轻链沉积病肾损害的临床和病理分析

目的：了解轻链沉积病(LCDD)肾损害的临床和病理特征。方法：回顾性分析26例经临床和肾活检确诊的LCDD患者的临床和病理改变。结果：26例LCDD患者起病时的平均年龄为49.4岁(27—72岁)，其中男性21例，女性5例。8例确诊为多发性骨髓瘤(MM)，2例伴有浆细胞异常增生，另有16例病因不明。临床表现为急性肾衰3例(11．5％)，慢性肾衰17例(65．4％)，肾病综合征17例(65．4％)，15.4％的患者起病时即需行肾脏替代治疗。实验室检查发现血清和尿液游离κ、λ轻链的阳性率分别为56．5％和91．7％。肾脏病理改变以系膜结节样病变多见，占53．8％，2例表现为膜增生样病变、1例为膜性病变，中—重度小管间质慢性化病变为本组患者较特征性的病变(92．3％)。肾组织中以λ轻链沉积为主者占65．4％(17例)，κ轻链沉积占34．6％(9例)。18例患者行肾组织电子显微镜检查，均显示肾小球和(或)肾小管基膜内(外)侧不规则的纤细颗粒样电子致密物。结论：LCDD患者临床以肾功能不全伴肾病综合征多见，部分患者合并浆细胞增生性疾病。病理以系膜结节样伴严重的小管间质病变为特征。血清、尿液以游离λ轻链增高多见，肾组织中也以λ轻链沉积居多。     

轻链蛋白沉积肾损害12例临床及病理分析

目的 了解轻链蛋白沉积造成肾损害的特点,提高对其发病的认识.方法 回顾分析中国医科大学附属第一医院2006年9月至2007年12月多发性骨髓瘤(MM)和浆细胞肾损害(共9例),以及肾淀粉样变(3例,均为原发、AL)的临床特点与病理特征.结果 MM导致肾功能衰竭4例,肾病综合征2例.浆细胞病3例(1例浆细胞性肾病)中,2例存在肾功能衰竭.大部分MM与浆细胞病血清和(或)尿液中存在kappa、lambda轻链蛋白代谢异常(7/9).3例AL均表现为典型的肾病综合征,肾脏病理均显示lambda轻链蛋白主要沉积在肾小球系膜区、基底膜、肾小管基底膜及小动脉壁.结论 轻链蛋白代谢异常均可引起不同程度的肾脏损伤,产生多样的临床表现.     

多发性骨髓瘤伴肾脏病变患者的临床病理特征和预后

目的:分析多发性骨髓瘤(MM)伴肾脏病变患者的肾脏病理类型、临床特征和预后。方法:收集112例临床诊断MM伴肾脏病变并行肾活检的患者的临床、病理及随访资料。分析肾脏病理类型谱及各病理类型的临床和预后差异。结果:MM伴肾脏病变患者以男性多见,46.4%表现肾病范围蛋白尿,9.8%为肾病综合征,镜下血尿和肾功能损害的比例分别占25.9%和68.8%。依据肾活检病理,肾脏病变分MM相关(75.9%)、MM不相关肾脏病变(18.8%)、两者合并存在(1.8%)及肾脏病理基本正常(3.5%)。MM相关肾脏病变以管型肾病(MCN)、淀粉样变性和单克隆免疫球蛋白沉积病(MIDD)最常见。MCN患者行肾活检时血清肌酐水平最高,肾脏病理示肾小管间质急性病变最重。淀粉样变性患者发病时年龄更大,临床多表现肾病综合征,血中升高的轻链以λ为主。MIDD患者临床肾功能不全及血尿发生率高,血中升高的轻链以κ为主,肾脏病理示肾小管萎缩/间质纤维化慢性病变最重。MM相关肾脏病变患者预后显著差于MM不相关肾脏病变患者。对于前者,AMY组肾存活时间优于MCN和MIDD组,但人中位生存时间无统计学差异。结论:MM伴肾脏病变患者的临床及病理特点各有所不同,预后亦存在差异,肾活检有助于明确肾脏病理类型和程度、判断预后。     

