显微镜下多血管炎3例伴文献复习

目的 分析显微镜下多血管炎(MPA)的临床特点,提高对MPA的认识,以提高诊断水平.方法 回顾性分析我科确诊的3例MPA患者的临床表现、实验室检查、病理改变、治疗及预后.结果 3例患者均以肺部症状就诊,伴肾脏受累,MPO-ANCA均阳性.结论 MPA临床表现无特异性,大多具有多脏器受累的特点,以肾脏及肺脏病变最为多见,易误诊,抗中性粒细胞胞质抗体(ANCA)对MPA的诊断有重要价值.     

显微镜下型多血管炎肾损害23例临床病理分析

目的了解显微镜下型多血管炎（MPA）肾损害患者临床和病理特征.方法对23例MPA的临床、病理改变进行分析归纳,并将抗中性粒细胞胞质抗体（ANCA）（＋）和ANCA（-）的MPA患者进行比较.结果MPA患者多见于老年男性,肾外表现除发热、体重下降、纳差非特异症状外,还多见肺损害、浆膜炎、关节炎、肌痛等.65.2%的患者ANCA（＋）.肾脏表现均有血尿、蛋白尿,表现为不同程度的肾功能损害.病理上显示23例患者均有肾小球新月体形成,新月体以纤维性为主,半数以上患者见袢坏死及间质血管炎.结论MPA患者除肾脏功能损害外,常伴肾外表现,而ANCA（＋）与ANCA（-）组在临床表现、肾脏病理方面差异有统计学意义.     

如何提高小血管炎肾损害的远期预后

微型多血管炎(Microscopie polyangiitis,MPA)、Wegener肉芽肿等系统性小血管炎累及肾脏以及局限于肾脏的血管炎(称为renal-limited MPA)是临床常见的原发性肾小血管炎,因多数患者血清抗中性粒细胞胞浆抗体(ANCA)阳性而称为ANCA相关性血管炎.     

以肺部病变为主要表现的ANCA相关性血管炎10例临床分析

目的从呼吸系统疾病的角度分析和认识ANCA相关性血管炎(ANCA-associated Vasculitis,AAV)。方法回顾性分析我院确诊的10例以呼吸系统病变为主要表现的AAV患者的临床资料,对患者的临床表现、实验室检查、影像学表现以及其他特殊检查结果进行汇总分析,采用五因子评分系统评估预后。结果本组患者显微镜下多血管炎(microscopic polyangiitis,MPA)7例,肉芽肿性多血管炎(granulomatosis with polyangiitis,GPA)2例,嗜酸性肉芽肿性血管炎(eosinophilic granulomatosis with polyangiitis,EGPA)1例,男性3例,女性7例。咳嗽咳痰咯血及呼吸困难是AAV最常见的呼吸系统症状,部分患者合并其他系统特别是肾脏累及。实验室检查MPA均有p ANCA和MPO-ANCA阳性,GPA和EGPA患者有c ANCA和PR3-ANCA阳性,7例患者有CRP升高(82.18±48.67mg/L),10例患者均有血沉升高(62.9±13.5mm/h);仅有4例患者出现肌酐轻度升高(139±29.3umol/L),3例患者淋巴细胞总数降低,提示继发感染风险大,预后欠佳。影像学表现多表现为双肺磨玻璃斑片影、间质改变以及蜂窝肺表现,对诊断具有提示作用。肺功能检查表现为限制性通气功能障碍,部分患者出现肺动脉高压。结论肺部是AAV的常见累及器官,部分患者以肺部病变为主要表现,呼吸科医生应加强对AAV的认识,提高诊断率,减少误诊和漏诊。     

