华南地区质粒介导的ESBLs以CTX-M型衍生酶为主,其次是SHV型酶。 相似文献