轻链κ/λ比值测定对多发性骨髓瘤诊断的临床应用

目的:探讨血清、尿液轻链含量及κ/λ比值差异在鉴别诊断多发性骨髓瘤(MM)中的临床应用价值。方法:回顾性分析9 120例各类型MM患者血清轻链含量及κ/λ比值数据,并将其中合并肾损伤和无肾损伤MM患者的血、尿轻链及κ/λ比值分别与38例肾病者及100例正常对照者进行比较分析。结果:各类型MM患者所属血清κ型轻链及κ/λ比值显著升高,所属λ型及κ/λ比值显著降低,合并肾损伤检出率约占MM的49.57%,肾损伤MM者血清轻链含量及κ/λ比值均低于无肾损伤MM者(P0.05),但尿液中所属轻链含量显著升高(P0.01)。肾损伤MM患者中同一轻链型多发性骨髓瘤(LCMM)血清与尿液轻链含量及κ/λ比值比较差异有统计学意义(P0.01),而非LCMM血清与尿液轻链含量及κ/λ比值比较差异无统计学意义(P0.05),与肾病者及正常对照者比较差异有统计学意义(P0.01)。结论:血清、尿液轻链含量尤其κ/λ比值差异,对MM的诊断、分型、早期肾损伤及肾病的鉴别诊断有重要的临床应用价值。     

多发性骨髓瘤肾损害发病机制

多发性骨髓瘤(MM)的肾损害是MM最常见和严重的并发症之一,初诊时50％以上患者存在肾功能不全,MM对肾的损害是多因素作用的结果,包括轻链对近曲小管细胞直接毒性,管型肾病,沉积病,淀粉样变性,白介素-6作用等。本文对近年MM肾损害发病机制进展作一总结。     

糖尿病肾病的病理表现

糖尿病肾病 ,又称糖尿病肾小球硬化症 ,为糖尿病的常见微血管并发症 ,1型及 2型糖尿病均可发生。该病主要病变在肾小球及肾脏微动脉 ,肾小球出现以细胞外基质增多为主要特征的的病理表现 ,下面作一详述。1　肉眼大体观察从肾小球高滤过期 (Ｍｏｇｅｎｓｅｎ糖尿病肾损害分期的Ⅰ期 )直至临床糖尿病肾病期 (糖尿病肾损害Ⅳ期) ,糖尿病患者肾脏体积常逐渐增大 ,可增大 >2 0 % ,肾脏体重也随之增加。即使糖尿病肾损害已进展至慢性肾功能不全早期 ,部分患者肾脏体积仍大于正常。2　光学显微镜检查2 .1肾小球病变　糖尿病肾损害Ⅰ期时做病理检查 …     

轻链沉积病患者临床病理特征

目的:阐明轻链沉积病(LCDD)患者的临床病理特征、预后及其相关危险因素。方法:回顾分析LCDD患者的临床、病理及随访资料,应用Kaplan-Meier法分析肾脏存活率,COX回归模型分析预后危险因素。结果:观察45例LCDD患者,肾活检时平均年龄50.8岁,男∶女1.6∶1。11例(24.4%)患者同时确诊多发性骨髓瘤(MM)。患者高血压、贫血、肾功能不全、尿蛋白定量≥3.5 g/24h和镜下血尿的发生率分别为80.0%、95.6%、95.6%、44.4%和82.2%。血清单克隆免疫球蛋白条带阳性者为26.2%,血清轻链κ/λ1.65者占84.4%,31.1%为显著异常(8),33.3%患者补体C3降低。80%的患者组织学改变为肾小球结节样病变,20%为肾小球轻至中度系膜增生,53.3%患者肾小管间质慢性病变重度,77.8%患者光镜下存在轻链相关动脉病变。免疫荧光提示κ轻链沉积占93.3%,沿肾小管和肾小球基膜线样分布,系膜区团块状分布。5例患者失随访,余40例患者平均随访22.1个月,共26例(65.0%)进入ESRD,平均肾脏存活时间为33.8月。单因素和多因素COX回归分析显示,肾活检时血清肌酐(SCr)、尿视黄醇结合蛋白(RBP)是进展至ESRD的重要危险因素,未发现其他临床及病理指标与肾脏预后相关。结论:LCDD多发于中年男性,临床表现高血压、蛋白尿、肾功能不全、贫血,血清轻链比值异常较血清免疫固定电泳是更为敏感的诊断提示。肾小球结节病变、肾小管基膜增厚,电子致密物沿肾小球基膜内侧缘和肾小管基膜外侧缘沉积是主要病理表现。轻链沉积以κ型为主。LCDD患者预后差,SCr、RBP是影响预后的独立危险因素。     

