阵发性心房颤动的射频导管消融大静脉电隔离治疗

目的报道阵发性心房颤动(房颤)的射频导管消融电隔离肺静脉和腔静脉的疗效。方法阵发性房颤患者36例,年龄(42.5±13.2)岁。经1次房间隔穿刺放置环状标测电极导管(Lasso导管)和冷盐水灌注消融导管,在Lasso导管的指导下,采用全肺静脉或上腔静脉与靶静脉节段性电隔离相结合的方法对肺静脉和腔静脉行标测和电隔离治疗。窦性心律时最早激动的肺静脉和腔静脉电位处和/或心房起搏时最短的心房和静脉电位间期处为靶点行消融。结果36例阵发性房颤患者均接受一次电隔离治疗,共电隔离大静脉115根,其中左上肺静脉34根,左下肺静脉22根,右上肺静脉30根,右下肺静脉17根,上腔静脉12根,即刻电隔离成功率为95.6%,术中并发症发生率2.78%。随访3~22个月,成功率(无房颤发作或房颤发作明显减少)为75.0%。结论射频导管消融电隔离肺静脉或腔静脉与心房间的电活动连接,可有效预防房颤的复发。治疗的关键是消融靶点的标测和确定。     

Islet transplantation in IDDM patients

Summary This single-centre study investigated parameters that positively correlated with the success rate after islet allotransplantation in insulin-dependent diabetic (IDDM) patients. Twenty-one intrahepatic, fresh islet transplantations were performed in 20 IDDM patients (one patient had two transplants), after or simultaneous with kidney transplantation. The correlation between number and purity of transplanted islets and final outcome was investigated. One patient died of a cardiac arrest several hours after islet transplantation; this patient was not included in the follow-up analysis. Three patients (15 %) experienced acute, irreversible, early failure of islet function, which was considered as a ’presumed rejection'. Nine patients (45 %) achieved either complete insulin-independence (seven cases) or a reduction (> 50 %) of exogenous insulin requirement (two cases), with sustained serum C-peptide secretion (0.89 ± 0.04 nmol/l; duration: 21 ± 7 months, range 2–58 months). Liver biopsy, performed 3 years after transplantation in one successful case, showed normal islets within the hepatic parenchyma. Eight cases (40 %) did not show any metabolic effect of islet transplantation, with low serum C-peptide levels (’presumed function exhaustion'). Metabolic investigations performed in successful cases showed an early phase of insulin release after arginine, mild and reversible postprandial hyperglycaemia and normal HbA_1c levels. Success of islet transplantation positively correlates with the number (p < 0.05) of the transplanted islets. Islet transplantation is a safe procedure, with 45 % success rate, in terms of insulin-independence or relevant reduction of exogenous insulin requirement, although success can be transient. [Diabetologia (1997) 40: 225–231] Received: 20 June 1996 and in final revised form: 28 October 1996     

A prospective study of isolation and mortality in a cohort of elderly Navajo Indians

The prospective association between social isolation and mortality in a sample of 271 elderly Navajo Indian men and women living on their reservation in northern Arizona is reported. The follow-up period averaged three years from the time of interview in 1982–3. Self-reported level of physical functioning was predictive of mortality. Of the psycho-social measures, only marital status among men was predictive of increased risk of death, with the unmarried being at higher risk than the married. These results are attributed to the fact that Navajo society is traditionally matrilineal and matrilocal, with the mother-daughter bond being especially significant and with men being relatively more peripheral than their wives to the kin group. Thus unmarried men are far more likely to be isolated from kin than unmarried women and married people of either sex.     

阵发性心房颤动患者上腔静脉肌袖与心房的电学连接特征

总结 16例阵发性心房颤动患者上腔静脉 (SVC)肌袖的电生理标测和导管射频消融电隔离的结果 ,评价SVC肌袖和心房电连接的类型和特点。在环状标测电极指导下 ,对 16根SVC肌袖进行电位的记录、分析以及开口部的点或段的消融电隔离治疗。根据窦性心律和心房起搏下的肌袖内环形电极标测的袖电位激动顺序 ,即电突破点的数目和位置 ,以及有效放电对袖电位及其电突破点的影响 ,总结和分析袖房之间的电连接类型和特点。结果 :共标测和电隔离SVC肌袖 16根。其中呈单束状电连接 8根 (5 0 % ) ,双束状电连接 7根 (43.7% ) ,多束状电连接 1根 (6 .3% )。 16根SVC平均每根电连接束为 1.6± 0 .6根 ,共消融 2 .1± 0 .6个节段和部位 ,每个部位进行了2 .3± 0 .7次的放电。所有病例均达到完全电隔离的标准。结论 :SVC袖房之间电连接的类型多为单束状和双束状 ,在袖房连接处行点或节段性消融即可达到完全袖房电隔离的结果。     

Isolation and determination of absolute configurations of insect-produced methyl-branched hydrocarbons