抗中性粒细胞胞浆抗体相关血管炎肾损害的临床病理分析

目的:分析抗中性粒细胞胞浆抗体(ANCA)相关血管炎(AAV)伴肾损害患者的临床和病理特征。方法:112例临床诊断为AAV,血清ANCA阳性(间接免疫荧光和ELISA法),伴有肾损害并均行肾活检的患者。回顾性分析其临床和病理特征,分析肺出血危险因素及ANCA类型与临床病理的联系。结果:(1)一般情况:男女比例1∶1.6,平均起病年龄(46.3±16.8)岁,半数患者在50岁以后发病,病程0.2～192月(中位病程6个月)。98例(87.5%)MPO-ANCA阳性,13例(11.6%)PR3-ANCA阳性,1例MPO-ANCA与PR3-ANCA双阳性。31%伴血清抗内皮细胞抗体阳性(IIF法),2.7%同时合并抗肾小球基膜抗体(IIF法)。临床类型中微型多血管炎(MPA)102例(占91.1%),韦格纳肉芽肿(WG)10例(占8.9%)。(2)临床表现:首发症状依次为全身症状(30.4%)、肾损害(29.5%)、咯血(13.4%)和皮肤关节损害(16%)。肾外脏器受累率依次为肺(50.9%)、上呼吸道(19.6%)、关节(19.6%)、皮肤(18.8%)、浆膜炎(17.9%)、眼(17.9%)、消化道(8.9%)、心脏(6.3%)和神经系统(5.4%),33%伴有血小板减少。(3)肾损害:92%患者伴肾功能不全[SCr平均(428.7±297.0)μmol/L],37.5%需即时肾脏替代治疗。所有患者有镜下血尿,其中1/4有肉眼血尿,大量蛋白尿比例仅21.4%。肾活检病理:92%患者有肾小球新月体形成[平均新月体比例(63.7±27.9)%],52.7%伴毛细血管袢节段坏死,71.4%伴有球性硬化[平均肾小球硬化比例(41.8±27.8)%],均有小管间质纤维化。(4)伴有肺出血组(n=34)与无肺出血组(n=78)比较,前者肾功能损害更重[SCr(556.0±362.4)vs(373.0±245.8)μmol/L,P<0.01],抗内皮细胞抗体(AECA)阳性率高[48.0%vs24.6%,P<0.05],ANCA水平差异无统计学意义[(307.3±374.1)vs(310.2±444.4),P>0.05]。Logistic回归分析发现AECA阳性为肺出血主要风险因素(P<0.05)。结论:本组AAV以MPO-ANCA相关的MPA为主,发病年龄轻,女性比例高;肾功能损害重且病程迁延,表明早期诊断的必要性;AAV肺出血与血清AECA相关。     

抗中性粒细胞胞浆抗体阳性与阴性微型多血管炎的比较

目的比较抗中性粒细胞胞浆抗体(ANCA)阳性(ANCA+ve)与ANCA阴性(ANCA-ve)微型多血管炎(MPA)临床与病理的差异,探讨ANCA与MPA病情及预后的关系.方法31例微型多血管炎(MPA),其中男16例,女15例,同时采用标准间接免疫荧光(IF)和ELISA法检测血清ANCA,根据血清ANCA结果分为ANCA+ve组与ANCA-ve组,比较两组肾脏及肾外脏器损害、肾脏病理及预后.两组患者血管炎活动分数(BVAS1)无差异.结果①血清ANCA31例MPA中19例ANCA阳性(61.3%),其中IF-ANCA阳性者8例,ELISA法ANCA阳性者19例.血清抗-GBM抗体均阴性.②发病年龄及病程ANCA+ve组大于ANCA-ve组,分别为(56±11)岁vs(48.5±16.8)岁(P＜0.05)和(30.2±47.7)月vs(6.5±8.8)月(P＜0.01).ANCA+ve组女性多于男性(男/女8/11),而ANCA-ve组男性多见(男/女8/4).③ANCA+ve组需透析病例数及活检时SCr水平(588±334)μmol/L高于ANCA-ve(487±284)μmol/L(P＜0.05),贫血程度更为严重,Hb(78.9±16.2)g/Lvs(95.5±22.0)g/L(P＜0.01).肾活检显示ANCA+ve组新月体比例显著高于ANCA-ve组(61.7±33.2)%vs(33.4±32.8)%(P＜0.01),ANCA-ve组细胞性新月体所占比例高于ANCA+ve组.两组袢坏死、全球硬化、间质血管炎及酸性粒细胞浸润程度相似.④ANCA+ve组伴有2个以上肾外脏器受累比例高于ANCA-ve组(63.2%vs31.3%),肺损害较重,咯血(42.1%)及严重肺出血(15.8%)患者均见于ANCA+ve组.ANCA+ve组消化道出血及眼部受累多见,而皮肤损害ANCA-ve组发生率高于ANCA+ve组(41.7%vs15.8%).⑤ANCA-veMPA预后差.两组治疗方法相似,但治疗后ANCA+ve组仅1例肾功能恢复正常,绝大多数患者需维持透析或处于CRF,5例死亡,而ANCA-ve组3例需要维持性透析,4例肾功能恢复正常,无一例死亡,其余病例肾功能均显著改善.结论血清ANCA阳性与ANCA阴性MPA无论在临床表现、肾脏病理及预后方面均存在一定差异,临床应分别对待.造成这种差异的机制有待进一步研究.     

