ER基因多态性与中国南方妇女绝经后骨质疏松症的病例-对照研究

目的对中国南方绝经后妇女中雌激素受体基因PvuⅡ和XbaⅠ核酸限制性内切酶多态性与骨质疏松症的关系进行了病例一对照调查。方法中国南方绝经后妇女182人，分为骨质疏松组和正常对照组，每组91人；均用DEXA检测骨密度，用PCR—RFLP的方法鉴定雌激素受体的基因型，分析雌激素受体基因多态性与骨密度的关系及各基因型在骨质疏松组与对照组的分布。结果PP、xx、Ppxx、PPxx型在骨质疏松组中的分布频率高于正常对照组，差异有统计学意义。PP、xx、Ppxx、PPxx四种基因型的携带者比正常人骨质疏松的易患程度分别高2．46、2．972、2．2、15倍。结论可以将ER基因PvuⅡ和XbaⅠ多态性作为在中国南方进行筛选绝经后骨质疏松症的高危人群的依据之一。     

雌激素受体基因多态性与中国南方妇女绝经后脊柱骨质疏松症的关系

目的 对中国南方绝经后妇女雌激素受体（ER）基因PvuⅡ和XbaⅠ核酸限制性内切酶多态性与脊柱骨质疏松的关系进行病例一对照调查，了解ER基因多态性与妇女绝经后脊柱骨质疏松的关系。方法 182名中国南方绝经后妇女，均用DEXA检测腰椎（L2-5）的骨密度，用PCR—RFLP鉴定雌激素受体的基因型。分析ER基因多态性与骨密度关系以及各基因型在骨质疏松组与对照组的分布。结果 骨密度呈以下分布规律：PP〈Pp〈PP、xx〈Xx〈XX。PP，PPxx，Ppxx的骨密度较其他基因型低。在分层分析中，表明PP型及复合基因型PPxx及Ppxx型在脊柱的骨质疏松组中的分布频率高于对照组，差异有显著性（P〈0．01）。结论 ER基因PvuⅡ和XbaⅠ核酸限制性内Ⅵ酶多态性与骨质疏松存在关系，可以将ER基因PvuⅡ和Xbal多态性作为在中国南方进行筛选绝经后脊柱骨质疏忪高危人群的依据之一。     

安徽地区绝经后妇女雌激素受体基因多态性与骨密度的相关性研究

目的探讨安徽地区绝经后妇女雌激素受体（ER）基因多态性的分布及其与骨密度的相关性。方法随机选择288名安徽合肥地区健康绝经后妇女，运用双能X线骨密度吸收法（DEXA）测定腰椎和股骨颈、大转子骨密度（BMD），并采用PCR-RFLP（聚合酶链反应-限制性片断长度多态性）法分析ER基因多态性，并分析其相关性。结果安徽地区绝经后妇女ER基因型分布频率PP（13．2％）、Pp（45．8％）、pp（40．9％），XX（5．21％）、Xx（31．6％）、xx（63．2％），联合PvuⅡ和XbaⅠ这两种基因型后得到：PPXX（5．6％），PPXx（3．8％），PPxx（6．3％），PpXX（1．4％），PpXx（23．3％），Ppxx（25％），ppxx（34．7％），未检测到ppXX及ppXx型。PvuⅡ多态性与绝经后妇女腰椎BMD相关，PP基因型腰椎BMD显著低于pp和Pp基因型（P〈0．05），ER基因P等位基因是一种有益于骨量的基因型。XbaⅠ多态性与绝经后妇女各部位BMD间无明显相关性（P〉0．05）。联合分析PvuⅡ和XbaⅠ多态性与绝经后妇女BMD相关性发现，有Px单倍型的妇女腰椎部位的BMD显著低于无此单倍型的妇女（P〈0．01）。结论ER基因PVuⅡ多态性与绝经后妇女腰椎BMD有相关性，PP基因型妇女腰椎BMD减低，而具有Px单倍型的ER基因可能对BMD有不利影响。     

