结缔组织病实验室检查的新进展

抗核抗体是结缔组织病患者血清中存在的具有标志意义的抗体群.抗 ds-DNA 抗体往往存在于系统性红斑狼疮(SLE)患者中。抗 U1核糖核蛋白抗体与 SLE 患者的雷诺氏现象及手指红斑相关.约29%的 SLE 患者还存在抗心肌磷脂抗体。21%的硬皮病患者血清中能检出抗 SC1-70抗体。多发性肌炎(PM)伴肺纤维化的患者中抗J0-1抗体检出率较高。有少数 PM 患者中存在抗7SL RNA 抗体。     

皮肌炎和多发性肌炎伴发肿瘤临床特点及文献回顾

目的比较皮肌炎(DM)、多发性肌炎(PM)合并肿瘤与未合并肿瘤患者的临床特点,寻找可能的危险因素。方法对北京协和医院2007至2012年诊断DM或PM合并肿瘤患者的临床资料进行回顾性分析,对DM或PM合并肿瘤与同期未合并肿瘤患者的临床表现、实验室检查、转归进行比较。检索近10年的炎性肌病合并肿瘤的中文文献,并进行回顾性分析。将文献资料结合本文病例进行描述性分析。结果北京协和医院2007年至2012年DM或PM合并肿瘤患者30例;2007年至2008年DM或PM患者105例,其中5例伴发恶性肿瘤,均为女性,DM4例、重叠综合征1例(DM合并SLE)。DM或PM合并恶性肿瘤患者的肺间质病变发生率低于未合并恶性肿瘤组(P=0.022)。中文文献及本文病例694例患者中,合并鼻咽癌的DM或PM患者最多(30.26%)。结论对于年龄偏大的炎性肌病患者,尤其不伴有肺间质病变及典型抗体的患者,应积极筛查肿瘤。鼻咽癌是DM或PM患者最常见的肿瘤类型,推荐对DM或PM患者行鼻咽部内镜检查提高肿瘤检出率。     

抗Jo-1抗体在多发性肌炎/皮肌炎中的临床研究

目的摇对69例多发性肌炎/皮肌炎(PM/MD)病人抗Jo-1抗体进行检测,了解抗Jo-1抗体阳性与PM/DM临床症状的相关性及对PM/DM的诊断价值。方法应用免疫印迹(IBT)法检测PM/DM病人中的抗Jo-1抗体,对抗Jo-1抗体阳性血清进行免疫双扩散(ID)检测,两者抗Jo-1抗体均阳性者为抗Jo-1抗体阳性组,其他为抗Jo-1抗体阴性组,前瞻性比较PM/DM抗Jo-1抗体阳性组和抗Jo-1抗体阴性组的临床特征。结果本组中抗Jo-1抗体阳性占32%,抗Jo-1抗体阳性患者出现肺间质病变(ILD)、多关节炎/多关节痛、肺部感染和雷诺现象分别为18例(82%)、18例(82%)、17例(77%)、7例(32%);与抗Jo-1抗体阴性组比较,差异有显著性(P<0.05)。另外,在阳性组出现吞咽困难1例(5%),而阴性组为15例(32%),两组相比差异有显著性(P<0郾05)。结论抗Jo-1抗体阳性组PM/DM患者的肺间质病变及多关节炎症状突出,合并肺部感染的概率高,而肌痛或肌无力症状较轻,出现吞咽困难症状概率较低;阴性组出现吞咽困难症状概率较阳性组高。     

成人多发性肌炎或皮肌炎并发慢性假性肠梗阻的临床特点

目的探讨成人多发性肌炎皮肌炎(polymyositisdermatomyositis,PMDM)合并慢性假性肠梗阻(chronic intestinal pseudo-obstruction,CIPO)患者的临床特点及预后,以提高对此类疾病的认识。方法收集北京协和医院2003年11月至2013年10月临床成人PMDM合并CIPO患者的临床资料,回顾性分析及总结临床表现、实验室检查、诊治及转归。结果合并CIPO的成人PM患者2例,DM患者4例,分别占同期住院成人PMDM患者的0.45%(2441)及0.54%(4747)。6例患者男女比例为1∶2,平均年龄(41±15)岁。CIPO均非临床首发症状,发病时间为PMDM诊断后1~10年,部位均位于小肠。83%(56)患者病程中合并出现急性上消化道出血,2例患者经胃镜明确出血部位分别为胃小弯及十二指肠降部,镜下均表现为多发黏膜溃疡出血。6例患者中33%(26)在出现肠梗阻时并无明确肌肉受累表现,67%(46)肌酸激酶、红细胞沉降率及超敏C反应蛋白均处于正常范围。1例患者发病时肌肉活检示小血管炎性病理改变。6例患者中5例接受足量激素(1 mgkg)治疗,2例接受大剂量激素冲击(甲泼尼龙1 gd)联合静脉用人免疫球蛋白治疗,50%(36)患者最终完全缓解。结论成人PMDM患者合并CIPO发病机制尚不清楚,不除外与继发血管炎有关,由于病程中通常合并急性消化道出血,临床处理非常困难,总体死亡率高。早期识别并及时给予大剂量糖皮质激素和免疫抑制剂可能有助于改善预后。     

