Significance of pericardial cytokines in giant cell myocarditis in rats--pathological comparison to viral myocarditis in mice

To investigate the precise disease progression in myocarditis, Lewis rats were injected with porcine cardiac myosin, and C3H/He mice were inoculated with coxsackievirus B3. Both were killed serially, and the hearts were stained with hematoxylin-eosin to compare their pathological characteristics. In viral myocarditis, viral replication in the myocardium resulted in myocardial necrosis with inflammation, and the lesions were distributed transmurally, as previously reported. On the other hand, in giant cell myocarditis, inflammatory lesions appeared at first around the capillaries in the epicardium, and thereafter spread transmurally. Pericardial effusion was noticed in all the rats with myocarditis in the fulminant stage. Levels of interleukin (IL) -1beta and IL-6 in the pericardial effusion were elevated compared with the serum cytokines at the peak of inflammation. However, interferon-gamma in both the pericardial effusion and serum was not elevated. The cause of the myocardial lesions that developed in rats with giant cell myocarditis may be some active inflammatory process via the pericardial effusion.     

Idiopathic giant cell myocarditis and cardiac sarcoidosis

Idiopathic giant cell myocarditis (GCM) and cardiac sarcoidosis (CS) are rare disorders that cause cardiomyopathy, often with ventricular arrhythmias or heart block. Infection, autoimmune processes, and genetics have all been implicated in the pathogenesis of these diseases, but the etiology for both diseases is likely a complex multifactorial process. Both GCM and CS are generally progressive despite treatment with standard heart failure and arrhythmia therapies. Making the diagnosis of GCM or CS on initial clinical presentation is possible in only a small percentage of patients, so myocardial tissue diagnosis is required. The use of multiple noninvasive imaging modalities may aid in diagnosis and assessment of response to treatment. Establishing the diagnosis of GCM or CS early is crucial, as tailored immunosuppressive treatment may significantly alter the clinical course of these patients. The prognosis of patients with GCM is poor, while the prognosis for patients with CS varies according to degree of left ventricular dysfunction.     

Response of recurrent giant cell myocarditis in a transplanted heart to intensive immunosuppression

A 35-year-old man developed giant cell myocarditis resulting in severe congestive cardiac failure. He needed urgent orthotopic cardiac transplantation despite maximal doses of inotropes and augmentation with an intra-aortic balloon pump. The patient presented with rhythm disturbances and echocardiographically diminished ventricular function at subsequent follow-up. Biopsies then taken revealed recurrence of myocarditis in the transplanted heart. Investigations revealed no obvious cause for the myocardial granulomas nor any evidence of systemic granulomatous disease. The patient received, in addition to maintenance cyclosporin A and azathioprine, high doses of corticosteroids which resulted in complete resolution of the inflammatory process and no recurrence has been detected to date. This case shows that giant cell myocarditis can recur in the transplanted heart despite routine immunosuppression with azathioprine and cyclosporin A and that additional treatment with high dose corticosteroids is effective in causing regression of the inflammatory process.     

转录因子KLF2和KLF4调控人血管内皮细胞血管稳态相关基因表达的特征

[目的] Krüppel样因子(KLF)2和4是与血管稳态密切相关的两个核心转录因子,具有抗炎、抗钙化、抗血栓等多重保护效应。本研究旨在在内皮细胞中阐明并验证KLF2和KLF4共同调控的血管稳态相关基因谱。[方法]使用腺病毒(Ad-KLF2或Ad-KLF4)及对照病毒(Ad-NC)处理人脐静脉内皮细胞(HUVEC)24 h后提取RNA并进行转录组测序分析。过表达KLF2和KLF4的测序结果与已报道的KLF2/KLF4双基因敲除鼠测序结果进行叠加。筛选出的差异表达基因通过实时荧光定量PCR在Ad-KLF2或Ad-KLF4处理的HUVEC以及在阿托伐他汀或白藜芦醇处理的HUVEC中进行验证。[结果]转录组学叠加发现,KLF2和KLF4上调的差异基因有256个,KEGG通路富集分析显示这些差异基因主要富集于肥厚型心肌病、扩张型心肌病、ECM-受体交互以及黏着斑、致心律失常性右心室心肌病等;KLF2和KLF4下调的差异基因有145个,KEGG通路富集分析显示这些差异基因主要富集于癌症中的microRNA、糖胺聚糖生物合成-硫酸软骨素/硫酸皮聚糖、矿物质吸收、p53信号通路以及氨基酸生物合成等。...     

Pernicious anemia and giant cell myocarditis. New association

The association of pernicious anemia, an autoimmune disease, with other immunologic disorders such as dermatitis herpetiformis, Hashimoto's thyroiditis, hypothyroidism, hyperthyroidism, vitiligo, adrenal insufficiency, adult-onset immunoglobulin deficiency, hypoparathyroidism, and possibly diabetes mellitus has been reported. The association of pernicious anemia with giant cell myocarditis, a rare fatal illness believed by some to represent an autoimmune abnormality occurring with other autoimmune diseases such as thymoma, systemic lupus erythematosus, dermatomyositis, thyrotoxicosis, Wegener's granulomatosis, and Sjogren's syndrome, is reported for the first time. A common underlying autoimmune abnormality is suggested.     