雌激素受体基因多态性与骨密度及骨代谢关系的研究

目的研究中国健康绝经后妇女的雌激素受体estrogenreceptorER基因多态性与骨密度bonemineraldensityBMD、骨代谢的关系。方法选取246名中国健康绝经后妇女,年龄44～78岁,平均61岁。运用双能X线骨吸收法分别对其腰椎L1～4和股骨股骨颈N、Ward区W、大转子T的BMD进行测量,并用生物化学的方法测其血清中钙Ca、磷P、碱性磷酸酶ALP、甲状旁腺激素PTH和降钙素CT的含量,用分子生物学的方法分析内切酶PvuⅡ、XbaⅠ限制性片段长度多态性restrictionfragmentlengthpolymorphism,RFLP,观查ER基因多态性与BMD及骨代谢的关系。RFLP用PpPvuⅡ和Xx(XbaⅠ)来表示。结果PPxx基因型BMD明显低于其它基因型。结论ER基因RFLP与绝经后妇女BMD有关,此即为中国妇女绝经后骨质疏松症发病的原因。     

青少年特发性脊柱侧凸患者雌激素受体基因多态性与骨密度的关系

目的探讨青少年特发性脊柱侧凸患者雌激素受体基因多态性与骨密度的关系。方法取青少年特发性脊柱侧凸女性患者92例,年龄10～19岁,Cobb角25°～134°,应用聚合酶链反应限制性片段长度多态(PCRRFLPs)的方法分析雌激素受体基因型,同时用双能X线骨密度吸收仪分别对其腰椎(L24)和股骨近端(股骨颈、大转子、Wards三角)的骨密度进行测量。结果特发性脊柱侧凸患者雌激素受体基因型PvuⅡ多态性PP,Pp,pp型分别为19.6%,46.7%,33.7%,XbaⅠ多态性XX,Xx,xx型分别为22.8%,33.7%,43.5%;XX型的腰椎、股骨大转子和Wards三角的骨密度明显低于xx型(P<0.05),而PvuⅡ基因的各基因型与骨密度无关;联合分析PvuⅡ和XbaⅠ位点,PPXX基因型的腰椎、股骨大转子和Wards三角的骨密度明显低于Ppxx和ppxx型(P<0.05)。结论雌激素受体XbaⅠ基因多态性与特发性脊柱侧凸患者的骨密度有关,PPXX基因型的骨密度较低,有助于较早发现特发性脊柱侧凸的低骨量者。     

雌激素受体α和维生素D受体基因多态性与哈尔滨地区绝经后妇女骨密度的关系

目的探讨哈尔滨市绝经后妇女雌激素受体α(ER-α)基因和维生素D受体(VDR)基因多态性与骨密度的关系。方法对哈尔滨市81例无亲缘关系汉族健康妇女进行PCR-RFLP测定ER-α基因PvuⅡ、XbaⅠ多态性和VDR基因BSMⅠ多态性,用双能X线吸收法测定骨密度(BMD)。结果本研究人群PP、Pp及pp基因型频率分别为13.6%、49.4%、37.0%;XX、Xx及xx基因型频率各为4.9%、40.7%、54.4%;BB、Bb及bb基因型频率各为0%、16.0%、84.0%,t检验分析各基因型与BMD值的关系显示:绝经后妇女中,雌激素受体基因型仅与腰椎骨密度有显著差异。维生素D受体基因型在股骨颈、大转子部位有显著差异。PvuⅡ多态性和BSMⅠ多态性共同作用对骨密度影响更大。结论雌激素受体、维生素D受体基因型分布频率均符合Hardy-Weinberg定律,并且与骨密度有一定的关联,尤其是基因与基因的共同作用与骨密度的关系更为密切。     

雌激素受体基因Pvu Ⅱ多态性对筛选绝经后骨质疏松危险因素的作用

目的 通过雌激素受体基因PvuⅡ基因分型，筛选绝经后骨质疏松的危险因素。方法 检测759例绝经后骨质疏松症者腰椎、股骨上段的骨密度和198例雌激素受体基因PvuⅡ基因型，分析不同基因型的年龄、体重指数等因素与骨密度的相关性。结果 在PP型，低体重是股骨颈、大转子骨密度的危险因素；在pp型，高龄是大转子、Ward’s区骨密度的危险因素；在Pp型，高龄是腰椎、股骨颈、Ward’s骨密度的危险因素；低体重是股骨颈、大转子骨密度的危险因素。结论 通过雌激素受体基因PvuⅡ多态性筛选危险因素对临床防治绝经后骨质疏松有重要的指导价值。     

