Pharmacokinetics and haemodynamic effects of ISDN following different dosage forms and routes of administration

The pharmacokinetics and haemodynamic effects of isosorbide dinitrate (ISDN) have been investigated following administration of single doses as a sublingual (SL) spray (2.5 mg), sublingual tablet (5 mg) and peroral tablet (10 mg) in a randomised, placebo-controlled double-blind cross-over trial in 16 healthy volunteers.After the sublingual spray C_max was higher (39.0 ng·ml^-1) and t_max was shorter (3.9 min) than after the sublingual (22.8 ng·ml^-1 and 13.8 min) and peroral (16.9 ng·ml^-1 and 25.6 min) tablets. The AUC of ISDN did not differ following any of the three formulations (1031; 879; 997 ng·ml^-1·min, for the spray, SL tablet and PO-tablet, respectively). Mononitrate metabolites of ISDN (IS-2-MN and IS-5-MN) and total nitrates in plasma increased in proportion to the administered dose. This indicates that the fraction of the dose absorbed was the same for all the formulations but that the extent of first-pass metabolism increased in the order sublingual spray < sublingual tablet < peroral tablet. Thus, compared to the spray, the relative bioavailability of ISDN was 48% and 28% from the sublingual and peroral tablets, respectively.The haemodynamic effects were quantified using the a/b ratio of the finger pulse wave and the systolic blood pressure and heart rate under orthostatic conditions. For the a/b ratio of the finger pulse, the maximal effect was higher (e_max=130%) and the time to e_max (t_emax) shorter (16.6 min) after the spray than the sublingual tablet (84.4% and 25.5 min) or peroral tablet (90.2 and 31.3 min). The onset of effect was within 3, 5 and 7.5 min after the spray, sublingual and peroral tablets, respectively. A larger change in the orthostatically-induced decrease in systolic blood pressure and increase in heart rate was obtained following peroral than sublingual administration despite the similar plasma concentrations of ISDN. This probably reflects the larger amount of pharmacodynamically active mononitrate metabolites formed after oral dosing. The integrated effect following administration of 2.5 mg ISDN as spray was similar to that of a sublingual tablet of 5 mg.     

Flexor digitorum profundus tendongrafting (extrasynovial donor tendons)

Although the prevalence of flexor tendon grafting has decreased since the early part of this century, the technique isstill an important part of a hand surgeons armamentarium. Primary and staged flexor tendon grafting are appropriate techniques used to restore digital function after failed or neglected repairs. Appropriate patient selection, meticulous reconstructive techniques, and respect for basic biological principles of healing and repair are essential elements for successful tendon grafting.     

536例大肠癌误诊误治分析

大肠癌误诊误治较为普通。从总结经验教训出发，本文对确诊前曾发生过误诊误治的５３６例大肠癌进行详尽的分析。本组病例５３６例，曾７１９次先后被误诊为３２种疾病，其中误诊为“痔”“痢疾”“肠炎”“肠梗阻”等最为常见，误诊为其它疾病也时有发生，严重的影响其预后。在误诊原因上，除病人自误外，与医生责任心不强，询问病史不细，本行或未认真行有关检查，特别是直肠指诊检查和结肠内窥镜检查是分不开的。文章就今后如何减少误诊，提高早期诊断率，提出了５点措施，强调了直肠指诊和结肠内窥镜检查的重要价值。     

Levodopa improves physical fatigue in Parkinson's disease: a double-blind, placebo-controlled, crossover study.

We quantitatively investigated the effect of carbidopa/levodopa (25/100) on physical fatigue during finger tapping and force generation in a double-blind, placebo-controlled crossover study. Parkinson's disease (PD) subjects were randomly assigned to carbidopa/levodopa or placebo for Visit 1 or 2 and participated in the following two studies: (1) Finger tapping. Twenty-five PD patients used their index fingers to strike two keys 20 cm apart on a musical instrument digital interface (MIDI) keyboard. The slopes of the regression line of dwell time and movement time were used to assess the rate of fatigue development. (2) Force generation. Twelve PD patients contracted the wrist extensors maximally to obtain a baseline maximum voluntary contraction (BMVC) force. Then they repetitively contracted the wrist extensors at 50% of the BMVC for 7 seconds and rested for 3 seconds. An interval maximum voluntary contraction (IMVC) was measured every three repetitions. Fatigue was defined as an IMVC of less than 60% of the BMVC. The slope of the regression line of IMVC was used to assess the rate of force decline. These two studies were repeated 1 hour after carbidopa/levodopa (25/100) or placebo. Subjects filled out the Multidimensional Fatigue Inventory (MFI) at the beginning of the first visit. Results showed that the slope of dwell time decreased with levodopa but not with placebo (P = 0.004). The rate of force decline also decreased with levodopa but not with placebo (P = 0.01). The subscores in the dimension of physical fatigue in the MFI did not correlate with the rate changes in dwell time or the rate changes in force decline. We concluded that (1) levodopa improves physical fatigue in finger tapping and force generation, (2) physical fatigue in Parkinson's disease is at least partially related to dopamine deficiency, and (3) the MFI measures different aspects of physical fatigue compared with those measured by finger tapping and force generation.     