Strain difference in rats with experimental giant cell myocarditis

Immunogenetic mechanisms may be involved in the pathogenesis of myocarditis and dilated cardiomyopathy. The present study investigated the incidence, histopathology and histocompatibility characteristics of experimental giant cell myocarditis in various strains of rats. Experimental giant cell myocarditis was induced by immunization with porcine cardiac myosin in Lewis (RT-1(l)), Dahl (DIR/Eis) (RT-1(l)), Fisher (RT-1(lv 1)) rats, but not in Dahl (DIS/Eis) (RT-1(l)) or Brown Norway (RT-1(n)). Myocarditis was most severe in the Lewis rats and their heart weight/body weight ratio was significantly higher than that of control rats immunized with Freund's complete adjuvant alone. In conclusion, this study provides evidence that the expression and severity of experimental giant cell myocarditis may be determined mainly by genetic factors, including both major histocompatibility complex genes as well as other genes, which may be controlled by an immune mechanism.     

Late recurrence of fulminant myocarditis related to HSS/DRESS

Hypersensitivity Syndrome or Drug Reaction with Eosinophilia and Systemic Symptoms (HSS/DRESS) is a rare pharmacological hypersensitivity reaction that may include cardiac involvement, with high mortality and long-term heart failure.A 28-year-old woman, two months after the diagnosis of DRESS secondary to sulfasalazine, developed fulminant eosinophilic necrotizing myocarditis. After intensive multiorgan support, recovery and cardiac function normalization were observed. Eight months later presented a recurrence with fast progression to refractory cardiogenic shock and death.We alert to a rare and underdiagnosed pathology, with adverse prognosis, needing timely identification and treatment.     

Fatal giant cell myocarditis after resection of thymoma.

A case of fulminant, fatal myocarditis occurring 10 days after resection of a benign medullary thymoma is described. A rare association between thymoma and giant cell myocarditis is recognised, but fulminant presentation so soon after removal of thymoma has not previously been reported.     

Characteristics of the course of complicated myocarditis

Twenty one patients (15 males and 6 females, mean age, 35.0 +/- 1.6 years) with myocarditis combined with symptoms of Stages II-III circulatory failure were examined. This group of patients was identified as a high-risk group as to an unfavourable outcome of myocarditis. Within the follow-up from 3 to 36 months, all the patients died: the case of death was arrhythmia in 17 and circulatory failure in 4. The unfavourable prognosis of the disease was evidenced by high pulmonary capillary pressure and pulmonary end-diastolic pressure that exceeded 20 mm Hg the cardiac index that was less than 31/min.m-2. The ratio of left ventricular end-systolic and end-diastolic volumes to the left ventricular cross-shortening were important signs of the unfavourable prognosis, i.e. death of congestive circulatory failure. In addition to complications of myocarditis such as sudden ventricular fibrillation, progressive congestive circulatory failure and thromboembolism, there were more rare complications such as development of left ventricular aneurysms and damage to the endocardium as abacterial endocarditis.     

Various factors determining the fatal outcome in myocarditis

A study of 38 patients with infectious-allergic myocarditis included clinical laboratory investigation, echocardiography, catheterization of the right heart compartments and the pulmonary artery and endomyocardial biopsy. It has identified adverse factors contributing to fatal outcome: increased end-diastolic pressure in the pulmonary artery, low cardiac output, signs of macrofocal fibrosis and small ejection fraction.     

Characteristics of fracture and related factors in patients with rheumatoid arthritis

To examine the clinical features of vertebral and non-vertebral fractures in patients with rheumatoid arthritis (RA), including insufficiency fractures, and to assess the risk factors for fracture, we prospectively studied 209 outpatients with rheumatoid arthritis for 1 year. The age, gender, Steinbrocker’s functional class, glucocorticoid use, history of lower limb surgery, serum C-reactive protein (CRP), and use of bisphosphonates were evaluated. Examination for fractures was performed by radiography, computed tomography (CT), magnetic resonance imaging (MRI), and bone scanning. Thirty-three fractures occurred in 24 patients over the 1-year study period, and the incidence was 15.8 fractures per 100 patient-years. Fractures occurred at various sites. The majority (70%) was insufficiency fracture, and more than 50% caused ambulatory dysfunction. Radiographic findings were absent in 39% of the fractures at the onset of pain. The functional class and glucocorticoid dose were significantly associated with fracture development. This prospective study showed that the incidence of fractures, especially insufficiency fractures, was very high in patients with rheumatoid arthritis and that most of their fractures caused gait disturbance. Early intervention to prevent secondary osteoporosis is recommended to maintain the quality of life in patients with rheumatoid arthritis, especially those with functional impairment or undergoing glucocorticoid therapy.     