绝经后妇女桡骨远端骨质疏松性骨折相关因素的研究

目的 探讨绝经后妇女桡骨远端骨质疏松性骨折的危险因素,雌激素受体-α（ER-α）基因多态性与骨密度的关系.方法 以哈尔滨地区自然绝经后妇女108名为研究对象,采用问卷调查的方式,测量腰椎（L2-4）、股骨近端和桡骨远端的骨密度,分为桡骨远端骨质疏松性骨折组、骨质疏松症组和正常对照组.利用PCR-限制性片段长度多态技术检测ER-α基因的PvuⅡ和Xba Ⅰ的酶切多态性,分析基因多态性与骨密度之间的关系.结果 骨折组各部位骨密度均低于正常对照组各部位骨密度,差异有显著统计学意义（P＜0.01）,骨折组与骨质疏松症组各部位骨密度差异无统计学意义（P＞0.05）.Ca、P、AKP在不同组间无统计学意义（P＞0.05）.文化程度高、身高较高、月经初潮较早、钙制剂、牛奶饮用量、VD、体重指数大是桡骨远端骨质疏松性骨折的保护性因素,有统计学意义（P＜0.05）,绝经年龄早、绝经年限长、妊娠次数多、多产次、身高缩短为桡骨远端骨质疏松性骨折的危险因素,有统计学意义（P＜0.05）.ER-α基因PvuⅡ多态性与股骨颈、大转子及桡骨远端骨密度有统计学意义（P＜0.05）,PP基因型较Pp及pp型具有更低的骨密度值,差异有统计学意义（P＜0.05）,Xba Ⅰ多态性与骨密度无相关性（P＞0.05）.结论 文化程度高、身高较高、月经初潮较早、钙制剂、牛奶饮用量、VD、体重指数大是桡骨远端骨质疏松性骨折的保护性因素,绝经年龄早、绝经年限长、妊娠次数多、多产次、身高缩短为桡骨远端骨质疏松性骨折的危险因素.ER-α基因PvuⅡ多态性与股骨颈、大转子及桡骨远端骨密度具有相关性.     

老年男性髋部骨折患者ERα基因多态性的病例对照研究

目的研究呼和浩特地区汉族老年男性髋部骨折患者雌激素受体基因多态性与骨质疏松症的关系。方法收集老年男性髋部骨质疏松性骨折128例,按年龄配比选取汉族男性健康体检者128名,进行病例对照研究。所有受试者均行骨密度检查,并进行雌激素受体基因多态性检测。结果骨质疏松组雌激素受体PvuⅡ基因型PP、Pp及pp频率分别为7.8%,42.2%和50.0%;对照组雌激素受体PvuⅡ基因型PP、Pp及pp频率分别为13.3%,53.9%和32.8%,卡方检验提示,骨质疏松组和对照组之间Pp,pp,PP三种基因型的频率分布差异有显著性意义(P<0.05)。骨质疏松组雌激素受体XbaI基因型XX、Xx及xx频率分别为4.7%,44.5%和50.8%;对照组雌激素受体PvuⅡ基因型XX、Xx及xx频率分别为3.1%,39.1%和57.8%,卡方检验提示,骨质疏松组和对照组之间XX、Xx及xx三种基因型的频率分布差异无显著性意义(P>0.05)。结论雌激素受体基因型分布频率均符合Hardy-Weinberg定律,呼和浩特地区老年男性ERα基因基因PvuⅡ酶切位点与原发性骨质疏松症存在相关性。老年髋部骨折与雌激素受体基因多态性可能存在相关性。     

