轻链沉积病肾损害的诊断与治疗

轻链沉积病(LCDD)为单克隆免疫球蛋白轻链在肾脏、心脏、肝脏等组织的沉积。LCDD肾损害起病时多伴有慢性肾功能不全。典型的LCDD肾损害有相对特殊的临床表现,血、尿蛋白电泳及游离轻链定量有助于诊断,确诊需行肾组织病理学检查,包括光镜、荧光显微镜及电镜等检查。LCDD肾损害的治疗应综合考虑B细胞增殖程度和单克隆免疫球蛋白对肾功能造成的损害。应积极控制B细胞增殖,但治疗时应选择肾毒性较小的药物如硼替佐米,必要时改用大剂量马法兰＋周围血干细胞移植(HDM/ASCT)方案。     

肾脏淀粉样变性的临床病理分析

目的：探讨肾脏淀粉样变性病（amyloidosis,AL）的临床病理特点、诊断及鉴别诊断。方法回顾性分析9例肾脏淀粉样变性病患者的临床表现,并对其肾活检组织进行光镜、特殊染色、免疫荧光、免疫组化及超微结构观察。同时对患者进行随访获取预后信息。结果9例肾脏淀粉样变性病患者的临床上主要表现为肾病综合征伴进行性肾功能不全并逐渐恶化。肾活检组织光镜观察,早期淀粉样变光镜表现轻微,可有系膜轻度增生或基底膜空泡变性及轻度增厚,PASM染色可见节段性睫毛状结构;后期,肾小球系膜区明显增宽、基底膜增厚,毛细血管腔闭塞,呈无细胞结节硬化状态。免疫荧光表现不一,部分病例全部阴性,部分表现免疫球蛋白及补体沿系膜区或毛细血管壁不同程度的沉积。刚果红染色呈砖红色,甲基紫染色呈紫红色。免疫组化显示,5例来源于轻链λ,1例来源于轻链κ,全阴性者有3例。电镜观察下,肾小球毛细血管基底膜部分节段无明显病变,部分节段不规则增厚,肾小球基底膜外侧和（或）内皮下可见淀粉样纤维沉积;系膜轻、中度无细胞性增生,其内可见不规则排列淀粉样纤维沉积,直径8~10 nm,无分支,僵硬,排列紊乱。足突大部分融合,肾间质纤维化,其内亦可见淀粉样纤维沉积。结论肾脏淀粉样变性多见于中老年,根据光镜的典型病理学改变,并结合刚果红和甲基紫染色,可明确诊断。电镜检查是早期诊断肾淀粉样变的重要手段。     

经补体活化途径及电镜校正诊断的Ⅰ型膜增生性肾炎一例

<正>Ⅰ型膜增生性肾炎(membranoproliferative glomerulonephritis,MPGN)属于免疫复合物介导的肾小球疾病,以循环免疫复合物介导为主,经典途径激活补体在发病机制中起重要作用[1]。其诊断依靠临床特点,肾活检组织光镜、免疫荧光和电镜的综合结果,而有时电镜超微病理观察起决定性作用[2]。2013年9月我院收治1例以肾病综合征、肉眼血尿伴肾功能损害,及补体C3、C4下降为主要临床特征的患者。入院后肾活检经光镜及免疫荧光检查拟诊断为"继发性毛细血管     

24例肾淀粉样变性病的临床与病理分析

目的:探讨肾淀粉样变性病的临床与病理特点。方法:回顾性分析我院2008年1月~2015年12月收治的24例经肾活检明确诊断为肾淀粉样变性病患者的临床病理表现,并根据肾组织中淀粉样蛋白A、轻链蛋白K、λ沉积情况进行分型。结果:24例肾淀粉样变性病患者中男15例,女9例;年龄47岁~81岁,平均(65.4±14.2)岁;慢性肾炎型表现为尿蛋白定量在1.0~3.5 g/d者7例,占29.2%;肾病综合征17例,占70.8%。此外,镜下血尿阳性占29.1%,血肌酐2 mg/dl占8.33%。对男女两组患者进行对比分析,两组血肌酐、尿蛋白定量两项指标差异有统计学意义(P0.05)。依据免疫组化进行淀粉样变病理分型,其中AL-λ型19例,AL-κ型3例,AA型1例,未分型1例。结论:肾淀粉样变性病好发于中老年,临床表现缺乏特异性,老年肾病综合征患者伴血压下降、多系统受累应高度怀疑本病。肾活检病理检查对早期诊断极为重要,免疫组化有助于肾淀粉样变性病的病理分型诊断。     

