扩张型心肌病的病因分析与针对性治疗

目的:探讨扩张型心肌病(DCM)的病因,观察针对抗心肌抗体采取免疫学治疗的临床疗效和预后。方法:对2001年1月～2005年12月入院治疗的DCM患者301例的病史、诊治过程、随访结果进行回顾性分析。结果:301例中病毒阳性185例(占61.46%),抗心肌抗体阳性207例(68.77%),病毒感染与抗心肌抗体具有显著相关性。随访时间0.6～5.5(2.1±1.6)年,抗心肌线粒体腺嘌呤核苷酸异位酶抗体(抗ANT抗体)阳性患者(A组)治疗后平均左室舒张末期内径(LVEDd)为(61.13±8.57)mm,LVEF为(42.65±11.45)%,平均心胸比(HTR)0.56±0.06;抗β1-肾上腺素能受体抗体(抗β1-受体抗体)阳性患者(B组)治疗后LVEDd(61.85±6.48)mm,LVEF(41.75±10.87)%,HTR0.56±0.02;抗ANT抗体和抗β1-受体抗体均阳性患者(C组)治疗后LVEDd(63.48±8.82)mm,LVEF(39.39±7.95)%,HTR0.57±0.08。3组与治疗前比较均差异有统计学意义(P<0.05)、NYHA心功能分级均改善Ⅰ～Ⅱ级。结论:病毒感染/自身免疫是DCM的常见致病因素,针对抗ANT抗体早期使用地尔硫和针对抗β1-受体抗体使用美托洛尔治疗DCM均可明显改善患者心脏功能,提高其生活质量。     

扩张型心肌病抗心肌线粒体ADP/ATP载体自身抗体与Th细胞亚群分析

目的 :探讨扩张型心肌病 (DCM)的体液免疫学发病机制。方法 :借助免疫转印技术及流式细胞仪技术同步分析了 33例 DCM患者和 2 8例正常人的血清中抗心肌线粒体 ADP/ATP载体自身抗体和 Th细胞亚群。结果 :DCM组 Th2 细胞在外周血淋巴细胞中占 (0 .5 3± 0 .2 3) % ,对照组 Th2 细胞占 (0 .2 2± 0 .18) % ,两组比较差异有显著性 (P <0 .0 1) ;DCM组抗心肌线粒体 ADP/ATP载体抗体的检出率 (6 0 .6 1% )明显高于对照组(2 1.43% ) (P <0 .0 1) ;DCM抗心肌线粒体 ADP/ATP载体自身抗体 ,阳性组中 Th2 细胞在外周血淋巴细胞中占 (0 .6 7± 0 .31) % ,阴性组 Th2 细胞占 (0 .2 8± 0 .14) % ,两组比较差异有显著性 (P<0 .0 1)。结论 :DCM中 Th2细胞与抗心肌线粒体 ADP/ATP载体自身抗体的产生有关 ,而且 Th2 细胞和抗心肌线粒体 ADP/ATP载体自身抗体参与了 DCM的病理过程。体液免疫反应的异常在 DCM的发病机制中起着十分重要的作用。     

肠病毒感染及抗ADP/ATP载体抗体在病毒性心脏病发病中的意义

目的 :探讨肠病毒感染与抗二磷酸腺苷 /三磷酸腺苷 (ADP/ ATP)载体抗体在病毒性心脏病发病中的意义。方法 :应用逆转录聚合酶链式反应 (RT- PCR)和免疫转印法对临床诊断为病毒性心肌炎 (VMC)和扩张型心肌病 (DCM)患者进行肠病毒核糖核酸 (RNA)及抗 ADP/ ATP载体抗体的检测。结果 :RT- PCR方法检测肠病毒 RNA,VMC组 (n =74) 4 2例 (56.8% )阳性 ,DCM组 (n=2 6) 1 1例 (42 .3% )阳性。与健康组 (n =30 )比较具有显著性差异 (分别 P <0 .0 1 ,P <0 .0 5) ;肠病毒感染与 DCM患者心脏功能降低有明显相关性。免疫转印法检测 VMC(n =34)和 DCM(n =2 6)患者血清抗 ADP/ ATP载体抗体 ,VMC组 2 3例 (67.6% )阳性 ,DCM组 1 2例 (46.2 % )阳性 ,而健康组均为阴性 ;抗 ADP/ ATP载体抗体和肠病毒 RNA的检出相关 (r=0 .442 )。结论 :肠病毒RNA和抗 ADP/ ATP载体抗体在病毒性心脏病患者中检出具有相关性 ,对临床上出现前驱感染和心脏症状的患者 ,及时进行肠病毒 RNA、CVB- Ig M、抗 ADP/ ATP载体抗体的检测 ,有助于 VMC和 DCM的早期诊断。     