环指屈肌腱损伤吻接术前、后力学性能测试研究

研究正常环指屈肌腱拉伸力学性能和模拟屈肌腱损伤后吻接术后屈肌腱的力学性能,为临床提供生物力学参数。取10个手环指标本,解剖后暴露环指,将标本固定于电子万能试验机底座上,由钢丝绳吊钩沿屈肌腱纵行方向钩住、钢丝绳上端固定于试验机上夹头上,驱动机器,对标本进行拉伸实验,施加拉应力,直至屈肌腱断裂。对断裂后的屈肌腱模拟临床手术进行移位吻接,对10个标本做了腱与腱移位吻接。再对吻接后的标本进行拉伸实验。分别得出了正常组标本和吻接术后标本的拉伸最大载荷、应力、应变等数据。表明:屈肌腱腱与腱吻合组最大载荷、应力、应变均小于正常对照组,但模拟末端编织法吻接术腱与腱吻合组标本,仍具有较好的拉伸力学性能指标。     

指屈肌腱腱纽的显微解剖 Ⅱ、腱纽的动脉和神经

本文解剖观察了30只手共150个手指的腱纽内动脉和神经。进入肌腱的动脉和神经都是手指两侧的指掌侧固有动脉和指掌侧固有神经的分支,它们穿过腱纤维鞘裂孔进入腱纽,然后再分支到屈指肌腱。动脉和神经在进入腱纽的起始处有脂肪团,可作为寻找腱纽内动脉与神经的标志。至拇指腱纽的动脉和神经是在第一指骨底至第一指骨头之间进入腱鞘,其它的指一般一个手指有四组动脉、两组神经分别进入每个手指的四型腱纽,而进入腱鞘的位置分别在:一指底,一指中间1/3与远侧1/3的交接处,二指底,二指头。其中Ⅱ、Ⅳ型的动脉有神经伴行。     

静脉动脉化再植拇指完全离断

目的 报道静脉动脉化再植拇指完全离断的新方法。方法 1999—2002年在5例拇指完全离断再植手术中，因指动脉严重损伤或多次吻合指动脉失败后，将近侧动脉与断指的一条静脉吻合作为供血通路，近侧的静脉与断指的另几条静脉吻合作为回血通路。结果 5例再植拇指全部成活，早期病例完全恢复了良好的功能。结论 静脉动脉化是一种拇指离断再植的新方法，操作简便，效果可靠，值得推广应用。     

内镜下切断屈肌支持带远侧纤维束治疗腕管综合征

目的探讨内镜下腕管切开减压术（endoscopic carpal tunnel release，ECTR）中切断屈肌支持带远侧纤维束（distal holdfast fibers of the flexor retinaculum，DHFFR）的必要性。方法观察组16例，臂丛神经阻滞麻醉，不使用止血带，皮肤1cm切口，内镜下应用USE系列切断腕管横韧带和DHFFR，与对照组16例单纯切断腕管横韧带进行疗效比较。结果术后6个月功能随访，按照Kelly疗效评定标准，观察组优13例，良3例；对照组优8例，良5例，可3例，2组浜田Ⅱ、Ⅲ级疗效差异有显著性（，=6．278，P=0．043）。2组均无严重并发症及术后复发。结论对浜田Ⅱ、Ⅲ级腕管综合征者术中注意腕横韧带切断不是唯一的目标，同时切断DHFFR才能彻底减压。     

指背血管蒂逆行岛状皮瓣的临床应用

目的：探讨一种新的方法修复手指部皮肤软组织缺损。方法：以手指背血管为蒂，于近节指背、指蹊及掌背远端区域设计逆行岛状皮瓣转移至手指皮肤软组织缺损处，皮瓣及蒂部包涵指背动脉及指背浅静脉，皮瓣供区可直接拉拢缝合或皮片移植修复。结果：1999年10月～2002年8月，临床应用12例13个皮瓣，11个皮瓣完全成活，2个皮瓣发生表皮层坏死，经换药后自愈。结论：指背血管蒂逆行岛状皮瓣邻近手指皮肤软组织缺损区，血运可靠，可以安全、简便地修复手指创面。     

手指离断再植术后护理

目的 探讨断指再植护理措施。方法 采用指体的摆放，病房适宜温度20～25℃，烤灯局部保温，术后观察血运指标，小儿特殊护理及康复指导。结果 成活优良率91．6％，住院天数平均16天，功能恢复满意率75％。结论 护理措施恰当，可显降低并发症的发生，提高治愈率。