内蒙古地区蒙古族男性雌激素受体基因多态性与骨密度关系的研究

目的 探讨内蒙古地区蒙古族男性雌激素受体a(estrogen receptor,ER)基因多态性与骨密度(BMD)的关系.方法采用PCR- 限制性片段长度多态性检测500名无血缘关系的蒙古族健康男性ER- a基因XbaⅠ和PvuⅡ多态性,结合双能X 线吸收仪检查腰椎(L2-L4)和股骨近端股骨颈( femoral neck)、大转子区( trochanter) 和Ward三角部位BMD.结果 本研究人群XbaⅠ和PvuⅡ等位基因频率分布符合Hardy-Weinberg 定律.PvuⅡ多态性与腰椎(L2-L4)和Ward三角部位BMD 值均有相关性( P<0.05),而XbaⅠ多态性与各部位BMD 值均无相关性; PP基因型在上述部位平均BMD值明显高于Pp和pp 基因型(P< 0.05).结论 本研究结果提示ER-a基因PvuⅡ多态性直接影响蒙古族男性松质骨的骨峰值.     

Is the recovery profile of mivacurium independent of the rate of decay of its plasma concentration in patients with normal plasma cholinesterase activity?

Background: The duration of action of muscle relaxants is poorly correlated to the rate of decay of their plasma concentration. The plasma concentration of mivacurium may rapidly decrease below its active concentration because of the extensive hydrolysis of mivacurium. By inflating a tourniquet on one upper limb for 3 min after the administration of atracurium, mivacurium or vecuronium, we studied the influence of the initial decline of their plasma concentration on their effect. Methods: In 50 patients anaesthetised with thiopental, isoflurane and fentanyl, the effect of bolus doses of 0.15 or 0.25 mg . kg^?1 mivacurium (MIV 15, MIV 25), 0.3 or 0.5 mg . kg^?1 atracurium (ATR 30, ATR 50) and 0.06 or 0.1 mg . kg^?1 vecuronium (VEC 06, VEC 10) were measured on both arms (evoked response of the adductor pollicis to train-of-four stimulation every 12 s), a tourniquet being applied on one arm just before and during 3 min after the muscle relaxant bolus. Results: Tourniquet inflation of 3 min almost abolished the neuromuscular effect of mivacurium. In the vecuronium groups and in the ATR 50 group, tourniquet inflation did not modify the maximum degree of depression of the twitch response. Also, the duration of action of vecuronium was unaffected by the tourniquet. In the ATR 30 group, times to return of the twitch response to 25% (duration 25%) and 75% (duration 75%) of control response were significantly shorter in the cuffed arm, 23 min vs 27 min, and 41 min vs 45 min, respectively. In the ATR 50 group, only duration 25% was significantly shorter in the cuffed arm (41 min vs 45 min). Conclusion: The results suggest that the rate of decline of the plasma concentration of mivacurium is so rapid, that a very low and almost clinically ineffective concentration is present as soon as 3 min after its administration. The results also indicate that the recovery from a mivacurium-induced neuromuscular blockade is not influenced by the rate of decay of its plasma concentration in patients with genotypically normal plasma cholinesterase.     

Membranes in Artificial Organs

Abstract: Membrane processes play a pivotal and enabling role in modern replacement therapy for acute and chronic organ failure and in the management of immunologic diseases. In fact, virtually all contemporary extracorporeal blood purification methods employ membrane devices, and the next generation of artificial organs and tissue engineering therapies are almost certain to be similarly grounded in membrane technology. In this short essay, we comment on the similarities and differences among synthetic membranes and their natural counterparts and also provide a critical overview of the demographics and technology of hemodialysis, hemofiltration, apheresis, oxygenation, and emerging membrane technologies and applications.     

Reduction of Plasma Fibrinogen, Immunoglobulin G, and Immunoglobulin M Concentrations by Immunoadsorption Therapy with Tryptophan and Phenylalanine Adsorbents