以急进性肺间质病变为突出表现的无肌炎的皮肌炎

目的了解以急进性肺间质病变为突出表现的临床无肌炎的皮肌炎的临床特点转归和治疗。方法回顾分析本院1998—2005年住院的成人特发性皮肌炎/多发性肌炎(DM/PM)202例,按临床无肌炎的皮肌炎(CADM)、典型DM、PM进行分组,有无合并临床肺间质病变(ILD)进行分层。对随访的145例DM/PM行生存分析和COX回归,分析预后和危险因素。横断面研究用Logistic回归分析ILD相关的预测因子。结果①存在临床ILD是DM/PM预后的最重要危险因素,OR为4．826(95%CI为1．60～14．56．P=0．005)；而亚临床ILD与无ILD的DM/PM生存曲线差异无统计学意义。②CADM、典型DM、PM之合并临床ILD存在不同的病情经过。CADM-ILD呈急进性ILD的临床模式,其6个月存活率仅为40．8%,中位数存活时间仅为10．2个月；而典型的DM-ILD呈现“次急进性”(sub-rapid progressive)的临床模式,5年存活率为54．0%,中位数存活时间为90个月；PM-ILD则为慢性经过,5年和10年存活率分别为72．4%和60．3%,中位数存活时间可达10年,部分DM-ILD和个别PM-ILD患者也可呈现急进性ILD的疾病模式。③Logistic回归显示：四肢近端肌力OR 3．374(95%CI 1．729～6．583,P＜0．01)和血沉OR 1．025 (95%CI 1．002～1．049,P=0．032)与临床ILD呈正相关,血白蛋白水平OR 0．877(95? 0．792～0．970,P= 0．011)则与临床ILD呈负相关。④随访CADM(28例)的病程为3～80个月,其中CADM-ILD超过半数在1年内死亡(12/21)；而病程＞24个月的CADM(8/28例)预后良好。对于无ILD的CADM,主要予中小剂量的激素(＜0．5～1mg·kg~(-1)·d~(-1))治疗,而CADM-ILD则多接受较大剂量的激素(≥1～2mg·kg~(-1)·d~(-1)),且多联用包括硫唑嘌呤、环磷酰胺、环孢素、霉酚酸酯在内的细胞毒药物,但对呈急进性ILD者缺乏疗效。⑤DM/PM随访病例的病死率为24．8%(36/145例),ILD及其并发症作为直接死因的占69．4%(25/36例),与ILD无直接相关的感染占25．0%(9/36例)。纵隔(皮下)气肿,气胸发生率占所有DM/PM-ILD的9．3%(8/86例),也是提示预后不良指征之一。结论ILD是DM/PM的常见并发症,也是最重要危险因素。本文提出了一个新的DM/PM疾病分类模式：即DM/PM是皮损、肌炎和ILD三个维度上相组合的立体疾病谱。CADM是该疾病谱的组成部分,CADM-ILD可呈急进性,是疾病谱中特殊的临床表型。     

自身免疫性疾病并发肺动脉高压83例临床分析

目的分析自身免疫性疾病(AID)合并肺动脉高压的临床特点、诊断以及治疗方法,提高对继发性肺动脉高压的认识。方法对83例诊断明确、资料完整的AID合并肺动脉高压患者进行回顾性分析。结果5年间收治的2016例AID患者中合并肺动脉高压83例(4.1%),年龄10～67岁,平均(33±13)岁,其中男性7例(8.4%),女性76例(91.6%),占同期入院收治的肺动脉高压患者(350例)的31.1%。本组病例中易合并肺动脉高压的AID包括混合性结缔组织病(MCTD)、系统性硬化症(SSc),合并概率最低的为皮肌炎/多发性肌炎(DM/PM)。合并抗磷脂抗体综合征(APS)的系统性红斑狼疮(SLE)患者出现肺动脉高压的概率增加。合并肺动脉高压的AID患者出现雷诺现象的比例很高(P=0),二者存在相关性。出现雷诺现象的患者多有弥散性肺通气障碍,而且病情容易恶化。抗u1RNP阳性的AID患者出现肺动脉高压的可能明显升高(P=0)。结论肺动脉高压是一组以肺小动脉受累的疾病,AID是其常见合并疾病,其中MCTD、SSc合并肺动脉高压的概率最高,DM/PM合并的概率最低。合并APS可以增加SLE出现肺动脉高压的概率。对于出现雷诺现象、抗u1RNP的AID患者应警惕肺动脉高压的可能,早期行超声心动图及相关检查,早期诊断,以改善患者的预后。     