5例伴单克隆免疫球蛋白沉积的增生性肾小球肾炎临床及病理分析

目的 探讨伴单克隆免疫球蛋白沉积的增生性肾小球肾炎(PGNMID)的临床及病理特点。方法 回顾性分析5例PGNMID患者的临床特征及肾脏病理资料。结果 5例PGNMID患者中,男4例,女1例,年龄47～68岁,病程2.5～60.0个月,2例病程超过1年,5例均呈肾病综合征,伴高血压病史,4例镜下血尿,3例肾功能异常。仅1例血清免疫球蛋白游离轻链比率异常。光镜下,5例患者的肾脏均呈膜增生性肾小球肾炎病变;免疫荧光下,PGNMID患者肾小球仅见免疫球蛋白G3和κ轻链沉积;电镜显示PGNMID患者肾脏系膜、内皮下和(或)上皮下颗粒状沉积物。结论 PGNMID患者常出现肾病综合征和肾功能下降,需尽早行肾脏病理检查,以提高PGNMID的诊断率,减少漏诊和误诊。     

多发性骨髓瘤患者肾脏损害的临床分析

多发性骨髓瘤 (ＭＭ)是一种单克隆浆细胞异常增生的恶性疾病 ,多数ＭＭ患者在病程中出现肾损害 ,肾脏病变对ＭＭ的病程和预后具有重要意义。对我院 1978～ 2 0 0 0年收治的12 3例ＭＭ患者的资料进行分析 ,旨在提高对ＭＭ肾病的认识和防治水平。一、资料与方法1 病例 :12 3例ＭＭ ,男 79例 ,女 44例 ,年龄 2 5～ 78岁 ,平均年龄 5 6 3岁。伴持续性蛋白尿、肾病综合征 (ＮＳ)、急性肾功能衰竭 (ＡＲＦ)、慢性肾功能衰竭 (ＣＲＦ)或小管功能障碍者临床诊断为ＭＭ肾病。2 免疫分型及临床分期 :按Ｍ蛋白 ,分为ＩｇＧ、ＩｇＡ、ＩｇＤ、轻链、无…     

强直性脊柱炎相关IgA肾病临床与病理特征

目的：回顾性分析强直性脊柱炎伴IgA肾病的临床病理特点.方法：15例（男12例,女3例）强直性脊柱炎患者,临床有肾脏损害表现,肾活检光镜以系膜增生性病变伴或不伴新月体形成,免疫荧光检查以IgA系膜区沉积为主,回顾分析其临床及病理特征.结果：发生肾损害时强直性脊柱炎病史平均为49.7月（1～240月）,5例患者诊断肾病后才确诊有强直性脊柱炎.13例患者（86.7%）HLA-B27阳性.7例（46.7%）肾损害表现为尿检异常,临床有蛋白尿和镜下血尿;2例（13.3%）以肉眼血尿起病,表现为急性肾炎综合征;6例（40%）起病时表现为慢性肾功能不全.肾活检病理,所有患者均有肾小球系膜和基质增生性病变,8例患者（53.3%）有新月体形成,2例（13.3%）可见节段袢坏死.4例（26.7%）有间质小血管纤维素样坏死,6例（40%）见血管透明变性,3例（20%）间质血管有小血栓形成.10例（66.7%）患者有不同程度的肾小球废弃,4例（26.7%）有半数以上肾小球废弃.8例（53.3%）小管间质中重度纤维化.间质CD68阳性细胞浸润均数为394（188～764）个/mm2.结论：强直性脊柱炎肾脏损害并不少见,临床症状隐匿,容易误诊或漏诊.其肾脏病理改变中突出的血管病变,提示其发病机制不同于原发性IgA肾病,而是继发于强直性脊柱炎.     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.