Abstract Immunoadsorption (1A) therapy with tryptophan (TR-350) or phenylalanine (PH-350) adsorbents has been used to reduce the concentration of serum antibodies in human lymphocyte antigen (HLA)-immunized patients. Other forms of plasma purification have been reported to reduce the level of fibrinogen, which affects the blood properties. In this study we investigated the effects of IA therapy using both adsorbents on plasma fibrinogen and immunoglobulins G and M in 13 patients (8 patients were treated with TR-350, and 5 patients were treated with PH-350). During each session 1 plasma volume (2.8 ± 0.4 L of plasma) was processed through the immunocolumn and then returned to the patient together with the blood cells. Compared with the pretreatment values, the plasma fibrinogen, IgG, and IgM concentrations were significantly reduced after IA therapy (p < 0.01 for TR-350; p < 0.04 for PH-350). There was a positive correlation between the degree of reduction of plasma proteins and the number of IA treatments given. A nonpara-metric test (Wilcoxon's signed-rank test or the Mann-Whitney test) was used for statistical analysis. We conclude from our study that IA therapy effectively lowers the plasma levels of fibrinogen, IgG, and IgM and thus can be considered a valuable alternative to other blood purification methods.     

Dilemma of Membrane Biocompatibility and Reuse

Abstract: Numerous articles have been published on the multiple use of dialyzers and on the effect of different reprocessing chemicals and techniques on the dialyzer biocompatibility and performance. The results often appear contradictory, especially those comparing standard biocompatibility parameters. Despite this confusion, a discerning review of the published works allows certain limited conclusions to be drawn. Reprocessing of used hemodialyzers changes the biocompatibility profile of a dialyzer as defined by the parameters complement activation. leukopenia, and cytokine release. The effect of reprocessing depends on the chemicals and reprocessing technique applied and also on the type of membrane polymer being subjected to the reprocessing procedure. Reports of pyrogenic reactions indicate that the flux of the membrane also influences how suitable it is for safe reuse. An increased risk of allergic and pyrogenic reactions appears to be associated with dialyzer reuse. Furthermore, there has been a lack of investigations into the immunologic effect of the layer of adsorbed and chemically altered proteins that remains on the inner surface of reprocessed dialyzers. We conclude that the clinical benefit of dialyzer reuse cannot be generally accepted from a biocompatibility point of view.     

The analgesic effect of racemic ketamine in patients with chronic ischemic pain due to lower extremity arteriosclerosis obliterans

Background : Ketamine in sub-dissociative doses has been shown to have analgesic and phantom-Limb pain, where conventional treatment has often failed. Chronic ischemic pain due to lower extremity arteriosclerosis obliterans often responds poorly to analgesics, and the pain-generating mechanisms are not well understood.
Methods : Eight patients with rest pain in the lower extremity due to arteriosclerosis obliterans were given sub-dissociative doses of 0.15, 0.30, or 0.45 mg/kg racemic ketamine and morphine 10 mg as a 5-min infusion on four separate days in a cross-over, double-blind, randomised protocol. Plasma levels of (S)- and (R)-ketamine and their nor-metabolites were analysed with an enantioselective high-performance liquid chromatography (HPLC) method. Pain levels were evaluated with a visual analogue scale (VAS).
Results : Individual pain levels were highly variable during and after all the infusions but the pooled pain levels showed a dose-dependent analgesic effect of ketamine with a transient but complete pain relief in all patients at the highest dose (0.45 mg/ kg). Side-effects, mainly disturbed cognition and perception, were pronounced and dose-dependent. Morphine 10 mg had an analgesic peak at 20 min and 5/8 patients had complete pain relief. The remaining 3 patients also had high baseline pain scores, indicating a higher analgesic potency for the 0.30 and 0.45 mg/ kg ketamine doses than for morphine 10 mg.
Conclusion : We have demonstrated a potent dose-dependent analgesic effect of racemic ketamine in clinical ischemic pain. Due to a narrow therapeutic window, this analgesic effect is probably best utilised in combination with other analgesics.     