丙基硫氧嘧啶相关血管炎肾损害的临床病理特征及转归

目的:回顾性分析丙基硫氧嘧啶(PTU)相关ANCA血管炎伴肾脏损害患者临床、病理特征及转归.方法:因Graves病或自身免疫性甲状腺炎引起甲状腺功能亢进,服用PTU后出现血清ANCA阳性伴肾脏损害患者12例[女性11例,男性1例,平均年龄(32.4±13.8)岁],均行肾活检病理检查和随访.回顾性分析患者的临床病理特征和转归. 结果:12例患者服用PTU 2～264月(中位时间42月),肾脏病程(11.5±20.1)月,ANCA类型均为P-ANCA,其中11例为MPO-ANCA阳性,1例MPO-/PR3-ANCA双阳性.临床均表现血尿(其中5例肉眼血尿)及蛋白尿[(1.9±1.6g/24h)],7例(58.3%)存在肾功能不全[SCr(282.88±335.92)μmol/L],其中3例人院时即需要肾脏替代治疗.肾活检病理10例为寡免疫复合物节段坏死性肾炎伴新月体形成,2例为节段坏死性肾炎伴膜性病变.治疗上均停用PTU并接受免疫抑制治疗,随访3-60月(中位时间19月),1例进入终末期肾衰,1例SCr倍增,2例转为慢性肾功能不全,8例完全缓解(肾功能正常,尿检阴性).血清ANCA 2例转阴,9例滴度下降,1例无变化.3例肾血管炎复发伴血清ANCA滴度升高. 结论:本组PTU相关血管炎肾功能损害严重,病理改变除与ANCA相关的肾血管炎外,还合并膜性病变,预后不佳,停用PTU后ANCA持续阳性且滴度升高与复发相关,表明对ANCA水平升高者需维持免疫抑制治疗.     

ANCA相关性血管炎肺部表现

目的 研究抗中性粒细胞胞浆抗体(ANCA)相关性血管炎(AASV)在肺部疾病的临床表现及特点.方法 回顾性分析2007年1月至2011年4月于吉林大学第二医院确诊为AASV的30例住院患者肺部病变的临床资料.结果 30例AASV患者发病年龄24～77岁,其中女18例,男12例.30例AASV患者中Wegener肉芽肿(WG)8例,显微镜下多血管炎(MPA) 22例,无变应性肉芽肿血管炎(CSS).结论 所有年龄段均有可能患AASV,MPA的发病率大约是WG的3倍,MPA患病率较多,可能是我国AASV的特点之一.WG患者较MPA患者更易出现呼吸系统症状,MPA患者较WG患者更易累及肾脏,出现肾功改变.影像学表现无特异性改变,但常重于临床表现.AASV肺部病理可表现为特发型肺间质纤维化.随着检验手段的提高,AASV的发病率逐渐增高,其临床表现多变,病变部位广泛,肾脏和肺脏是AASV最易受累的器官.对于长期发热及多器官受损的患者应尽早进行ANCA检查,及时治疗,改善预后.     

老年人显微镜下型多血管炎4例分析

目的 认识老年性显微镜下型多血管炎(MPA)的临床特点。方法 对1999年8月至2003年9月期间，我院确诊的4例MPA患者进行回顾性分析。结果 4例中男3例，女1例，平均72．3岁。临床表现以发热或呼吸道症状起病，可伴有肾损害的表现，易误诊。4例经抗中性粒细胞胞浆抗体(ANCA)阳性确诊，1例行肾活检证实。皮质激素及免疫抑制剂治疗有效。结论 ANCA对MPA的诊断有指导意义，皮质激素及免疫抑制剂治疗有效。     

53例显微镜下多血管炎临床特点及预后

目的回顾性分析显微镜下多血管炎(microscopic polyangiitis,MPA)患者临床资料及对预后进行比较,提高对本病的认识。方法对2008年12月至2014年5月在北京协和医院住院治疗并门诊随诊的MPA患者进行回顾性分析。结果共纳入53例患者,其中男25例,女28例,平均发病年龄(61.7±13.6)岁,平均病程(13.5±20.6)个月。临床表现以肺脏和肾脏受累为主,100%患者存在肾脏受累,其中有32例行肾活检(60.3%),以新月体肾炎Ⅲ型多见(46.8%),无或少有免疫复合物沉积。肺脏以肺泡出血(20.8%)及肺间质病变为主。抗中性粒胞浆抗体(antineutrophil cytoplasmic antibody,ANCA)均为阳性,髓过氧化物酶-ANCA阳性者占92.4%,蛋白酶3-ANCA阳性3.7%,抗核抗体阳性41.5%,抗肾小球基底膜抗体阳性1例,抗心磷脂抗体阳性1例。其中死亡16例,占30.2%。主要的死亡原因包括为肺部感染,肺泡出血,中枢神经系统受累,以及心血管疾病。多在诊断后1~3个月内死亡(81.3%)。结论 MPA患者的受累脏器以肺肾为主,96.2%的患者P-ANCA阳性,30.2%的患者死亡,高龄、低蛋白血症、高疾病活动性为预后不良因素。     

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.     

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.     

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.     

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.