Characteristics of fracture and related factors in patients with rheumatoid arthritis

Abstract

To examine the clinical features of vertebral and non-vertebral fractures in patients with rheumatoid arthritis (RA), including insufficiency fractures, and to assess the risk factors for fracture, we prospectively studied 209 outpatients with rheumatoid arthritis for 1 year. The age, gender, Steinbrocker’s functional class, glucocorticoid use, history of lower limb surgery, serum C-reactive protein (CRP), and use of bisphosphonates were evaluated. Examination for fractures was performed by radiography, computed tomography (CT), magnetic resonance imaging (MRI), and bone scanning. Thirty-three fractures occurred in 24 patients over the 1-year study period, and the incidence was 15.8 fractures per 100 patient-years. Fractures occurred at various sites. The majority (70%) was insufficiency fracture, and more than 50% caused ambulatory dysfunction. Radiographic findings were absent in 39% of the fractures at the onset of pain. The functional class and glucocorticoid dose were significantly associated with fracture development. This prospective study showed that the incidence of fractures, especially insufficiency fractures, was very high in patients with rheumatoid arthritis and that most of their fractures caused gait disturbance. Early intervention to prevent secondary osteoporosis is recommended to maintain the quality of life in patients with rheumatoid arthritis, especially those with functional impairment or undergoing glucocorticoid therapy.     

Unusual echocardiographic features seen in a case of giant cell myocarditis

The case of an 18-year-old college football player with a recent history of streptococcal pharyngitis who was experiencing progressive disabling dyspnea on exertion with easy fatigability and lack of stamina, and was taken to the hospital after a syncopal episode is described. The patient was initially diagnosed with heart failure and treated accordingly. However, because of a fulminant clinical deterioration, an endomyocardial biopsy was recommended, which showed focal giant cell transformation consistent with giant cell myocarditis. Treatment with methylprednisolone and cyclosporine was promptly initiated. Several apical clots were noted during treatment, but the patient attained full recovery with treatment.     

去卵巢大鼠骨质疏松凋亡细胞及其相关因素观察

目的　探讨去卵巢大鼠骨细胞凋亡活性及其相关因素。方法　采用3′-OH末端DNA原位标记技术观察凋亡细胞活性;采用免疫组化SABC法观察bcl-2、Fas、转化生长因子（TGF）β1的表达情况。结果　去卵巢大鼠成骨细胞的凋亡细胞活性为（40.5±5.2）%,较假手术组(24.5±3.0)%与去卵巢+尼尔雌醇/左炔诺孕酮治疗组［OVX+N/L组,（26.4±2.9)%］明显增加,差异有显著性(P＜0.01);去卵巢大鼠破骨细胞的凋亡细胞活性为（8.4±1.2）%,明显低于假手术组(24.0±2.9)%与OVX+N/L组(26.5±3.1)%,差异具有显著性(P＜0.01)。3组成骨细胞与破骨细胞内bcl-2阳性表达率均较低,差异无显著性(P值均>0.05);去卵巢大鼠组成骨细胞内Fas(80.0%)高于假手术组（40.0%）和OVX+N/L组（40.0%）,而破骨细胞内Fas(20.0%)低于假手术组(70.0%)和OVX+N/L组(73.3%),后者差异有显著性(χ2=7.94,P＜0.05),OVX组成骨和破骨细胞内TGFβ1(分别为20.0%、0),均低于其他两组,前者差异有极显著意义(χ2=13.104,P＜0.01)。结论　去卵巢大鼠骨丢失主要是由于雌激素水平低下引起破骨细胞凋亡减少、成骨细胞凋亡活性增加致骨吸收功能明显增加而超过骨形成所致;TGFβ1的分泌可能需要雌激素的刺激,TGFβ1表达可能抑制成骨细胞凋亡,促进破骨细胞凋亡,Fas可能诱导破骨细胞凋亡。     

Related factors for the development of fulminant myocarditis in adults

正Objective To determine the early recognizable factors related to patients with fulminant myocarditis.Methods Medical records from 60 adult patients who were diagnosed with acute viral myocarditis from January2003 to September 2016 in our hospital were retrospectively reviewed,and divided into fulminant group(n=9)     

Characteristics of haemopoietic progenitor cells related to CD34 epitope class expression

Haemopoietic progenitor cells (HPCs) express the CD34 molecule, a heavily glycosylated transmembrane protein displaying three main classes of epitopes. The CD34 epitope class expression may vary between different subsets of HPCs. The aim of this study was to characterise the subsets of HPCs expressing CD34 class II and III epitopes. The cells were studied for coexpression of activation-, lineage- and adhesion-associated molecules, and their clonogenic ability and morphological features were examined. CD34+ HPCs expressing class III epitopes outnumbered those expressing class II. Class III expressing HPCs were enriched for CFU-GM and BFU-E and cells coexpressing CD13, CD33, c-kit and CD71 compared to class II expressing HPCs. CD34+ cells exclusively expressing class III epitopes uniformly displayed CD13 and CD33; they had a high clonogenic capacity and morphological characteristics of promyelocytes and myelocytes. The data show that class III epitopes are distributed more broadly on CD34+ HPCs than are class II epitopes, and that lack of class II epitopes is confined to CD34+ HPCs at a late stage of myeloid differentiation. The higher number of class III expressing HPCs coexpressing c-kit and CD71 suggests that these cells exhibit a higher proliferative or differential potential than do HPCs expressing class II epitopes.