Intravenous endotoxin does not increase tissue extravasation of albumin in rats

Background : It is unclear whether activation of the inducible nitric oxide synthase (iNOS) increases or decreases the extravasation of plasma.
Methods : Chloralose anaesthetised male Wistar rats received E. coli lipopolysacharide (LPS), 3 mg kg^-1 i.v., or the corresponding volume of saline, 3 or 5 h before the end of the experiment. Mean arterial pressure (MAP) and heart rate (HR) were recorded. Tissue clearance of radio-labelled albumin, during the last 2 h of each experiment, was determined by a double-isotope method. In separate animals, the serum concentration of nitrite and nitrate was determined, 5 h after LPS or the solvent.
Main Results : LPS initially decreased MAP and lastingly increased HR. In the 3-h LPS animals (n=8), tissue plasma clearance was lower in the heart and calf muscle and increased only in diaphragm, compared to corresponding control animals (n=8). In the 5-h LPS rats, clearance was lowered (n=8) in the entire gastrointestinal tract and in testes, compared to controls (n=8). The serum nitrite/nitrate concentration was higher in animals given LPS (n=6) than in controls (n=6).
Conclusion : After LPS, tissue clearance of albumin was not increased in any major tissue, in spite of increased serum levels of NO end products. Apparently, after activation of iNOS, the augmented release of NO is not necessarily associated with increased albumin extravasation.     

The multiply injured child

Blunt trauma is the principal cause of childhood death in many developed countries. This review outlines the differences between adults and children with respect to resuscitation and treatment of orthopaedic injuries in a child with polytrauma. Recent advances in techniques of fracture stabilization are reported.     

Adrenaline markedly improves thoracic epidural analgesia produced by a low-dose infusion of bupivacaine, fentanyl and adrenaline after major surgery: A randomised, double-blind, cross-over study with and without adrenaline

Background: Basic pharmacological research indicates that there are synergistic antinociceptive effects at the spinal cord level between adrenaline, fentanyl and bupivacaine. Our clinical experience with such a mixture in a thoracic epidural infusion after major surgery confirms this. The objectives of the present study were to evaluate the effects on postoperative pain intensity, pain relief and side effects when removing adrenaline from this triple epidural mixture. Methods: A prospective, randomised, double-blind, cross-over study was carried out in 24 patients after major thoracic or abdominal surgery. Patients with only mild pain when coughing during a titrated thoracic epidural infusion of about 10 ml · h^?1 of bupivacaine 1 mg · ml^?1, fentanyl 2 μg · ml^?1, and adrenaline 2 μg · ml^?1 were included. On the 1^st and 2^nd postoperative days each patient was given a double-blind epidural infusion, at the same rate, with or without adrenaline. The effect was observed for 4 h or until pain when coughing became unacceptable in spite of a rescue analgesic procedure. Rescue analgesia consisted of up to two epidural bolus injections per hour and i.v. morphine if necessary. All patients received rectal paracetamol 1 g, every 8 h. Fentanyl serum concentrations were measured with a radioimmunoassay technique at the start and end of each study period. Main outcome measures were extent of sensory blockade and pain intensity at rest and when coughing, evaluated by a visual analogue scale, a verbal categorical rating scale, the Prince Henry Hospital pain score, and an overall quality of pain relief score. Results: The number of hypaesthetic dermatomal segments decreased (P <0.001) and pain intensity at rest and when coughing increased (P <0.001) when adrenaline was omitted from the triple epidural mixture. This change started within the first hour after removing adrenaline. After 3 h pain intensity when coughing had increased to unacceptable levels in spite of rescue analgesia (epidural bolus injections and i.v. morphine). Within 15–20 min after restarting the triple epidural mixture with adrenaline, pain intensity was again reduced to mild pain when coughing. Serum concentration of fentanyl doubled from 0.22 to 0.45 ng · ml^?1 (P <0.01), and there was more sedation during the period without adrenaline. Conclusions: Adrenaline increases sensory block and improves the pain-relieving effect of a mixture of bupivacaine and fentanyl infused epidurally at a thoracic level after major thoracic or abdominal surgery. Serum fentanyl concentrations doubled and sedation increased when adrenaline was removed from the epidural infusion, indicating more rapid vascular absorption and systemic effects of fentanyl.     

Utilisation des médicaments prokinétiques en réanimation : indications et limites ?

Enteral feeding is often limited by gastric and intestinal motility disturbances in critically ill patients, particularly in patients with shock. So, promotility agents are frequently used to improve tolerance to enteral nutrition. This review summaries the pathophysiology, presents the available pharmacological strategies, the clinical data, the counter-indications and the principal limits. The clinical data are poor. No study demonstrates a positive effect on clinical outcomes. Metoclopramide and erythromycin seems to be the more effective. Considering the risk of antibiotic resistance, the first line use of erythromycin should be avoided in favor of metoclopramide.