Although the effects of stereochemistry have been studied extensively for volatile insect pheromones, little is known about the effects of chirality in the nonvolatile methyl-branched hydrocarbons (MBCHs) used by many insects as contact pheromones. MBCHs generally contain one or more chiral centers and so two or more stereoisomeric forms are possible for each structure. However, it is not known whether insects biosynthesize these molecules in high stereoisomeric purity, nor is it known whether insects can distinguish the different stereoisomeric forms of MBCHs. This knowledge gap is due in part to the lack of methods for isolating individual MBCHs from the complex cuticular hydrocarbon (CHC) blends of insects, as well as the difficulty in determining the absolute configurations of the isolated MBCHs. To address these deficiencies, we report a straightforward method for the isolation of individual cuticular hydrocarbons from the complex CHC blend. The method was used to isolate 36 pure MBCHs from 20 species in nine insect orders. The absolute stereochemistries of the purified MBCHs then were determined by digital polarimetry. The absolute configurations of all of the isolated MBCHs were determined to be (R) by comparison with a library of synthesized, enantiomerically pure standards, suggesting that the biosynthetic pathways used to construct MBCHs are highly conserved within the Insecta. The development of a straightforward method for isolation of specific CHCs will enable determination of their functional roles by providing pure compounds for bioassays.The use of chemical signals is highly developed within insects, with semiochemicals mediating a wide variety of inter- and intraspecific behaviors. Volatile pheromones, such as sex and aggregation pheromones, are the most well-known types, but insects also use nonvolatile cuticular lipids as contact pheromones (1–4). The cuticular lipids consist of a complex blend of n- and methyl-branched alkanes, alkenes, and lesser amounts of more polar compounds such as esters and alcohols. The lipid layer acts primarily as a waterproofing barrier (5), but individual lipid components have evolved secondary roles as signals that mediate a variety of behaviors and physiological changes (1, 2, 6). For example, solitary insects use cuticular hydrocarbons (CHCs) to identify the species and sex of mates (7, 8) whereas, in social insects, CHCs mediate identification of nestmates (9, 10), recognition of castes, and task allocation within the colony (11). Social insect queens also use CHCs to signal fecundity and dominance status within the colony, inhibiting development of workers into reproductives (12–14).Determining the roles of specific CHCs as signals has been hindered by three interlinked problems. First, CHCs typically consist of a large number of compounds, which can be difficult to isolate in pure form to test their bioactivities. Specifically, CHCs have very similar polarity and so are not separable by liquid chromatography on silica gel or other polar chromatographic media. Conversely, the compounds are so hydrophobic that they are insoluble in the aqueous-organic solvent systems typically used with reverse phase chromatography. Whereas most CHCs can be separated to some degree by analytical gas chromatography (GC), isolation by preparative GC is challenging because of the high temperatures required and the difficulty in eliminating cold spots at the interface of the GC column with the collection apparatus, which can ruin the separation.In contrast, reverse phase high performance liquid chromatography (RP-HPLC) using nonaqueous solvent systems has excellent potential for isolating CHCs from complex blends because the separation depends primarily on hydrophobic interactions between the solutes and the stationary phase. Thus, homologous CHCs should be readily separable on the basis of chain length, presence or absence of double bonds, and chain branching. However, there is a second problem, one of detection, because most HPLC detectors are poorly sensitive or insensitive to CHCs. HPLC coupled to mass spectrometry also is problematic because alkanes and alkenes are only poorly ionized or not ionized at all by electrospray or other ionization methods typically used with HPLC-MS, and so are invisible to the mass spectrometer.The third problem concerns the inherent chirality of methyl-branched CHCs, most of which can exist in two or more stereoisomeric forms, depending on the number of branches and their positions. The correct stereochemistry is integral to the activity of most bioactive molecules. Insects are no exception, with numerous examples known of the natural stereoisomer of a volatile pheromone eliciting the expected bioactivity whereas other stereoisomers can vary from eliciting hyperactivity to being strongly inhibitory (3, 4).Methyl-branched cuticular hydrocarbons (MBCHs) have been identified or implicated as contact pheromones in a number of insect species (15–27), but most studies involving MBCHs have ignored the issue of stereochemistry and used only racemic MBCHs in bioassays to assess function. The linked questions as to whether insects biosynthesize MBCHs enantioselectively and whether insects can discriminate between the stereoisomeric forms of MBCHs are still largely unknown (28). This deficiency is due to the difficulty in determining the absolute configurations of insect-produced MBCHs, particularly when produced in only nanogram to microgram amounts per individual. In particular, MBCH enantiomers do not separate on chiral stationary phase chromatography columns due to their lack of functional groups or other structural features that interact strongly enough with the chiral stationary phase to permit resolution (29–31).As an alternative, the specific rotations of compounds can be measured with a polarimeter and the absolute stereochemistry determined by comparing the measured rotations to those of enantiopure standards. However, this method is useful only if compounds can be isolated in pure form. Furthermore, the specific rotations of MBCHs are small (a few degrees-cm²/g for 3-methylalkanes) and decrease further as the methyl branch is moved toward the middle of the chain, requiring isolation of milligram quantities of each MBCH to obtain a measurable rotation. Thus, a method of isolating individual, pure MBCHs in milligram amounts is a prerequisite to the determination of their stereochemistry.We describe here a straightforward solution to this nested series of problems. Crude extracts of insect cuticular lipids were first separated into straight-chain alkanes, methyl-branched alkanes, alkenes, and more polar compounds by known fractionation methods (32–34). Reverse phase HPLC with nonaqueous solvent systems and an evaporative light-scattering detector (ELSD), a “universal” detector that detects any nonvolatile molecule, then allowed isolation of individual components from these fractions. This methodology was used to isolate MBCHs from 20 insect species from nine orders, including adults of both sexes from both holometabolous and hemimetabolous species, and of several different life stages, and the absolute configuration of each compound was determined by polarimetry. The separation protocol was extended to the isolation of individual alkenes from CHC extracts to demonstrate its general utility in isolating pure components from the CHC blend.