系列抗心肌多肽自身抗体对扩张型心肌病的诊断价值

目的 :探讨抗人工合成多肽自身抗体在扩张型心肌病 ( DCM)诊断中的价值。方法 :根据计算机预测心肌 ADP/ ATP载体 ( ANT)、β1 受体、M2 受体和肌球蛋白重链 ( MHC)抗原决定簇的氨基酸序列并合成多肽片段 ,以此片段作为抗原 ,同时用天然抗原对比 ,以酶联免疫吸附方法检测 48例 DCM患者 ( DCM组 )和 48例健康献血员 (对照组 )血清中抗心肌多肽自身抗体。结果 :DCM组中抗 ANT抗体、抗 β1 受体抗体、抗 M2 受体抗体和抗MHC抗体阳性分别有 31、2 6、2 0和 2 3例 ,与对照组比较有显著性差异 ( P <0 .0 0 5 ) ,且与天然心肌抗原检测结果高度一致 ( P <0 .0 1)。结论 :人工合成多肽可代替天然心肌抗原用于检测抗心肌自身抗体 ,抗心肌多肽抗体检测可以作为 DCM免疫学诊断方法     

扩张型心肌病的早期干预

扩张型心肌病 ( DCM)的主要病因是病毒持续感染和自身免疫反应。在 DCM早期可以检测出抗心肌自身抗体 ,抗体介导心肌细胞损伤机制已基本阐明 ,阻止抗心肌抗体介导心肌损伤已成为早期治疗 DCM的有效方法之一。根据分子模仿理论 ,发现 ADP/ ATP载体蛋白与柯萨奇 B3 -病毒外壳蛋白存在同源性 ,酶联免疫吸附试验证实抗 ADP/ ATP载体 2 7- 36肽抗体可以与来源于柯萨奇 B3 病毒 1 2 1 8- 1 2 2 8肽发生免疫反应 ;鼠肝炎病毒、人类巨细胞病毒与 β1-肾上腺素能受体之间具有相同的抗原决定簇 ,还发现抗ADP/ ATP载体抗体可以与钙通道蛋白…     

抗心肌抗体消长与病毒性心脏病转化关系探讨

目的:探讨抗心肌抗体消长与病毒性心脏病(VHD)病程的关系及在病毒性心肌炎(VMC)向扩张型心肌病(DCM)转化过程中所起的作用。方法:通过计算机预测ADP/ATP载体(ANT)、β1-受体、M2-胆碱能受体及肌球蛋白重链(MHC)抗原决定簇的氨基酸序列,用人工多肽合成仪合成的多肽作为抗原,应用ELISA方法,对不同病程的VHD患者进行抗心肌抗体的检测,同时对慢性VMC(CVMC)患者进行追踪观察及干预,并评价疗效。结果:随着VHD患者病程的延长,4种抗心肌抗体的检出率呈先升高后降低的趋势,CVMC和早期DCM患者抗心肌抗体阳性率最高;22例抗体阳性的CVMC患者经过3.1年随访,其中8例演变成为DCM,经给予相应药物干预治疗后6例恢复正常;而6例抗体阴性的患者随访期间均未出现DCM表现。结论:监测患者血清中抗心肌抗体有助于防止VMC向DCM转化,对DCM的早期诊断和干预及VHD的疗效判断和预后都可以提供重要的线索。     

大剂量丙种球蛋白对扩张型心肌病心衰患者心肌肌凝蛋白重链自身IgG抗体滴度的影响

目的:探究大剂量丙种球蛋白对扩张型心肌病(DCM)心力衰竭患者心肌肌凝蛋白重链(CMHC)自身免疫球蛋白G(IgG)抗体滴度和临床疗效的影响。方法:选择2011年3月~2014年5月我院心内科收治的DCM心力衰竭患者160例。按照随机数字表法,患者被随机均分分为常规治疗组(80例)和丙种球蛋白组(80例,在常规治疗组基础上接受大剂量丙种球蛋白治疗)。观察比较两组患者治疗前后的心功能指标,IgG抗体滴度以及血清心肌肌钙蛋白T(cTnT)和cTnI水平。结果:与治疗前比较,治疗6个月后丙种球蛋白组左室舒张末期内径[LVEDd,(67.50±5.50)mm比(56.50±2.50)mm]和左室收缩末期内径[LVESd,(55.50±6.80)mm比(43.50±2.30)mm]显著降低,左室射血分数[LVEF,(33.50±3.50)%比(53.50±8.50)%]显著升高,而常规治疗组仅LVEF[(32.80±4.20)%比(41.50±5.50)%]显著升高,P均0.05;与常规治疗组比较,治疗6个月后丙种球蛋白组的LVEDd[(63.50±2.50)mm比(56.50±2.50)mm]和LVESd[(51.60±4.80)mm比(43.50±2.30)mm]显著降低,LVEF显著升高,P均0.05。治疗1、3、5和6个月后,丙种球蛋白组IgG抗体滴度显著降低,且均显著低于同期常规治疗组的(P均0.05)。治疗6个月后两组cTnT和cTnI水平均较治疗前显著减低(P均0.05),且与常规治疗组比较,丙种球蛋白组cTnT[(0.55±0.10)μg/L比(0.26±0.02)μg/L]和cTnI水平[(1.20±0.40)μg/L比(0.60±0.10)μg/L]下降更显著(P均0.05)。结论:大剂量丙种球蛋白治疗扩张型心肌病心力衰竭患者,能够显著改善患者的心肌功能,明显降低心肌肌凝蛋白重链自身IgG抗体水平,显著降低血清肌钙蛋白T和I的含量,值得在临床上推广。     