44例肾淀粉样变患者临床分析

目的：分析本中心肾淀粉样变性患者临床病理特点及其相关性,以指导及提高早期诊断水平.方法：回顾性分析2001年8月-2012年10月在本中心住院并行肾活检确诊为肾淀粉样变的44例患者的临床病理资料.对男女亚组进行对比分析及相关性分析.结果：44例肾淀粉样变患者中男31例,女13例;平均年龄（58.02±8.86）岁;81.82%的患者临床表现为肾病综合征,镜下血尿≥（＋）占18.18%,2例确诊为多发性骨髓瘤（MM）;3例伴有高血压;合并有乙肝病毒携带或者慢性乙肝者占25%.肾病理上血管刚果红染色阳性者占83.2%,20例患者电镜下可见细纤维丝.对男女两组患者进行对比分析,两组在血肌酐、尿蛋白定量、尿轻链κ、血白细胞上差异有统计学意义（P〈0.05）.结论：肾淀粉样变多见于中老年人,临床多表现为肾病综合征,血尿少见;较多合并有心电图异常及肝脾肿大,对可疑患者尽早行肾活检.男性患者尿蛋白及尿轻链κ多于女性.     

血清游离轻链比值测定对鉴别骨髓瘤肾病致尿毒症的指导意义

目的探讨血清游离轻链比值（serum free light chain ratio, rFLC）测定对鉴别骨髓瘤肾病致尿毒症的指导意义。方法采用免疫比浊法测定39例初诊为尿毒症患者的血清游离轻链值,根据其临床诊断分为多发性骨髓瘤致尿毒症组12例;非多发性骨髓瘤致尿毒症组27例;比较2组．c血清游离轻链（κ-sFLC）、x血清游离轻链（κ-sFLC）及rFLC的差异,并分析其相关性。结果多发性骨髓瘤致尿毒症患者κ-sFLC、λ—sFLC高于正常范围的比例分别为83．3％和66．6％;非多发性骨髓瘤致尿毒症患者k-sFLC、λ-sFLC高于正常范围的比例分别为96．3％和96．3％,无统计学差异（P〉0．05）;多发性骨髓瘤致尿毒症组rFLC均不在正常范围内,非多发性骨髓瘤致尿毒症组rFLC均在正常范围内,具有统计学差异（P〈0．05）。多发性骨髓瘤致尿毒症组κsFLC与λ-sFLC无显著相关性（P〉0．05）;非多发性骨髓瘤致尿毒症组κ-sFLC与λ-sFLC呈正相关（P〈0.01,r=0．675）。结论rFLC可以反映κsFLC和λsFLC是否是单克隆性增高,可以作为鉴别骨髓瘤肾病所致尿毒症的可靠指标。     

淀粉样管型肾病的临床病理特征分析

目的 探讨轻链淀粉样管型肾病（light chain amyloid casts,LCAC）的临床病理学特征,加深对LCAC的认识。方法 回顾2018年1月至2021年6月在广州金域医学检验中心肾脏病理诊断为LCAC的患者,将患者分为单纯LCAC(pure light chain amyloid casts,I-LCAC)组和LCAC合并轻链淀粉样变性肾病（lightchainamyloidcastswithlightchainamyloidnephropathy,LCAC&AL）组,所有患者均进行了光镜、免疫荧光、电镜和免疫电镜检查,对两组患者的肾脏病理进行半定量评分进行分析,评估两组患者的临床病理学特征。结果 同期诊断为轻链管型肾病（light chain cast nephropathy, LCCN）的患者共131例,其中15例诊断为LCAC(11.5%),包括ILCAC组10例和LCAC&AL组5例;LCAC有9例临床确诊为多发性骨髓瘤,其中I-LCAC组7例,LCAC&AL组2例,两组差异无统计学意义;与LCAC&AL组相比,I-LCAC组患者...     

几种重要肾小球肾炎的免疫组化诊断与鉴别诊断及其进展

肾活检病理诊断的特殊性在于它由光镜、免疫病理及超微病理三部分组成.三种手段相辅相成,有时缺一不可.免疫荧光或免疫组化技术对肾脏疾病的诊断及其分类具有重要作用,因而在肾活检病理诊断中占有极为重要的地位.许多肾病的诊断通常需要证实有无免疫球蛋白、轻链或补体成份的特征性沉积,如膜性肾病、IgA肾病、抗肾小球基膜肾炎、轻链肾病以及定义不明确或有争议的疾病如免疫触须样肾小球肾炎、IgM肾病和C1q肾病等.     