多发性肌炎/皮肌炎合并肺间质病变的临床特征和预后

目的 研究多发性肌炎(PM)和皮肌炎(DM)合并肺间质病变(ILD)的临床特点和预后.方法 回顾性分析107例PM/DM患者的临床资料,包括首发症状、临床表现、实验室检查、影像学资料、治疗及预后.结果 107例PM/DM患者合并ILD有28例,ILD发生率为26.2%.①合并ILD的首发症状为关节炎或关节痛者高于无ILD(P<0.05);合并ILD临床表现为关节炎或关节痛、发热、干咳气促者明显高于无ILD(P<0.05).②DM合并ILD患者大多有特异性皮疹,呼吸困难较重(P<0.05),而PM合并ILD患者肌痛、肌无力较重(P<0.05).③合并ILD的红细胞沉降率(ESR)和C反应蛋白(CRP)明显高于无ILD(P<0.05);DM-ILD组肌酶谱以羟丁酸脱氢酶(HBDH)、天冬氨酸转氨酶(AST)升高为主(P≤0.05),PM合并ILD患者肌酶谱以肌酸激酶(CK)和肌酸激酶同工酶(CK-MB)为主(P<0.05).④合并ILD的28例PM/DM患者经治疗,20例病情改善,8例重症7例均为DM合并ILD,5例治疗无效因Ⅰ型呼吸衰竭死亡(病死率占PM/DM合并ILD患者的17.9%).结论 ①首发症状为关节炎或关节痛,临床表现有关节炎或者关节痛、发热以及ESR和CRP高者易合并ILD;有特异性皮疹、AST升高的DM易合并ILD;肌酶以CK和CK-MB升高为主的PM易合并ILD.②DM合并ILD病情进展凶险,病死率高,预后不良.     

199例结缔组织疾病心血管损害的分析(摘要)

<正> 我们分析了近20年中我院收治的199例结缔组织病:其心血管发病情况如下:病种总例数心血管受累例数 %系统性红斑性狼疮(SLE) 121 76 60.3类风湿性关节炎(RA) 45 10 22皮肌炎+多发性肌炎(DM+PM) 24 16 6.4硬皮症(SD) 5 4 80结节性多动脉炎(PAN) 4 4 100心血管受损情况除 RA 外,余均较高。且多发现在病程的5年以内,SLE 则高峰在5     

影响系统性红斑狼疮患者骨质疏松的多因素分析

目的对系统性红斑狼疮(SLE)患者发生骨质疏松的影响因素进行多因素分析。方法用双能X线骨密度测量仪测量了74例女性SLE患者4个部位的骨密度,用聚合酶链反应限制性片段长度多态(PCR-RFLP)经典法检测了61例女性SLE患者的维生素D受体基因型。对SLE患者诸多影响骨密度的因素进行逐步回归分析。结果SLE患者4个部位的骨密度均明显低于健康对照组(P<0.01),骨质疏松的发生率为19.7%,明显高于健康对照组(9.6 %,P<0.05)。SLE患者的维生素D受体基因型分布以bb基因型为主,占88.5%。维生素D受体基因和SLE患者骨质疏松的发生没有明显的相关性。多因素逐步回归分析提示激素的每日用量是影响SLE患者各个测定部位骨密度的独立因素。结论SLE患者骨质疏松的发生率较正常人群明显增高,其骨质疏松的发生和维生素D受体基因型关系不明显。激素的每日用量是影响骨质疏松发生的重要因素。     

混合性结缔组织病的严重肺部病变

Sharp等(1972)报告25例混合性结缔组织病,它具有系统性红斑狼疮(SLE)、硬皮病和多发性肌炎等临床特征,实验室检查抗ENA抗体阳性,有肺脏受累。Harman等报告的28例混合性结缔组织病中23例(82%)有肺功能不全。用激素治疗的14例中12例肺功能及胸片恢复正常。本文报告5例混合性结缔组织病伴有严重进行性肺损伤病人,其中3例有组织学资料并将检查结果与SLE或硬皮病肺部改变进行比较,文中还报告了皮质激素及细胞毒药物对本组病例的疗效。混合性结缔组织病临床特征为多关节痛、两手弥漫性肿胀、雷诺氏现象、食道运动低下和炎症性肌     

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.     

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.     

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.