地尔硫卓对老年扩张型心肌病患者血清microRNA表达的调控

目的:探讨盐酸地尔硫卓缓释片对老年扩张型心肌病(DCM)患者血清microRNA表达的影响。方法:选择120例老年DCM患者为DCM组,60例身体健康的老年人为正常对照组。DCM组被进一步随机均分为常规治疗组(60例,接受常规治疗)和地尔硫卓组(60例,在常规治疗基础上加用盐酸地尔硫卓缓释片)。观察比较常规治疗组和地尔硫卓组治疗前后左室舒张末期内径(LVEDd)、左室后壁厚度(LVPWT)和左室射血分数(LVEF),以及治疗后两组心功能改善情况,比较三组治疗前,治疗后6周和12周时血清miR-1,-133,-499和-208表达量的变化。结果:与治疗前比较,常规治疗组治疗后LVEDd、LVPWT和LVEF无显著变化(P均0.05);地尔硫卓组LVEDd[(69.41±6.42)mm比(61.32±5.31)mm]和LVPWT[(20.98±1.98)mm比(12.05±2.42)mm]均显著降低,且显著低于常规治疗组[LVEDd:(67.25±4.21)mm,LVPWT:(18.49±2.86)mm],LVEF[(32.81±4.71)%比(50.52±6.88)%]显著升高,且显著高于常规治疗组[(47.77±3.92)%],P均0.05。心功能改善:地尔硫卓组的显效率(71.7%比56.7%)和总有效率(98.3%比85.0%)显著高于常规治疗组,P均0.05。DCM常规治疗组的4种miR表达量较正常对照组显著下降,而地尔硫卓组的miR表达量较常规治疗组有显著上升(P均0.01),但与治疗6周时比较,治疗12周时有下降趋势以miR-208最显著(P0.01)结论:地尔硫卓可有效调控老年扩张型心肌病患者血清中microRNA的表达,为研究地尔硫卓的作用机制提供了分子生物学依据。     

不同时期应用抗L3T4单抗治疗的自身免疫性心肌病小鼠免疫球蛋白G亚型分析

目的:探讨不同阶段应用抗L3T4单抗治疗自身免疫性心肌病对小鼠血清抗线粒体ADP/ATP载体抗体和免疫球蛋白G(IgG)亚型的影响。方法:将24只小鼠随机分为4组,每组6只。用含有人线粒体ADP/ATP载体肽的免疫液免疫近交系Balb/C小鼠建立类扩张型心肌病(DCM)模型(DCM组);以不含肽免疫液免疫小鼠作为对照组;在同时用含有ADP/ATP载体肽的免疫液的第0、1、2天连续3d以400μg抗L3T4单抗免疫小鼠获得早期治疗组;在给予ADP/ATP载体肽的免疫液第4个月初始连续3d给予抗L3T4单抗治疗获得中期治疗组。以ELISA法检测其血清中抗ADP/ATP载体抗体水平和IgG亚型(IgG1、IgG2a、IgG2b和IgG3)的变化;采用流式细胞术检测小鼠脾脏中CD4 T细胞内γ干扰素(IFN-γ)/白细胞介素(IL)-4的表达。结果:早期治疗组与对照组小鼠抗ADP/ATP载体抗体检测均为阴性,而中期治疗组与DCM组抗体均为阳性。DCM组各亚类水平均较对照组明显升高;早期治疗组IgG1、IgG2b和IgG3的产生均受到抑制,其水平接近对照组;中期治疗组IgG1水平介于DCM组和早期治疗组之间,IgG2b和IgG3的生成与DCM组差异无统计学意义,但显著高于早期治疗组;而治疗组与DCM组IgG2a水平则差异无统计学意义。早期治疗组小鼠IFN-γ/IL-4百分含量与对照组相比差异无统计学意义,但明显低于DCM组;中期治疗组IFN-γ的百分含量较DCM组更高,IL-4的百分含量介于DCM组和早期治疗组之间。结论:抗L3T4单抗治疗能够抑制DCM小鼠血清中的抗ADP/ATP载体抗体及IgG1亚型的生成和Th2相关细胞因子IL-4的百分含量,且以早期治疗的效果更明显。     

扩张型心肌病与心肌自身抗体的研究进展

近年来,随着免疫学、病毒学、分子生物学理论与技术的发展,抗心肌抗体与扩张型心肌病（DCM）的关系越来越受重视。抗心肌抗体的产生和参与DCM的资料累积已近50年。例如抗β肾上腺能受体抗体、抗ATP/ADP运载蛋白抗体、抗M胆碱能受体抗体和抗肌球蛋白重链抗体等,均可激活机体免疫系统使心肌细胞肿胀和坏死,是心脏受累的重要指标。本文主要对DCM与心肌自身抗体的相关发病机制作一综述。     

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.