免疫细胞化学法检测尿足细胞的临床应用

目的：免疫荧光细胞化学和免疫酶细胞化学两种方法检测尿足细胞的比较，以促其临床推广应用。方法：尿标本均为我科住院患者的肾活检日新鲜晨尿，采用抗人足细胞标记蛋白Podocalxin（PCX）单克隆抗体进行尿沉渣免疫荧光细胞化学和免疫酶细胞化学染色。14例患者均经肾活检，肾组织由光镜、免疫荧光和电镜检查做出病理诊断。结果：（1）14份尿标本应用免疫荧光细胞化学和免疫酶细胞化学方法均可检测到足细胞。（2）同一份尿沉渣采用免疫荧光细胞化学法检测足细胞均数为（16、7±15、1）／HP，而免疫酶细胞化学法检测足细胞均数为（26，1±24、3）／20HP，两组比较有统计学意义（P〈0、05）；但两种方法所测足细胞数之间有很好的相关性（r=0、969）。结论：免疫荧光细胞化学和免疫酶细胞化学两种方法检测尿足细胞，前者较简便、镜下易辨认，后者设备简单、标本可保存。     

伴有免疫复合物沉积的ANCA相关性小血管炎患者临床及肾脏病理分析

目的：探讨有免疫复合物沉积的ANCA相关性小血管炎（AASV）患者临床及病理特点。方法：回顾性地分析近5年诊断明确并行肾活检的27例患者,根据免疫荧光及电镜分为有免疫复合物沉积组和少免疫复合物沉积组,均使用激素及免疫抑制剂治疗,比较两组的临床、病理特点及疗效、预后。结果：有免疫复合物沉积组14例,少免疫复合物沉积组13例。两组在年龄、性别、ANCA类型、起病至肾活检时间,发热、乏力等非特异性表现及肾外器官受累方面差异均无统计学意义。在血尿、高血压及血肌酐方面亦无明显差异,但有免疫复合物沉积组尿蛋白明显高于后者,差异有统计学意义。对激素及免疫抑制治疗的疗效及预后可能更差,但差异无统计学意义。在病理类型方面,两组均为新月体性肾炎,但有免疫复合物沉积组可合并IgA肾病和膜性肾病。结论：肾脏有免疫复合物沉积提示更多的尿蛋白,可能更差的疗效及预后,病理类型上在新月体性肾炎基础上合并IgA肾病和膜性肾病。     

Vasopressor hormone response following mesenteric traction during major abdominal surgery

Background : We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI₂) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. Methods : In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGFlα (stabile metabolite of PGI₂), TXB₂ (stabile metabolite of thromboxane A₂) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. Results : Following MT, arterial hypotension occurred along with a substantial PGI₂ release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF_1α (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P=0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB² (164 (87) vs. 58 (1) ng/L, P=0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P=0.001), AVP (41 ± (18) vs. 12 (7) ng/L, P=0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. Conclusion : Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI₂ release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A₂, presumably contributing to hemodynamic stability within 30 min after MT.     

A comparison of the inhibitory effects of four volatile anaesthetics on the metabolism of chlorzoxazone, a substrate for CYP2E1, in rabbits

Background: Halothane inhibits in vitro and in vivo activity of cytochrome P-450 (CYP) 2E1. There are several fluorinated volatile anaesthetics besides halothane, and most of them are defluorinated by CYP2E1. It is unclear whether other fluorinated anaesthetics inhibit the in vivo activity of CYP2E1.
Methods: We compared the inhibitory effects of therapeutic concentrations of four inhalational anaesthetics, halothane, enflurane, isoflurane, and sevoflurane, on chlorzoxazone metabolism in rabbits receiving artificial ventilation.
Results: All four inhalational anaesthetics decreased arterial blood pressure and increased plasma chlorzoxazone concentration. However, no significant differences in the plasma chlorzoxazone concentration were found between the four anaesthetics. The estimated chlorzoxazone clearance increased after beginning inhalation with all four agents, but no significant difference in clearance was noted between agents.
Conclusions: At therapeutic concentrations, the in vivo inhibitory effect on chlorzoxazone metabolism was similar for all four inhalational anaesthetics examined, even though their chemical characteristics and extent of hepatic metabolism differ considerably.     

A Teaspoon Pump for Pumping Blood with High Hydraulic Efficiency and Low Hemolysis Potential

Abstract: Virtually all blood pumps contain some kind of rubbing, sliding, closely moving machinery surfaces that are exposed to the blood being pumped. These valves, internal bearings, magnetic bearing position sensors, and shaft seals cause most of the problems with blood pumps. The original teaspoon pump design prevented the rubbing, sliding machinery surfaces from contacting the blood. However, the hydraulic efficiency was low because the blood was able to "slip around" the rotating impeller so that the blood itself never rotated fast enough to develop adequate pressure. An improved teaspoon blood pump has been designed and tested and has shown acceptable hydraulic performance and low hemolysis potential. The new pump uses a nonrotating "swinging" hose as the pump impeller. The fluid enters the pump through the center of the swinging hose; therefore, there can be no fluid slip between the revolving blood and the revolving impeller. The new pump uses an impeller that is comparable to a flexible garden hose. If the free end of the hose were swung around in a circle like half of a jump rope, the fluid inside the hose would rotate and develop pressure even though the hose impeller itself did not "rotate"; therefore, no rotating shaft seal or internal bearings are required.     

Microspheres Based Detoxification System: A New Method in Convective Blood Purification

Abstract: A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.     

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.     

Tissue perfusion in relation to cardiac output during continuous positive-pressure ventilation and administration of propranolol or verapamil

Background : Our objective was to determine whether administration of propranolol or verapamil modifies the hemodynamic adaptation to continuous positive-pressure ventilation (CPPV), in particular the regional distribution of cardiac output (CO).
Methods : General hemodynamics and regional blood flows assessed by microsphere technique (15 (μm) were recorded in 16 anesthetized pigs during spontaneous breathing (SB) and CPPV with 8 cm H₂O end-expiratory pressure (CPPV8) before and after intravenous administration of propranolol (0.3 mg · kg⁻¹ followed by 0.15 mg · kg⁻¹ · h⁻¹, n=8) or verapamil (0.1 mg · kg⁻¹ followed by 0.3 mg · kg⁻¹ · h⁻¹, n=8).
Results : CPPV8 depressed CO by 25% without shifts in its relative distribution with the exception of a noteworthy increase in adrenal perfusion. Propranolol increased arterial blood pressure, and due to a fall in heart rate, CO dropped by 25%. The kidneys and, to a lesser extent, the splanchic region and central nervous system received increased fractions of the remaining CO at the expense of skeletal muscle flow. Similar patterns were seen during SB and CPPV8 such that the combination of propranolol and CPPV8 depressed CO by 50%. The circulatory effects of verapamil were less evident but myocardial perfusion tended to increase.
Conclusions : The combination of propranolol or verapamil with CPPV does not result in any specific hemodynamic interaction in anesthetized pigs, except that the combined effect of propranolol and CPPV may severely reduce CO.     

Volatile anaesthetics reduce adhesion of blood platelets under low-flow conditions in the coronary system of isolated guinea pig hearts

Background : Inhibitory effects of volatile anaesthetics on platelet aggregation have been demonstrated in several studies. However, the influence of volatile anaesthetics on intracoronary platelet adhesion has not been elucidated so far.
Methods : Isolated hearts of guinea pigs were perfused with buffer in the absence or presence of volatile anaesthetics (0.5 and 1 MAC) at constant coronary flow rates of 5 ml/min for 25 min, then 1 ml/min for 30 min and again 5 ml/min for 10 min. Before, during and after low-flow perfusion, a bolus of human platelets was applied into the coronary system. To simulate thrombogenic conditions, 0.3 U/ml human thrombin was infused during low-flow perfusion and reperfusion. The number of platelets sequestered to the endothelium was calculated from the difference between coronary in- and output of platelets. The myocardial production of lactate and consumption of pyruvate and coronary perfusion pressure were also determined.
Results : At a flow rate of 5 ml/min only about 3% of the applied platelets did not emerge from the coronary system, in any group. In contrast, 13.1±1.2% (mean±SEM) of infused platelets became adherent in low-flow perfusion in the control group without anaesthetic. The adherence was reduced with each 1 MAC isoflurane (to 6.2±1.2%), sevoflurane (to 4.4±0.9%) or halothane (to 3.2±1.5%) (each P <0.05 vs. control). Volatile anaesthetic, 0.5 MAC, did not inhibit platelet adhesion to a statistically significant extent in any case. Perfusion pressure and metabolic parameters were not statistically different between the control and the hearts exposed to anaesthetics.
Conclusion : Volatile anaesthetics in a concentration of 1 MAC can reduce the adhesion of platelets in the coronary system under reduced flow conditions. This action does not arise from vasodilation or inhibition of ischaemic stress.     

Bariatric Surgery in Some "Central and East-European (former Eastern bloc)"Countries - Current Status and Prediction for the Next Millennium

Background: Obesity is increasing globallly, including in the formerly "Eastern Bloc" countries. Methods: A survey was made of obesity and bariatric surgery. Results: In the 8 East and Central European countries studied, with total population 300 million, roughly 43% of the population was overweight (BMI 25-30), 23% obese (BMI > 30), with about 15 million people morbidly obese (BMI > 40). From 0-10 morbidly obese individuals/100,000/year undergo bariatric surgery. Conclusion: Most countries were found to provide inadequate treatment for obesity.The majority of the morbidly obese are not treated effectively. However, health-care awareness of obesity and bariatric surgeons are slowly increasing.     

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.